The iris forms the anterior part of the uveal tract, which represents the middle of the three coats of the globe.
As with the other parts of the tract, such as the ciliary body (discussed in Part 5, optician, April 30) and choroid, the iris is characterised by dense pigmentation and possesses a rich blood supply. Smooth muscle is also present to facilitate pupil dynamics.
The iris
The iris is a thin muscular diaphragm, continuous with the ciliary body and separating the anterior and posterior chambers of the eye.
The central aperture, the pupil, can vary in diameter from about 2mm to 8mm under natural conditions, governed by the actions of two smooth muscles, the sphincter and dilator pupillae (Figure 1).
The efficiency of the iris as a light stop, which is its principal function, is due to its dense pigmentation. Stromal pigment contributes to this property, but the amount is variable and the pigment epithelium on the posterior surface of the iris has primary responsibility for ensuring that light enters the eye only through the pupil. A change in pupil diameter from 2mm to 8mm represents a 16-fold increase in area. This variation in size ensures that the amount of light entering the eye is maintained within an optimal operating range by admitting more light when the ambient illumination is dim and admitting less light when the ambient illumination is bright.1
Gross appearance
The iris is approximately 12mm in diameter and 38mm in circumference. It is thickest at the collarette, an irregularly scalloped structure roughly concentric with the pupil margin (Figure 2) and thinnest at its root (0.2mm) where it attaches to the ciliary body.
The collarette overlies an incomplete vascular circle (minor iridic circle), and marks the boundary between the ciliary and pupillary zones of the iris. The ciliary zone is much the larger part of the surface of the iris, and extends from the collarette to the attachment of the iris at the ciliary body. The ciliary zone shows considerable variation in appearance due to the presence of folds, furrows, and crypts (of Fuchs) of varying size and shape. Crypts are absent or infrequent in darker races and the iris has a regular velvety texture.
In such cases, two or more peripheral circumferential folds typically disturb the regular surface. The pupillary zone has slight radial thickenings reflecting the pattern of underlying blood vessels. In a grey or blue iris, the sphincter pupillae is often visible encircling the pupil. At the pupil margin the posterior layers of the iris extend forward to form a pupillary ruff.
The posterior surface of the iris has a regular deep brown colour marked by ridges or striae converging to the iris margin, with a superimposed pattern of shallow, frequent, regularly spaced circumferential grooves. With the iris normally resting on the anterior surface of the crystalline lens, the radial ridges facilitate flow of aqueous humour from the posterior to the anterior chamber.
When the iris stroma is thin and sparsely pigmented, shorter wavelengths are selectively scattered back to the observer and the longer wavelengths penetrate to the pigmented posterior epithelial layers and are absorbed. Consequently the iris appears blue. Otherwise, melanin pigment within melanocytes is responsible for iris colour. Cells containing sparse pigment granules (melanosomes) will produce a grey colour and with increasing concentration, the colour produced is mid-brown, then dark brown. So, in the heavily pigmented iris, with a thick regular stroma, the colour is uniformly mid to dark brown and, in the less heavily pigmented iris, one or more of the colour varieties is expressed.
Often, in an otherwise poorly pigmented iris, brown freckles are present; where local clusters of anterior border layer melanocytes occur. Slight congenital difference in the colour pattern between irises of the same individual (heterochromia) is quite common. By contrast, acquired heterochromia may be drug-induced, or the result of nerve injury or neoplasia.
Histology
From the posterior surface forward, the layers of the iris are (Figure 3):
1) Posterior pigment epithelium
2) Anterior epithelium and dilator pupillae muscle
3) Substantia propria (stroma) including the sphincter pupillae muscle and the blood vessels
4) Anterior border layer.
Posterior pigment epithelium
The posterior pigment epithelium consists of melanin-rich columnar cells mounted on a thin basement membrane (Figures 4 and 5). Shallow infoldings are numerous at the basal aspect of each cell and finger-like processes extend from the lateral walls making contact with those of the neighbouring cells.
Scattered desmosomes, intermediate junctions and less numerous gap junctions link apposed walls. Adjacent cells are also joined by tight junctions at their apices.2 As well as the barrier property of tight junctions, this impressive connectivity ensures the layer's capacity to withstand the vigorous excursions of the iris. At the iris margin the posterior epithelium curls forward slightly, forming the ruff at the pupil margin.
Anterior epithelium and dilator pupillae
The anterior epithelium forms a thinner, rather less heavily pigmented layer. The anterior epithelium has two morphologically distinct portions: an apical 'epithelial' portion and a basal 'muscular' portion. The apical portion is directed towards the posterior epithelium, to which it forms frequent desmosomes and gap junction attachments.3
Lengthy, smooth muscle processes arise from the basal portion of the cell, forming the specialised dilator pupillae (Figures 4 and 5).
Muscle processes immediately turn into the plane of the iris and pass radially towards the pupil margin, producing a thin sheet of smooth muscle covering the apical portion of the epithelium. The thickness of this muscle layer varies according to the state of contraction of the iris and, when strongly contracted, several rows of muscle processes are stacked together. A basement membrane covers the muscular processes except where they are in direct apposition. In these positions, they are joined by very numerous gap junctions and infrequent desmosomes.
The dilator muscle is richly innervated by sympathetic and infrequently by parasympathetic nerve fibre terminals.4,5 Sympathetic activation induces contraction of the muscle, dilating the pupil. The dilator terminates well short of the iris margin but overlaps the outer margin of the sphincter pupillae, to which it is linked by widely spaced, slender muscle strands.
Sphincter pupillae
By light microscopy the sphincter pupillae is visible as a ribbon-like band in the posterior stroma encircling the pupillary margin (Figure 3). It is separated from the anterior epithelium, from which it is embryologically derived, by a thin sheet of connective tissue.3 The smooth muscle fibres are spindle-shaped with their axes disposed circumferentially, forming a 1mm band in the plane of the iris with a thickness of 6-10 cells, varying with the state of contraction. The cells are packed with myofilaments and numerous mitochondria with aggregations at each pole of the fusiform nucleus. Bundles of muscle fibres are partially separated from their neighbours by incomplete thin connective tissue cell partitions. Fibres within bundles, and those in apposition where bundles meet, are joined by gap junctions and desmosomes. The impressive mobility of the sphincter, required to govern pupil size, demands a substantial rearrangement of its muscle fibres.
This cannot be achieved by fibre shortening alone and fibre bundles must also overlap, producing a large increment in muscle thickness when fully contracted. Melanosomes are sometimes present in muscle fibres, indicating their pigment epithelial origin. Myelinated parasympathetic nerve fibres from the oculomotor nerve lose their myelin and terminate in the muscle. Many of the terminals lie at the perimeter of the muscle but others penetrate between the bundles with a similar relationship with muscle fibres as in the dilator. A few sympathetic nerve fibres also terminate in the sphincter muscle.4,5
Stroma (Substantia propria)
The stroma is composed of a loose network of connective tissue (Figure 4). Practically all fibrous material is collagen (type VI) set in a glycoprotein matrix and organised in a series of meshes orientated parallel to the surface, with the stronger strands directed radially.6
Cellular elements of the stroma include: fibroblasts, melanocytes, clump cells and mast cells. Fibroblasts are the most numerous of the stromal cells. These spindle-shaped cells often congregate around blood vessels, nerves and muscle fibres, where they often co-localise with melanocytes. Melanocytes possess a round or oval cell body, from which numerous long branching processes arise. Pigment granules (melanosomes) are found within their cytoplasm. However, the frequency and size of melanosomes is highly variable between individuals and often between cells of the same iris. Clump cells are large phagocytic cells (up to 100 microns in diameter) containing lysosomes and ingested melanosomes. They are most numerous in the pupillary zone and their number increases with age.
Anterior border layer
The anterior border layer represents a modification of the stroma. Its thickness is variable, being thickest in the pupillary zone and thinned at contraction folds and absent at crypts.
The density and thickness of the border layer also varies with age and iris colour.7 Electron microscopy reveals that the anterior border layer is composed of two types of cell: melanocytes and fibroblasts (Figure 6). A discontinuous layer of fibroblasts overlies a dense aggregation of pigmented melanocytes.3
The anterior border layer is the principal determinant of iris colour: it is thin in a blue iris and thick and densely pigmented in brown irises. Local accumulations of densely pigmented melanocytes give rise to iris freckles, commonly seen in the lighter iris. Darkening of the iris is a commonly reported adverse reaction to topical prostaglandin analogues, used in the treatment of glaucoma. Morphological investigations have shown that the induced colour change results from an increased size of melanosomes within melanocytes of the anterior border layer.8
Blood supply
Arterioles pass radially from the major iridic circle in the ciliary body and form two fine vascular circles, the minor iridic circle at the collarette and the marginal arcades.
The minor iridic circle is incomplete, consisting of a series of irregular loops,9 whereas the marginal arcades form an unbroken necklace of vessels of similar lumen. Both are drained by venules that also pass radially to the ciliary body. The anterior stroma of the ciliary zone has a loose mesh of randomly orientated capillaries. A deeper, denser capillary meshwork is related to the muscles of the iris. The vessel form is adapted to the extensive motion of the iris. The vascular circles are irregular and undulating, with plenty of slack, so that when the iris undergoes contraction they are able to expand their diameters with facility. The radial vessels tend to spiral during iris contraction reducing the possibility of kinking and so maintaining vessel patency.
Vessel walls consist of unfenestrated endothelial cells, covered by pericytes and a thick fibrous adventitia. The adventitia contains fibroblasts, with long, thin processes, in a sheath of connective tissue composed of a thick, tightly-woven network of collagen fibrils. Melanocytes and tiny bundles of unmyelinated nerve fibres are occasionally present in this layer, and it may also contain macrophages and other inflammatory cells. This structure is common to all iris vessels, with a thickness usually consistent with the size of the vessel.
Whether or not the nerve fibres are true vascular terminals or merely passing to the muscles is uncertain. At the root of the iris, typical smooth muscle cells are present in the walls of the arterioles but shortly after entry into the iris they thin considerably and have the characteristic structure of pericytes.
The narrow clefts between vascular endothelial cells are closed by continuous tight junctions,10 which imparts a barrier property to these vessels (Figure 7). This barrier function contributes to the integrity of the blood-aqueous barrier that maintains a low protein concentration within the aqueous humour.
Innervation
Many small, myelinated and unmyelinated nerve fibres, parasympathetic and sympathetic respectively, enter the iris from the ciliary body plexuses of nerves.
They enter the iris radially as small discrete bundles, yet lacking a perineurium. The bundles divide as they progress through the stroma and myelin is lost well before the fibres terminate in the dilator and sphincter muscles. Some of the sympathetic fibre terminals contact melanocytes, mainly adjacent to the dilator pupillae and in the anterior border layer.5
There is tangible evidence that sympathetic terminals regulate melanin synthesis11 yet, despite considerable attention, the mechanism remains poorly understood. A link between cervical sympathetic injury and iris colour has long been known12 and in children it leads to heterochromia, whereas in adults a similar response is disputed and it appears that if the condition occurs in adults it is usually slight and slow to develop.
Trigeminal sensory fibres are present in the iris. Their number is small in man13 and their distribution is uncertain. Most of our knowledge stems from observations of substance-P-containing neurons, presumed to be sensory, but the low density in primates has also been demonstrated in degeneration studies.14 The discomfort evoked by iris stimulation, for example during laser iridotomy,15 may be attributed to stimulation of sensory endings in the iris or in the ciliary body plexus at the root of the iris.
References
1 Oyster CW The human eye. Structure and function. 1999. Sinauer Associates, Inc.
2 Freddo TF. Intercellular junctions of the iris epithelia in Mucaca mulatta. Invest Ophthalmol Vis Sci,1984; 25, 1094-1104.
3 Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. 1971. WB Saunders Company.
4 Kern R. Adrenergischen Receptoren der intraocularen Muskeln des Menschen. Ein in vitro Studie. Graefes Arch klin exptl Ophthalmol, 1970;180, 231-248.
5 Ehinger B. A comparative study of the adrenergic nerves to the anterior eye segment of some primates. Z Zellforsch, 1971; 116, 157-177.
6 van der Zypen E. The arrangement of the connective tissue in the stroma iridis of monkey and man. Exp Eye Res, 1978; 27, 349-358.
7 Okamura R, Lutjen-Drecoll E. Elektronen mikroskopische Untersuchungen uber die Altersveranderungen der menschlichen Iris. Graefes Arch klin exp Ophthalmol, 1973; 186, 249-269
8 Cracknell KP, Grierson I, Hogg P, Appleton P, Pfeiffer N. Latanoprost-induced iris darkening: a morphological study of human periperal iridectomies. Exp Eye Res, 2003; 77, 721-30.
9 Shimizu K, Ujiie K. Structure of Ocular Vessels. 1978.Tokyo, Igaku-shoin.
10 Vegge T, Ringvold A. Ultrastructure of the wall of human iris vessels. Z Zellforsch, 1969; 94, 19-31.
11 Laties AM. Ocular melanin and the adrenergic innervation of the eye. Trans Am Ophthalmol Soc, 1974; 72, 560-605.
12 Calhoun FP. Causes of heterochromia irides with special reference to paralysis of the cervical sympathetic. Am J Ophthalmol, 1919; 2, 255-269.
13 Tervo T, Tarkkanen A, Tervo K. Innervation of the human pupillary sphincter by nerve fibers immunoreactive to substance P. Ophthal Res, 1985; 17, 111-114.
14 Bergmanson JPG. The ophthalmic innervation of the uvea in monkeys. Exp Eye Res, 1977; 24, 225-240.
15 Perkins ES, Brown NAP. Iridotomy with a ruby laser. Br J Ophthalmol, 1973; 57, 487-498.
16 Lissen A, Rothova A, Valkenburg HA, Dekker-Saeys AJ, Luyendijk L, Kijlstra A, Feltkamp TE. The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to alkylosing spondylitis and histocompatability antigen HLA-B27. Invest Ophthalmoml Vis Sci,1991; 32, 2568-78.
17 Hogan MH, Kimura SJ, Tygeson, P. Signs and symptoms of uveitis I: Anterior uveitis. Am J Ophthalmol, 1959; 47, 155-70.
18 Campbell DG, Schetzer RM. Pathophysiology of pigment dispersion syndrome and pigmentary glaucoma. Curr Opin Ophthalmol, 1995; 6, 96-101.
Professor John Lawrenson works in the Department of Optometry and Visual Science at City UniversityThe iris forms the anterior part of the uveal tract, which represents the middle of the three coats of the globe.
As with the other parts of the tract, such as the ciliary body (discussed in Part 5, optician, April 30) and choroid, the iris is characterised by dense pigmentation and possesses a rich blood supply. Smooth muscle is also present to facilitate pupil dynamics.
The iris
The iris is a thin muscular diaphragm, continuous with the ciliary body and separating the anterior and posterior chambers of the eye.
The central aperture, the pupil, can vary in diameter from about 2mm to 8mm under natural conditions, governed by the actions of two smooth muscles, the sphincter and dilator pupillae (Figure 1).
The efficiency of the iris as a light stop, which is its principal function, is due to its dense pigmentation. Stromal pigment contributes to this property, but the amount is variable and the pigment epithelium on the posterior surface of the iris has primary responsibility for ensuring that light enters the eye only through the pupil. A change in pupil diameter from 2mm to 8mm represents a 16-fold increase in area. This variation in size ensures that the amount of light entering the eye is maintained within an optimal operating range by admitting more light when the ambient illumination is dim and admitting less light when the ambient illumination is bright.1
Gross appearance
The iris is approximately 12mm in diameter and 38mm in circumference. It is thickest at the collarette, an irregularly scalloped structure roughly concentric with the pupil margin (Figure 2) and thinnest at its root (0.2mm) where it attaches to the ciliary body.
The collarette overlies an incomplete vascular circle (minor iridic circle), and marks the boundary between the ciliary and pupillary zones of the iris. The ciliary zone is much the larger part of the surface of the iris, and extends from the collarette to the attachment of the iris at the ciliary body. The ciliary zone shows considerable variation in appearance due to the presence of folds, furrows, and crypts (of Fuchs) of varying size and shape. Crypts are absent or infrequent in darker races and the iris has a regular velvety texture.
In such cases, two or more peripheral circumferential folds typically disturb the regular surface. The pupillary zone has slight radial thickenings reflecting the pattern of underlying blood vessels. In a grey or blue iris, the sphincter pupillae is often visible encircling the pupil. At the pupil margin the posterior layers of the iris extend forward to form a pupillary ruff.
The posterior surface of the iris has a regular deep brown colour marked by ridges or striae converging to the iris margin, with a superimposed pattern of shallow, frequent, regularly spaced circumferential grooves. With the iris normally resting on the anterior surface of the crystalline lens, the radial ridges facilitate flow of aqueous humour from the posterior to the anterior chamber.
When the iris stroma is thin and sparsely pigmented, shorter wavelengths are selectively scattered back to the observer and the longer wavelengths penetrate to the pigmented posterior epithelial layers and are absorbed. Consequently the iris appears blue. Otherwise, melanin pigment within melanocytes is responsible for iris colour. Cells containing sparse pigment granules (melanosomes) will produce a grey colour and with increasing concentration, the colour produced is mid-brown, then dark brown. So, in the heavily pigmented iris, with a thick regular stroma, the colour is uniformly mid to dark brown and, in the less heavily pigmented iris, one or more of the colour varieties is expressed.
Often, in an otherwise poorly pigmented iris, brown freckles are present; where local clusters of anterior border layer melanocytes occur. Slight congenital difference in the colour pattern between irises of the same individual (heterochromia) is quite common. By contrast, acquired heterochromia may be drug-induced, or the result of nerve injury or neoplasia.
Histology
From the posterior surface forward, the layers of the iris are (Figure 3):
1) Posterior pigment epithelium
2) Anterior epithelium and dilator pupillae muscle
3) Substantia propria (stroma) including the sphincter pupillae muscle and the blood vessels
4) Anterior border layer.
Posterior pigment epithelium
The posterior pigment epithelium consists of melanin-rich columnar cells mounted on a thin basement membrane (Figures 4 and 5). Shallow infoldings are numerous at the basal aspect of each cell and finger-like processes extend from the lateral walls making contact with those of the neighbouring cells.
Scattered desmosomes, intermediate junctions and less numerous gap junctions link apposed walls. Adjacent cells are also joined by tight junctions at their apices.2 As well as the barrier property of tight junctions, this impressive connectivity ensures the layer's capacity to withstand the vigorous excursions of the iris. At the iris margin the posterior epithelium curls forward slightly, forming the ruff at the pupil margin.
Anterior epithelium and dilator pupillae
The anterior epithelium forms a thinner, rather less heavily pigmented layer. The anterior epithelium has two morphologically distinct portions: an apical 'epithelial' portion and a basal 'muscular' portion. The apical portion is directed towards the posterior epithelium, to which it forms frequent desmosomes and gap junction attachments.3
Lengthy, smooth muscle processes arise from the basal portion of the cell, forming the specialised dilator pupillae (Figures 4 and 5).
Muscle processes immediately turn into the plane of the iris and pass radially towards the pupil margin, producing a thin sheet of smooth muscle covering the apical portion of the epithelium. The thickness of this muscle layer varies according to the state of contraction of the iris and, when strongly contracted, several rows of muscle processes are stacked together. A basement membrane covers the muscular processes except where they are in direct apposition. In these positions, they are joined by very numerous gap junctions and infrequent desmosomes.
The dilator muscle is richly innervated by sympathetic and infrequently by parasympathetic nerve fibre terminals.4,5 Sympathetic activation induces contraction of the muscle, dilating the pupil. The dilator terminates well short of the iris margin but overlaps the outer margin of the sphincter pupillae, to which it is linked by widely spaced, slender muscle strands.
Sphincter pupillae
By light microscopy the sphincter pupillae is visible as a ribbon-like band in the posterior stroma encircling the pupillary margin (Figure 3). It is separated from the anterior epithelium, from which it is embryologically derived, by a thin sheet of connective tissue.3 The smooth muscle fibres are spindle-shaped with their axes disposed circumferentially, forming a 1mm band in the plane of the iris with a thickness of 6-10 cells, varying with the state of contraction. The cells are packed with myofilaments and numerous mitochondria with aggregations at each pole of the fusiform nucleus. Bundles of muscle fibres are partially separated from their neighbours by incomplete thin connective tissue cell partitions. Fibres within bundles, and those in apposition where bundles meet, are joined by gap junctions and desmosomes. The impressive mobility of the sphincter, required to govern pupil size, demands a substantial rearrangement of its muscle fibres.
This cannot be achieved by fibre shortening alone and fibre bundles must also overlap, producing a large increment in muscle thickness when fully contracted. Melanosomes are sometimes present in muscle fibres, indicating their pigment epithelial origin. Myelinated parasympathetic nerve fibres from the oculomotor nerve lose their myelin and terminate in the muscle. Many of the terminals lie at the perimeter of the muscle but others penetrate between the bundles with a similar relationship with muscle fibres as in the dilator. A few sympathetic nerve fibres also terminate in the sphincter muscle.4,5
Stroma (Substantia propria)
The stroma is composed of a loose network of connective tissue (Figure 4). Practically all fibrous material is collagen (type VI) set in a glycoprotein matrix and organised in a series of meshes orientated parallel to the surface, with the stronger strands directed radially.6
Cellular elements of the stroma include: fibroblasts, melanocytes, clump cells and mast cells. Fibroblasts are the most numerous of the stromal cells. These spindle-shaped cells often congregate around blood vessels, nerves and muscle fibres, where they often co-localise with melanocytes. Melanocytes possess a round or oval cell body, from which numerous long branching processes arise. Pigment granules (melanosomes) are found within their cytoplasm. However, the frequency and size of melanosomes is highly variable between individuals and often between cells of the same iris. Clump cells are large phagocytic cells (up to 100 microns in diameter) containing lysosomes and ingested melanosomes. They are most numerous in the pupillary zone and their number increases with age.
Anterior border layer
The anterior border layer represents a modification of the stroma. Its thickness is variable, being thickest in the pupillary zone and thinned at contraction folds and absent at crypts.
The density and thickness of the border layer also varies with age and iris colour.7 Electron microscopy reveals that the anterior border layer is composed of two types of cell: melanocytes and fibroblasts (Figure 6). A discontinuous layer of fibroblasts overlies a dense aggregation of pigmented melanocytes.3
The anterior border layer is the principal determinant of iris colour: it is thin in a blue iris and thick and densely pigmented in brown irises. Local accumulations of densely pigmented melanocytes give rise to iris freckles, commonly seen in the lighter iris. Darkening of the iris is a commonly reported adverse reaction to topical prostaglandin analogues, used in the treatment of glaucoma. Morphological investigations have shown that the induced colour change results from an increased size of melanosomes within melanocytes of the anterior border layer.8
Blood supply
Arterioles pass radially from the major iridic circle in the ciliary body and form two fine vascular circles, the minor iridic circle at the collarette and the marginal arcades.
The minor iridic circle is incomplete, consisting of a series of irregular loops,9 whereas the marginal arcades form an unbroken necklace of vessels of similar lumen. Both are drained by venules that also pass radially to the ciliary body. The anterior stroma of the ciliary zone has a loose mesh of randomly orientated capillaries. A deeper, denser capillary meshwork is related to the muscles of the iris. The vessel form is adapted to the extensive motion of the iris. The vascular circles are irregular and undulating, with plenty of slack, so that when the iris undergoes contraction they are able to expand their diameters with facility. The radial vessels tend to spiral during iris contraction reducing the possibility of kinking and so maintaining vessel patency.
Vessel walls consist of unfenestrated endothelial cells, covered by pericytes and a thick fibrous adventitia. The adventitia contains fibroblasts, with long, thin processes, in a sheath of connective tissue composed of a thick, tightly-woven network of collagen fibrils. Melanocytes and tiny bundles of unmyelinated nerve fibres are occasionally present in this layer, and it may also contain macrophages and other inflammatory cells. This structure is common to all iris vessels, with a thickness usually consistent with the size of the vessel.
Whether or not the nerve fibres are true vascular terminals or merely passing to the muscles is uncertain. At the root of the iris, typical smooth muscle cells are present in the walls of the arterioles but shortly after entry into the iris they thin considerably and have the characteristic structure of pericytes.
The narrow clefts between vascular endothelial cells are closed by continuous tight junctions,10 which imparts a barrier property to these vessels (Figure 7). This barrier function contributes to the integrity of the blood-aqueous barrier that maintains a low protein concentration within the aqueous humour.
Innervation
Many small, myelinated and unmyelinated nerve fibres, parasympathetic and sympathetic respectively, enter the iris from the ciliary body plexuses of nerves.
They enter the iris radially as small discrete bundles, yet lacking a perineurium. The bundles divide as they progress through the stroma and myelin is lost well before the fibres terminate in the dilator and sphincter muscles. Some of the sympathetic fibre terminals contact melanocytes, mainly adjacent to the dilator pupillae and in the anterior border layer.5
There is tangible evidence that sympathetic terminals regulate melanin synthesis11 yet, despite considerable attention, the mechanism remains poorly understood. A link between cervical sympathetic injury and iris colour has long been known12 and in children it leads to heterochromia, whereas in adults a similar response is disputed and it appears that if the condition occurs in adults it is usually slight and slow to develop.
Trigeminal sensory fibres are present in the iris. Their number is small in man13 and their distribution is uncertain. Most of our knowledge stems from observations of substance-P-containing neurons, presumed to be sensory, but the low density in primates has also been demonstrated in degeneration studies.14 The discomfort evoked by iris stimulation, for example during laser iridotomy,15 may be attributed to stimulation of sensory endings in the iris or in the ciliary body plexus at the root of the iris.
References
1 Oyster CW The human eye. Structure and function. 1999. Sinauer Associates, Inc.
2 Freddo TF. Intercellular junctions of the iris epithelia in Mucaca mulatta. Invest Ophthalmol Vis Sci,1984; 25, 1094-1104.
3 Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. 1971. WB Saunders Company.
4 Kern R. Adrenergischen Receptoren der intraocularen Muskeln des Menschen. Ein in vitro Studie. Graefes Arch klin exptl Ophthalmol, 1970;180, 231-248.
5 Ehinger B. A comparative study of the adrenergic nerves to the anterior eye segment of some primates. Z Zellforsch, 1971; 116, 157-177.
6 van der Zypen E. The arrangement of the connective tissue in the stroma iridis of monkey and man. Exp Eye Res, 1978; 27, 349-358.
7 Okamura R, Lutjen-Drecoll E. Elektronen mikroskopische Untersuchungen uber die Altersveranderungen der menschlichen Iris. Graefes Arch klin exp Ophthalmol, 1973; 186, 249-269
8 Cracknell KP, Grierson I, Hogg P, Appleton P, Pfeiffer N. Latanoprost-induced iris darkening: a morphological study of human periperal iridectomies. Exp Eye Res, 2003; 77, 721-30.
9 Shimizu K, Ujiie K. Structure of Ocular Vessels. 1978.Tokyo, Igaku-shoin.
10 Vegge T, Ringvold A. Ultrastructure of the wall of human iris vessels. Z Zellforsch, 1969; 94, 19-31.
11 Laties AM. Ocular melanin and the adrenergic innervation of the eye. Trans Am Ophthalmol Soc, 1974; 72, 560-605.
12 Calhoun FP. Causes of heterochromia irides with special reference to paralysis of the cervical sympathetic. Am J Ophthalmol, 1919; 2, 255-269.
13 Tervo T, Tarkkanen A, Tervo K. Innervation of the human pupillary sphincter by nerve fibers immunoreactive to substance P. Ophthal Res, 1985; 17, 111-114.
14 Bergmanson JPG. The ophthalmic innervation of the uvea in monkeys. Exp Eye Res, 1977; 24, 225-240.
15 Perkins ES, Brown NAP. Iridotomy with a ruby laser. Br J Ophthalmol, 1973; 57, 487-498.
16 Lissen A, Rothova A, Valkenburg HA, Dekker-Saeys AJ, Luyendijk L, Kijlstra A, Feltkamp TE. The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to alkylosing spondylitis and histocompatability antigen HLA-B27. Invest Ophthalmoml Vis Sci,1991; 32, 2568-78.
17 Hogan MH, Kimura SJ, Tygeson, P. Signs and symptoms of uveitis I: Anterior uveitis. Am J Ophthalmol, 1959; 47, 155-70.
18 Campbell DG, Schetzer RM. Pathophysiology of pigment dispersion syndrome and pigmentary glaucoma. Curr Opin Ophthalmol, 1995; 6, 96-101.
Professor John Lawrenson works in the Department of Optometry and Visual Science at City UniversityThe iris forms the anterior part of the uveal tract, which represents the middle of the three coats of the globe.
As with the other parts of the tract, such as the ciliary body (discussed in Part 5, optician, April 30) and choroid, the iris is characterised by dense pigmentation and possesses a rich blood supply. Smooth muscle is also present to facilitate pupil dynamics.
The iris
The iris is a thin muscular diaphragm, continuous with the ciliary body and separating the anterior and posterior chambers of the eye.
The central aperture, the pupil, can vary in diameter from about 2mm to 8mm under natural conditions, governed by the actions of two smooth muscles, the sphincter and dilator pupillae (Figure 1).
The efficiency of the iris as a light stop, which is its principal function, is due to its dense pigmentation. Stromal pigment contributes to this property, but the amount is variable and the pigment epithelium on the posterior surface of the iris has primary responsibility for ensuring that light enters the eye only through the pupil. A change in pupil diameter from 2mm to 8mm represents a 16-fold increase in area. This variation in size ensures that the amount of light entering the eye is maintained within an optimal operating range by admitting more light when the ambient illumination is dim and admitting less light when the ambient illumination is bright.1
Gross appearance
The iris is approximately 12mm in diameter and 38mm in circumference. It is thickest at the collarette, an irregularly scalloped structure roughly concentric with the pupil margin (Figure 2) and thinnest at its root (0.2mm) where it attaches to the ciliary body.
The collarette overlies an incomplete vascular circle (minor iridic circle), and marks the boundary between the ciliary and pupillary zones of the iris. The ciliary zone is much the larger part of the surface of the iris, and extends from the collarette to the attachment of the iris at the ciliary body. The ciliary zone shows considerable variation in appearance due to the presence of folds, furrows, and crypts (of Fuchs) of varying size and shape. Crypts are absent or infrequent in darker races and the iris has a regular velvety texture.
In such cases, two or more peripheral circumferential folds typically disturb the regular surface. The pupillary zone has slight radial thickenings reflecting the pattern of underlying blood vessels. In a grey or blue iris, the sphincter pupillae is often visible encircling the pupil. At the pupil margin the posterior layers of the iris extend forward to form a pupillary ruff.
The posterior surface of the iris has a regular deep brown colour marked by ridges or striae converging to the iris margin, with a superimposed pattern of shallow, frequent, regularly spaced circumferential grooves. With the iris normally resting on the anterior surface of the crystalline lens, the radial ridges facilitate flow of aqueous humour from the posterior to the anterior chamber.
When the iris stroma is thin and sparsely pigmented, shorter wavelengths are selectively scattered back to the observer and the longer wavelengths penetrate to the pigmented posterior epithelial layers and are absorbed. Consequently the iris appears blue. Otherwise, melanin pigment within melanocytes is responsible for iris colour. Cells containing sparse pigment granules (melanosomes) will produce a grey colour and with increasing concentration, the colour produced is mid-brown, then dark brown. So, in the heavily pigmented iris, with a thick regular stroma, the colour is uniformly mid to dark brown and, in the less heavily pigmented iris, one or more of the colour varieties is expressed.
Often, in an otherwise poorly pigmented iris, brown freckles are present; where local clusters of anterior border layer melanocytes occur. Slight congenital difference in the colour pattern between irises of the same individual (heterochromia) is quite common. By contrast, acquired heterochromia may be drug-induced, or the result of nerve injury or neoplasia.
Histology
From the posterior surface forward, the layers of the iris are (Figure 3):
1) Posterior pigment epithelium
2) Anterior epithelium and dilator pupillae muscle
3) Substantia propria (stroma) including the sphincter pupillae muscle and the blood vessels
4) Anterior border layer.
Posterior pigment epithelium
The posterior pigment epithelium consists of melanin-rich columnar cells mounted on a thin basement membrane (Figures 4 and 5). Shallow infoldings are numerous at the basal aspect of each cell and finger-like processes extend from the lateral walls making contact with those of the neighbouring cells.
Scattered desmosomes, intermediate junctions and less numerous gap junctions link apposed walls. Adjacent cells are also joined by tight junctions at their apices.2 As well as the barrier property of tight junctions, this impressive connectivity ensures the layer's capacity to withstand the vigorous excursions of the iris. At the iris margin the posterior epithelium curls forward slightly, forming the ruff at the pupil margin.
Anterior epithelium and dilator pupillae
The anterior epithelium forms a thinner, rather less heavily pigmented layer. The anterior epithelium has two morphologically distinct portions: an apical 'epithelial' portion and a basal 'muscular' portion. The apical portion is directed towards the posterior epithelium, to which it forms frequent desmosomes and gap junction attachments.3
Lengthy, smooth muscle processes arise from the basal portion of the cell, forming the specialised dilator pupillae (Figures 4 and 5).
Muscle processes immediately turn into the plane of the iris and pass radially towards the pupil margin, producing a thin sheet of smooth muscle covering the apical portion of the epithelium. The thickness of this muscle layer varies according to the state of contraction of the iris and, when strongly contracted, several rows of muscle processes are stacked together. A basement membrane covers the muscular processes except where they are in direct apposition. In these positions, they are joined by very numerous gap junctions and infrequent desmosomes.
The dilator muscle is richly innervated by sympathetic and infrequently by parasympathetic nerve fibre terminals.4,5 Sympathetic activation induces contraction of the muscle, dilating the pupil. The dilator terminates well short of the iris margin but overlaps the outer margin of the sphincter pupillae, to which it is linked by widely spaced, slender muscle strands.
Sphincter pupillae
By light microscopy the sphincter pupillae is visible as a ribbon-like band in the posterior stroma encircling the pupillary margin (Figure 3). It is separated from the anterior epithelium, from which it is embryologically derived, by a thin sheet of connective tissue.3 The smooth muscle fibres are spindle-shaped with their axes disposed circumferentially, forming a 1mm band in the plane of the iris with a thickness of 6-10 cells, varying with the state of contraction. The cells are packed with myofilaments and numerous mitochondria with aggregations at each pole of the fusiform nucleus. Bundles of muscle fibres are partially separated from their neighbours by incomplete thin connective tissue cell partitions. Fibres within bundles, and those in apposition where bundles meet, are joined by gap junctions and desmosomes. The impressive mobility of the sphincter, required to govern pupil size, demands a substantial rearrangement of its muscle fibres.
This cannot be achieved by fibre shortening alone and fibre bundles must also overlap, producing a large increment in muscle thickness when fully contracted. Melanosomes are sometimes present in muscle fibres, indicating their pigment epithelial origin. Myelinated parasympathetic nerve fibres from the oculomotor nerve lose their myelin and terminate in the muscle. Many of the terminals lie at the perimeter of the muscle but others penetrate between the bundles with a similar relationship with muscle fibres as in the dilator. A few sympathetic nerve fibres also terminate in the sphincter muscle.4,5
Stroma (Substantia propria)
The stroma is composed of a loose network of connective tissue (Figure 4). Practically all fibrous material is collagen (type VI) set in a glycoprotein matrix and organised in a series of meshes orientated parallel to the surface, with the stronger strands directed radially.6
Cellular elements of the stroma include: fibroblasts, melanocytes, clump cells and mast cells. Fibroblasts are the most numerous of the stromal cells. These spindle-shaped cells often congregate around blood vessels, nerves and muscle fibres, where they often co-localise with melanocytes. Melanocytes possess a round or oval cell body, from which numerous long branching processes arise. Pigment granules (melanosomes) are found within their cytoplasm. However, the frequency and size of melanosomes is highly variable between individuals and often between cells of the same iris. Clump cells are large phagocytic cells (up to 100 microns in diameter) containing lysosomes and ingested melanosomes. They are most numerous in the pupillary zone and their number increases with age.
Anterior border layer
The anterior border layer represents a modification of the stroma. Its thickness is variable, being thickest in the pupillary zone and thinned at contraction folds and absent at crypts.
The density and thickness of the border layer also varies with age and iris colour.7 Electron microscopy reveals that the anterior border layer is composed of two types of cell: melanocytes and fibroblasts (Figure 6). A discontinuous layer of fibroblasts overlies a dense aggregation of pigmented melanocytes.3
The anterior border layer is the principal determinant of iris colour: it is thin in a blue iris and thick and densely pigmented in brown irises. Local accumulations of densely pigmented melanocytes give rise to iris freckles, commonly seen in the lighter iris. Darkening of the iris is a commonly reported adverse reaction to topical prostaglandin analogues, used in the treatment of glaucoma. Morphological investigations have shown that the induced colour change results from an increased size of melanosomes within melanocytes of the anterior border layer.8
Blood supply
Arterioles pass radially from the major iridic circle in the ciliary body and form two fine vascular circles, the minor iridic circle at the collarette and the marginal arcades.
The minor iridic circle is incomplete, consisting of a series of irregular loops,9 whereas the marginal arcades form an unbroken necklace of vessels of similar lumen. Both are drained by venules that also pass radially to the ciliary body. The anterior stroma of the ciliary zone has a loose mesh of randomly orientated capillaries. A deeper, denser capillary meshwork is related to the muscles of the iris. The vessel form is adapted to the extensive motion of the iris. The vascular circles are irregular and undulating, with plenty of slack, so that when the iris undergoes contraction they are able to expand their diameters with facility. The radial vessels tend to spiral during iris contraction reducing the possibility of kinking and so maintaining vessel patency.
Vessel walls consist of unfenestrated endothelial cells, covered by pericytes and a thick fibrous adventitia. The adventitia contains fibroblasts, with long, thin processes, in a sheath of connective tissue composed of a thick, tightly-woven network of collagen fibrils. Melanocytes and tiny bundles of unmyelinated nerve fibres are occasionally present in this layer, and it may also contain macrophages and other inflammatory cells. This structure is common to all iris vessels, with a thickness usually consistent with the size of the vessel.
Whether or not the nerve fibres are true vascular terminals or merely passing to the muscles is uncertain. At the root of the iris, typical smooth muscle cells are present in the walls of the arterioles but shortly after entry into the iris they thin considerably and have the characteristic structure of pericytes.
The narrow clefts between vascular endothelial cells are closed by continuous tight junctions,10 which imparts a barrier property to these vessels (Figure 7). This barrier function contributes to the integrity of the blood-aqueous barrier that maintains a low protein concentration within the aqueous humour.
Innervation
Many small, myelinated and unmyelinated nerve fibres, parasympathetic and sympathetic respectively, enter the iris from the ciliary body plexuses of nerves.
They enter the iris radially as small discrete bundles, yet lacking a perineurium. The bundles divide as they progress through the stroma and myelin is lost well before the fibres terminate in the dilator and sphincter muscles. Some of the sympathetic fibre terminals contact melanocytes, mainly adjacent to the dilator pupillae and in the anterior border layer.5
There is tangible evidence that sympathetic terminals regulate melanin synthesis11 yet, despite considerable attention, the mechanism remains poorly understood. A link between cervical sympathetic injury and iris colour has long been known12 and in children it leads to heterochromia, whereas in adults a similar response is disputed and it appears that if the condition occurs in adults it is usually slight and slow to develop.
Trigeminal sensory fibres are present in the iris. Their number is small in man13 and their distribution is uncertain. Most of our knowledge stems from observations of substance-P-containing neurons, presumed to be sensory, but the low density in primates has also been demonstrated in degeneration studies.14 The discomfort evoked by iris stimulation, for example during laser iridotomy,15 may be attributed to stimulation of sensory endings in the iris or in the ciliary body plexus at the root of the iris.
References
1 Oyster CW The human eye. Structure and function. 1999. Sinauer Associates, Inc.
2 Freddo TF. Intercellular junctions of the iris epithelia in Mucaca mulatta. Invest Ophthalmol Vis Sci,1984; 25, 1094-1104.
3 Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. 1971. WB Saunders Company.
4 Kern R. Adrenergischen Receptoren der intraocularen Muskeln des Menschen. Ein in vitro Studie. Graefes Arch klin exptl Ophthalmol, 1970;180, 231-248.
5 Ehinger B. A comparative study of the adrenergic nerves to the anterior eye segment of some primates. Z Zellforsch, 1971; 116, 157-177.
6 van der Zypen E. The arrangement of the connective tissue in the stroma iridis of monkey and man. Exp Eye Res, 1978; 27, 349-358.
7 Okamura R, Lutjen-Drecoll E. Elektronen mikroskopische Untersuchungen uber die Altersveranderungen der menschlichen Iris. Graefes Arch klin exp Ophthalmol, 1973; 186, 249-269
8 Cracknell KP, Grierson I, Hogg P, Appleton P, Pfeiffer N. Latanoprost-induced iris darkening: a morphological study of human periperal iridectomies. Exp Eye Res, 2003; 77, 721-30.
9 Shimizu K, Ujiie K. Structure of Ocular Vessels. 1978.Tokyo, Igaku-shoin.
10 Vegge T, Ringvold A. Ultrastructure of the wall of human iris vessels. Z Zellforsch, 1969; 94, 19-31.
11 Laties AM. Ocular melanin and the adrenergic innervation of the eye. Trans Am Ophthalmol Soc, 1974; 72, 560-605.
12 Calhoun FP. Causes of heterochromia irides with special reference to paralysis of the cervical sympathetic. Am J Ophthalmol, 1919; 2, 255-269.
13 Tervo T, Tarkkanen A, Tervo K. Innervation of the human pupillary sphincter by nerve fibers immunoreactive to substance P. Ophthal Res, 1985; 17, 111-114.
14 Bergmanson JPG. The ophthalmic innervation of the uvea in monkeys. Exp Eye Res, 1977; 24, 225-240.
15 Perkins ES, Brown NAP. Iridotomy with a ruby laser. Br J Ophthalmol, 1973; 57, 487-498.
16 Lissen A, Rothova A, Valkenburg HA, Dekker-Saeys AJ, Luyendijk L, Kijlstra A, Feltkamp TE. The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to alkylosing spondylitis and histocompatability antigen HLA-B27. Invest Ophthalmoml Vis Sci,1991; 32, 2568-78.
17 Hogan MH, Kimura SJ, Tygeson, P. Signs and symptoms of uveitis I: Anterior uveitis. Am J Ophthalmol, 1959; 47, 155-70.
18 Campbell DG, Schetzer RM. Pathophysiology of pigment dispersion syndrome and pigmentary glaucoma. Curr Opin Ophthalmol, 1995; 6, 96-101.
Professor John Lawrenson works in the Department of Optometry and Visual Science at City UniversityThe iris forms the anterior part of the uveal tract, which represents the middle of the three coats of the globe.
As with the other parts of the tract, such as the ciliary body (discussed in Part 5, optician, April 30) and choroid, the iris is characterised by dense pigmentation and possesses a rich blood supply. Smooth muscle is also present to facilitate pupil dynamics.
The iris
The iris is a thin muscular diaphragm, continuous with the ciliary body and separating the anterior and posterior chambers of the eye.
The central aperture, the pupil, can vary in diameter from about 2mm to 8mm under natural conditions, governed by the actions of two smooth muscles, the sphincter and dilator pupillae (Figure 1).
The efficiency of the iris as a light stop, which is its principal function, is due to its dense pigmentation. Stromal pigment contributes to this property, but the amount is variable and the pigment epithelium on the posterior surface of the iris has primary responsibility for ensuring that light enters the eye only through the pupil. A change in pupil diameter from 2mm to 8mm represents a 16-fold increase in area. This variation in size ensures that the amount of light entering the eye is maintained within an optimal operating range by admitting more light when the ambient illumination is dim and admitting less light when the ambient illumination is bright.1
Gross appearance
The iris is approximately 12mm in diameter and 38mm in circumference. It is thickest at the collarette, an irregularly scalloped structure roughly concentric with the pupil margin (Figure 2) and thinnest at its root (0.2mm) where it attaches to the ciliary body.
The collarette overlies an incomplete vascular circle (minor iridic circle), and marks the boundary between the ciliary and pupillary zones of the iris. The ciliary zone is much the larger part of the surface of the iris, and extends from the collarette to the attachment of the iris at the ciliary body. The ciliary zone shows considerable variation in appearance due to the presence of folds, furrows, and crypts (of Fuchs) of varying size and shape. Crypts are absent or infrequent in darker races and the iris has a regular velvety texture.
In such cases, two or more peripheral circumferential folds typically disturb the regular surface. The pupillary zone has slight radial thickenings reflecting the pattern of underlying blood vessels. In a grey or blue iris, the sphincter pupillae is often visible encircling the pupil. At the pupil margin the posterior layers of the iris extend forward to form a pupillary ruff.
The posterior surface of the iris has a regular deep brown colour marked by ridges or striae converging to the iris margin, with a superimposed pattern of shallow, frequent, regularly spaced circumferential grooves. With the iris normally resting on the anterior surface of the crystalline lens, the radial ridges facilitate flow of aqueous humour from the posterior to the anterior chamber.
When the iris stroma is thin and sparsely pigmented, shorter wavelengths are selectively scattered back to the observer and the longer wavelengths penetrate to the pigmented posterior epithelial layers and are absorbed. Consequently the iris appears blue. Otherwise, melanin pigment within melanocytes is responsible for iris colour. Cells containing sparse pigment granules (melanosomes) will produce a grey colour and with increasing concentration, the colour produced is mid-brown, then dark brown. So, in the heavily pigmented iris, with a thick regular stroma, the colour is uniformly mid to dark brown and, in the less heavily pigmented iris, one or more of the colour varieties is expressed.
Often, in an otherwise poorly pigmented iris, brown freckles are present; where local clusters of anterior border layer melanocytes occur. Slight congenital difference in the colour pattern between irises of the same individual (heterochromia) is quite common. By contrast, acquired heterochromia may be drug-induced, or the result of nerve injury or neoplasia.
Histology
From the posterior surface forward, the layers of the iris are (Figure 3):
1) Posterior pigment epithelium
2) Anterior epithelium and dilator pupillae muscle
3) Substantia propria (stroma) including the sphincter pupillae muscle and the blood vessels
4) Anterior border layer.
Posterior pigment epithelium
The posterior pigment epithelium consists of melanin-rich columnar cells mounted on a thin basement membrane (Figures 4 and 5). Shallow infoldings are numerous at the basal aspect of each cell and finger-like processes extend from the lateral walls making contact with those of the neighbouring cells.
Scattered desmosomes, intermediate junctions and less numerous gap junctions link apposed walls. Adjacent cells are also joined by tight junctions at their apices.2 As well as the barrier property of tight junctions, this impressive connectivity ensures the layer's capacity to withstand the vigorous excursions of the iris. At the iris margin the posterior epithelium curls forward slightly, forming the ruff at the pupil margin.
Anterior epithelium and dilator pupillae
The anterior epithelium forms a thinner, rather less heavily pigmented layer. The anterior epithelium has two morphologically distinct portions: an apical 'epithelial' portion and a basal 'muscular' portion. The apical portion is directed towards the posterior epithelium, to which it forms frequent desmosomes and gap junction attachments.3
Lengthy, smooth muscle processes arise from the basal portion of the cell, forming the specialised dilator pupillae (Figures 4 and 5).
Muscle processes immediately turn into the plane of the iris and pass radially towards the pupil margin, producing a thin sheet of smooth muscle covering the apical portion of the epithelium. The thickness of this muscle layer varies according to the state of contraction of the iris and, when strongly contracted, several rows of muscle processes are stacked together. A basement membrane covers the muscular processes except where they are in direct apposition. In these positions, they are joined by very numerous gap junctions and infrequent desmosomes.
The dilator muscle is richly innervated by sympathetic and infrequently by parasympathetic nerve fibre terminals.4,5 Sympathetic activation induces contraction of the muscle, dilating the pupil. The dilator terminates well short of the iris margin but overlaps the outer margin of the sphincter pupillae, to which it is linked by widely spaced, slender muscle strands.
Sphincter pupillae
By light microscopy the sphincter pupillae is visible as a ribbon-like band in the posterior stroma encircling the pupillary margin (Figure 3). It is separated from the anterior epithelium, from which it is embryologically derived, by a thin sheet of connective tissue.3 The smooth muscle fibres are spindle-shaped with their axes disposed circumferentially, forming a 1mm band in the plane of the iris with a thickness of 6-10 cells, varying with the state of contraction. The cells are packed with myofilaments and numerous mitochondria with aggregations at each pole of the fusiform nucleus. Bundles of muscle fibres are partially separated from their neighbours by incomplete thin connective tissue cell partitions. Fibres within bundles, and those in apposition where bundles meet, are joined by gap junctions and desmosomes. The impressive mobility of the sphincter, required to govern pupil size, demands a substantial rearrangement of its muscle fibres.
This cannot be achieved by fibre shortening alone and fibre bundles must also overlap, producing a large increment in muscle thickness when fully contracted. Melanosomes are sometimes present in muscle fibres, indicating their pigment epithelial origin. Myelinated parasympathetic nerve fibres from the oculomotor nerve lose their myelin and terminate in the muscle. Many of the terminals lie at the perimeter of the muscle but others penetrate between the bundles with a similar relationship with muscle fibres as in the dilator. A few sympathetic nerve fibres also terminate in the sphincter muscle.4,5
Stroma (Substantia propria)
The stroma is composed of a loose network of connective tissue (Figure 4). Practically all fibrous material is collagen (type VI) set in a glycoprotein matrix and organised in a series of meshes orientated parallel to the surface, with the stronger strands directed radially.6
Cellular elements of the stroma include: fibroblasts, melanocytes, clump cells and mast cells. Fibroblasts are the most numerous of the stromal cells. These spindle-shaped cells often congregate around blood vessels, nerves and muscle fibres, where they often co-localise with melanocytes. Melanocytes possess a round or oval cell body, from which numerous long branching processes arise. Pigment granules (melanosomes) are found within their cytoplasm. However, the frequency and size of melanosomes is highly variable between individuals and often between cells of the same iris. Clump cells are large phagocytic cells (up to 100 microns in diameter) containing lysosomes and ingested melanosomes. They are most numerous in the pupillary zone and their number increases with age.
Anterior border layer
The anterior border layer represents a modification of the stroma. Its thickness is variable, being thickest in the pupillary zone and thinned at contraction folds and absent at crypts.
The density and thickness of the border layer also varies with age and iris colour.7 Electron microscopy reveals that the anterior border layer is composed of two types of cell: melanocytes and fibroblasts (Figure 6). A discontinuous layer of fibroblasts overlies a dense aggregation of pigmented melanocytes.3
The anterior border layer is the principal determinant of iris colour: it is thin in a blue iris and thick and densely pigmented in brown irises. Local accumulations of densely pigmented melanocytes give rise to iris freckles, commonly seen in the lighter iris. Darkening of the iris is a commonly reported adverse reaction to topical prostaglandin analogues, used in the treatment of glaucoma. Morphological investigations have shown that the induced colour change results from an increased size of melanosomes within melanocytes of the anterior border layer.8
Blood supply
Arterioles pass radially from the major iridic circle in the ciliary body and form two fine vascular circles, the minor iridic circle at the collarette and the marginal arcades.
The minor iridic circle is incomplete, consisting of a series of irregular loops,9 whereas the marginal arcades form an unbroken necklace of vessels of similar lumen. Both are drained by venules that also pass radially to the ciliary body. The anterior stroma of the ciliary zone has a loose mesh of randomly orientated capillaries. A deeper, denser capillary meshwork is related to the muscles of the iris. The vessel form is adapted to the extensive motion of the iris. The vascular circles are irregular and undulating, with plenty of slack, so that when the iris undergoes contraction they are able to expand their diameters with facility. The radial vessels tend to spiral during iris contraction reducing the possibility of kinking and so maintaining vessel patency.
Vessel walls consist of unfenestrated endothelial cells, covered by pericytes and a thick fibrous adventitia. The adventitia contains fibroblasts, with long, thin processes, in a sheath of connective tissue composed of a thick, tightly-woven network of collagen fibrils. Melanocytes and tiny bundles of unmyelinated nerve fibres are occasionally present in this layer, and it may also contain macrophages and other inflammatory cells. This structure is common to all iris vessels, with a thickness usually consistent with the size of the vessel.
Whether or not the nerve fibres are true vascular terminals or merely passing to the muscles is uncertain. At the root of the iris, typical smooth muscle cells are present in the walls of the arterioles but shortly after entry into the iris they thin considerably and have the characteristic structure of pericytes.
The narrow clefts between vascular endothelial cells are closed by continuous tight junctions,10 which imparts a barrier property to these vessels (Figure 7). This barrier function contributes to the integrity of the blood-aqueous barrier that maintains a low protein concentration within the aqueous humour.
Innervation
Many small, myelinated and unmyelinated nerve fibres, parasympathetic and sympathetic respectively, enter the iris from the ciliary body plexuses of nerves.
They enter the iris radially as small discrete bundles, yet lacking a perineurium. The bundles divide as they progress through the stroma and myelin is lost well before the fibres terminate in the dilator and sphincter muscles. Some of the sympathetic fibre terminals contact melanocytes, mainly adjacent to the dilator pupillae and in the anterior border layer.5
There is tangible evidence that sympathetic terminals regulate melanin synthesis11 yet, despite considerable attention, the mechanism remains poorly understood. A link between cervical sympathetic injury and iris colour has long been known12 and in children it leads to heterochromia, whereas in adults a similar response is disputed and it appears that if the condition occurs in adults it is usually slight and slow to develop.
Trigeminal sensory fibres are present in the iris. Their number is small in man13 and their distribution is uncertain. Most of our knowledge stems from observations of substance-P-containing neurons, presumed to be sensory, but the low
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