Corneal Endothelial Cell Abnormalities in an Early Stage of the Iridocorneal Endothelial Syndrome

624 BritishJournalofOphthalmology 1994; 78: 624-631

ORIGINAL ARTICLES - Laboratory science Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from

Corneal endothelial cell abnormalities in an early stage of the iridocorneal endothelial syndrome

W R Lee, G E Marshall, C M Kirkness

Abstract appearance with a central highlight and a light A corneal disc, obtained from a 52-year-old peripheral surround.2-5 The presence of ICE cells woman suffering from an early stage of the can herald (a) corneal oedema with a normal IOP iridocorneal endothelial syndrome (ICE), was and band-shaped keratopathy, (b) glaucoma investigated by various morphological tech- caused by ICE cell migration across the niques to analyse the structural variations trabecular meshwork (Chandler's syndrome), in the endothelial cells and to identify the (c) glaucoma associated with iris atrophy (essen- collagen types within the abnormal layer of tial iris atrophy), or (d) iris melanocytic neoplasia Descemet's membrane. Scanning electron (iris naevus syndrome).'1 It is clear, however, microscopy of the posterior corneal surface that a spectrum of disease exists and many revealed a mosaic of (a) flat hexagonal cells patients exhibit features of more than one of the resembling irregular but normal endothelial classically described syndromes. cells, and (b) rounded hexagonal (ICE) cells In pathological material, endothelial mor- with numerous surface microvilli. Degenera- phology has been inconsistent. By light micro- tive changes were present in each cell type, but scopy, the endothelial cell population is depleted were more common in the flat hexagonal cells in some cases, particularly in Chandler's syn- which contained intracytoplasmic spaces. By drome,"8 and occasionally multilayered,9 transmission electron microscopy the flat hex- although in the majority of specimens the cells agonal cells exhibited many of the features of have formed a degenerate monolayer.90' By scan- normal endothelial cells in terms of organelles ning electron microscopy, the presence of and intercellular attachments, but lateral abundant surface microvilli over hemispherical invaginations were absent. The ICE cells cells and cytoplasmic blebbing have been the

differed in that the apical surface was covered most noteworthy feature of ICE cells.'0 Flat http://bjo.bmj.com/ by microvilli and the cytoplasm contained hexagonal cells which varied considerably in size tonofilaments, which were also observed by and shape have also been recorded as a mosaic light microscopic immunocytochemical stain- or subpopulation on the posterior corneal ing. Most commonly, intercellular attach- surface.591I ments were rudimentary in both types of cell By transmission electron microscopy ICE cells and intercellular spaces were dilated, but have been shown to have endothelial cell

desmosomes were sometimes prominent in the characteristics."' 12 By contrast, ICE cells have on September 28, 2021 by guest. Protected copyright. ICE cells where interdigitations were pro- been shown to have epithelial characteristics nounced. In some sectors, the basal surface of with desmosomes6 1213 and intracytoplasmic the ICE cells was indented by deposition of tonofilaments.68 1012 13 clumps of fibrillar collagenous material. An Descemet's membrane which normally con- immunocytochemical study of the abnormal tains two collagen types (IV and VIII)' 16 iS posterior deposits localised type IV collagen to thickened in ICE by the addition of a broad the amorphous matrix and collagen types III posterior collagenous layer (PCL)6IO'2 '7 occa- and V, but not type I, to the collagen fibril sionally containing wide banded collagen.9'7 bundles. Mononuclear inflammatory cells Small foci of fibrillar deposits behind the pos- were identified between the ICE cells in the terior non-banded zone were reported in one monolayer. The evidence suggests that some example of the early stage of the disease.'0 An University ofGlasgow of the flat hexagonal cells were undergoing a attempt to identify the collagen types in the Department of degenerative change while others were trans- PCL has not to our knowledge been attempted. Ophthalmology forming into ICE cells. In the present morphological study we describe W R Lee (Brj' Ophthalmol 1994; 78: 624631) the features of the endothelium in an early G E Marshall C M Kirkness uncomplicated case of the ICE syndrome in which, with the application of immunogold Department of The iridocorneal endothelial (ICE) syndrome is a immunocytochemistry, we have identified some Pathology rare W R Lee non-familial unilateral disorder which pro- of the constituents of the abnormal posterior G E Marshall gresses to glaucoma and is characterised clinic- collagenous layer which is secreted by the ICE Correspondence to: ally by a fine beaten silver appearance of all or cells. Professor W R Lee, Pathology part of the posterior corneal surface as seen by Department, Western Infirmary, Glasgow GIl 6NT. slit-lamp specular microscopy.'2 By endothelial Accepted for publication specular photomicroscopy, abnormal endo- Clinical history 8 February 1994 thelial cells (ICE cells) have a characteristic A female patient (born 10 May 1941) attended Cornealendothelial cell abnormalities in an early stage ofthe iridocorneal endothelial syndrome 625

the Tennent Institute in January 1993 with a Paraffin sections were stained with haema- unilateral decrease in visual acuity which was toxylin and eosin, periodic acid Schiff, and associated with some diurnal fluctuation in Masson and were also used for an immuno- Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from vision, the vision being worst in the morning and histochemical study of cytokeratins in the clearing slightly by mid-day. Such symptoms epithelium and the endothelium. The following had persisted for 5 years. There was no family antibodies were applied - CAM 5-2, AE 1/3, history ofcorneal disease. The referring ophthal- NCL, and MNF. The tissue for transmission mologist considered that the anterior chamber electron microscopy was processed through to was shallow and that a few peripheral anterior Araldite and semithin sections were stained with *synechiae were present. On examination toluidine blue. Ultrathin sections were examined the vision in the affected eye was reduced to in a Jeol 1200 EXII transmission electron micro- 6/24 with correction. There was stromal and scope. The quadrant used for scanning electron epithelial corneal oedema and a distorted microscopy was subject to critical point drying eccentric pupil with ectropion uveae. Fine endo- before gold coating and examination in a Jeol thelial detail was obscured by the oedema. No JSM 64000 scanning electron microscope. The other features were distinguishable and in block allocated for immunocytochemistry was particular the other eye was entirely normal. processed for London resin (LR) white embed- Intraocular pressure in both eyes was within ding. Details of the techniques for embedding, normal limits. Endothelial specular photomicro- antibody labelling, and immunocytochemistry scopy (ESP) was performed with considerable have been provided elsewhere. 145S difficulty because ofthe corneal oedema. In some areas, cells with central highlights were visible. Clinically this was felt to be ICE syndrome Results because of the unilaterality, the ESP appearance and the lack ofany clinical features suggestive of LIGHT MICROSCOPY posterior polymorphous dystrophy - namely, The epithelium was oedematous and the base- vesicles, snail track, and thickened Descemet's ment membrane was multilayered and infolded membrane. The small ectropion uveae was also in parts: there was no evidence of a band felt to be consistent with the ICE syndrome. keratopathy. Bowman's layer was intact and A corneal graft was performed on 12 January there were plentiful stromal keratocytes, but in 1993 and at follow up 9 months later the graft has one halfofthe cornea the lamellae appeared to be remained clear and the intraocular pressure has more widely dispersed owing to oedema. remained normal. Descemet's membrane measured 6 jim but there was evidence ofmultilayering in the PAS stained sections (Fig 1). The normal cuboidal endo- Materials and methods thelium was replaced either by vacuolated cells The keratoplasty disc measured 8 mm in or rounded cells and some cells were remarkably

diameter and the stroma was cloudy. The speci- attenuated (Figs la, lb). Mononuclear inflam- http://bjo.bmj.com/ men was divided into four, and three parts were matory cells were present within the monolayer fixed in glutaraldehyde (2%) for paraffin histo- (Fig lb). Consistent results were obtained with logy, scanning electron microscopy, and conven- the immunohistochemical markers for cyto- tional transmission electron miscoscopy. The keratins. The rounded ICE cells stained remaining part was fixed in a paraformaldehyde positively while the flattened and vacuolated (4%)/glutaraldehyde (0-5%) mixture for 2 hours cells were weakly staining (Fig ld). The

at room temperature for immunogold immuno- epithelium stained positively for each of the on September 28, 2021 by guest. Protected copyright. cytochemistry. 14 15 antibodies used.

- .R .Lk...... *. ....p...... 011.OffiftI III 11111.... i.'I. -.... T.T. Figure I Light micrographs ofthe posterior corneal surface. (a) Vacuoles lpq'- :% . (arrowheads) were a ,#& *Ai prominentfeature in some I A areas ofthe endothelium. (b) b In other sectors the cells were a rounded and inflammatory cells (arrowheads) could be identified in the monolayer. (c) In theperiodic acidSchiff stainedparaffin section, Descemet's membrane (arrowheads) appears bilayered and the endothelial cells are vacuolated or attenuated. ((a) and (b) Araldite toluidene blue, x630; (c) paraffin x 750.) (d) Some ofthe cells (corresponding to rounded wr..... I'mmi'l cells) on the posterior surface 7T..- "11-1. --w I....."I stain positively with cytokeratin markers while other cells (corresponding to theflat vacuolated cells) are negative (CAM 5 2). d 626 Lee, Marshall, Kirkness

Figure 2 Features ofthe posterior corneal surface as seen by scanning electron microscopy. (a) Low power Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from view oftheflat hexagonal cells: note the degenerating cells (arrowheads). (b) Higherpower to contrast the surface ofhexagonal cells with that ofthe ICE cells which are covered by microvilli: note cilia on the surface ofthe hexagonal cells (arrowheads). (c) The ICE cells sometimes showed widening ofthe intercellular spaces (arrow): note ruptured cyst in the hexagonal cells (arrowhead). (d) The ICE cells haveprominent nuclear bulges and cilia (arrowheads). ((a) x800; (b) xSOOO; (c) x 1600; (d) x1400.) http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.

SCANNING ELECTRON MICROSCOPY ruptured cysts were observed within hemis- The appearance of the cells on the posterior pherical cell populations than among hexagonal comeal surface varied considerably. Small areas cells. Binucleate cells were not seen. of flat cells resembled the normal hexagonal endothelium, but there was marked variation in shape and diameter (from 10 to 20 iim) of these TRANSMISSION ELECTRON MICROSCOPY cells (Fig 2). Cilia were present and the edges of the cells were lined by microvilli (Fig 2b). Hexagonal cells Ruptured cystic blebs exposed the cytoplasmic These were identified as endothelial cells by the contents and extruded cytoplasmic debris lay on smooth posterior surface, typical mitochondria the surface of the adjacent hexagonal cells. with tubular cristae, cilia, and a paucity of The majority of the cells were more regular in cytoplasmic filaments. Some cells contained shape and size being hemispherical and covered isolated melanosomes (Fig 3) and areas of intra- by numerous microvilli: these cells are conven- cytoplasmic rarefaction and, in some groups of tionally referred to as ICE cells. The microvilli cells, what appeared to be large intracytoplasmic were fewer in the central part of the cell, where cysts were found. Intercellular lateral infoldings there was a bulge and here a central cilium was were not pronounced, but the junctions were easily identified. In other areas intercellular those of the normal endothelium: occasionally spaces were pronounced. Considerably fewer the intercellular space was widened (Fig 3). Corneal endothelial cell abnormalities in an early stage ofthe iridocorneal endothelial syndrome 627

Figure 3 (a) The hexagonal cells with aflat posterior surface contain numerous mitochondria and Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from melanosomes:focal dilatations are present in the =t &2C' N ' C t g intercellular space (arrows) -P 4 e and within the cell $ I~~~~~~~0 ' W .44 (arrowhead). (b) A cilium ..:... 3 within a cell (arrowhead) .1.. which contains intracytoplasmic vacuoles. Note the close apposition ..... between the cells and Descemet's membrane, and numerous mitochondria. ((a) and (b) x 7000.)

Hemispherical (ICE) cells IMMUNOGOLD IMMUNOCYTOCHEMISTRY These were characterised by numerous micro- Collagen types I, III, and V were localised to villi on the posterior surface, abundant intra- striated collagen fibrils in Bowman's layer and in cytoplasmic filaments (80-100 nm diameter) the corneal stroma (Fig 7). Labelling for type IV (Fig 4) and mitochondria with lamellar cristae collagen was present in the posterior non-banded (Fig 5). Intercellular indentations were some- zone of Descemet's membrane (Fig 8), but was times prominent and desmosomal atachments absent from the basement membrane of the were an occasional finding. Some of the cells corneal epithelium. No labelling for type II contained an isolated melanosome. Inflamma- collagen was seen in any of the regions studied. tory cells (mainly lymphocytes and a few macro- The localisation of collagen types I-V in the phages) were present within the monolayer. present specimen, excepting Descemet's mem- Descemet's membrane was thickened beneath brane (see below), was therefore identical to that the ICE cells by irregular deposition ofclumps of seen in immunogold studies of aged human striated fibrils embedded in an amorphous cornea. 1-16 matrix: these nodules also projected into the cells The accumulations of striated collagen fibrils (Fig 6). Wide banded collagen was absent. which were observed between the ICE cells and Descemet's membrane were arranged either in whorls which invaginated the adluminal surface

of the cells (Figs 8, 9) or in long thin bundles http://bjo.bmj.com/ lying parallel to the endothelial surface (Fig 6). Both arrangements of fibrils exhibited intense labelling for collagen types III and V (Fig 9) and type IV was present in the enveloping amorphous matrix (Fig 8). Labelling for types I, II, and IV collagen was consistently absent from

such fibril accumulations. on September 28, 2021 by guest. Protected copyright. Immunogold particles were rarely observed in the rabbit antigoat immunogold control sections (omission of primary antibody) and were sparse in the normal goat serum control sections (that is, substitution of the primary antibody with non-immune serum from the same species in which the primary antibody was a raised).

Discussion Many ofthe cases reported as the ICE syndrome have been taken from patients suffering from abnormalities additional to those in the cornea. The value of the present case lies in the fact that it represents the disease at an early and Figure 4 Degenerative uncomplicated changes in theICE cells were stage. seen as enlarged spaces In the present case, light microscopy was of within the cytoplasm and value in confirmation of the clinical diagnosis of between the cells (arrowhead, shown in (a)) the ICE syndrome, because the flat vacuolated and numerous pinocytotic endothelial cells were easily distinguished from vesicles adjacent to the the humped ICE cells and immunocytochemistry microvilli (arrow, shown in identified cytokeratins (b)). Note the prominent in the latter cells. The intracytoplasmicfilaments in focal positivity and minor variations we observed the cells. (Araldite (a) were also noted by Kramer et al,'° while more x 2000; (b) x 10 000.) extensive staining was reported by Hirst et al'2: 628 Lee, Marshall, Kirkness

FigureS ...... The .... ultrastructural appearances Y ofthe ICE cells within the t,k. 'JI

endothelium. (a) A low Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from ...... power view to show cells ...... a ...... with prominent microvilli...... (b) A mononuclear 11-9 .. inflammatory cell is present . Wz:,. M .1 within the monolayer SEEM (arrow). (c) In some areas ...... A desmosomal attachments -.d (arrowheads) are present on the interdigitating cell membranes. (d) Dense contractilefilaments are ...... present within the cytoplasm ofsome ICE cells. ((a) .. ... x2000; (b) x 10000; (c) ...... x25 000; (d) x100 000.)

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these differences may reflect the change from flat variations in cell morphology. The differences in hexagonal cells to ICE cells as the disease pro- appearance of the flat hexagonal cells and the gresses and at the end stage multilayering has ICE cells in the case were present very similar to on September 28, 2021 by guest. Protected copyright. been observed within the population.9 0 112 13 The those previously reported in various disorders in presence of vacuolation in a distinct the monolayer ICE group,58 10 12 with some cells exhibiting over a relatively thin Descemet's membrane is transitional features between the flat and micro- dissimilar to many of the cases described in the villous surfaces. Not all cases ICE classified as ICE in literature, particularly in the reports of the literature have demonstrated a continuous Chandler's syndrome in which Descemet's monolayer and illustrations of isolated cells with membrane was thickened and the cells were extended processes over an exposed Descemet's attenuated and/or duplicated.689 11-13 Another membrane have appeared.68 3 This extreme discrepancy is that cystic blebbing (Fig 2) was stage of endothelial degeneration and atrophy more common in the hexagonal cells compared appears to be associated with extension of with the ICE cells the in the present case, rather than endothelium over the chamber angle onto the iris in the ICE cells as has been reported by others.7 9 surface and therefore to massive of A thickness of 6 of depopulation [tm Descemet's membrane the corneal endothelium as in Chandler's syn- was a surprising feature in the present case since drome. Depopulation is preceded by cell migra- in all of the other published reports, Descemet's tion and this is membrane has been change probably expressed as markedly thickened.6>'3'7 filopodial extension as seen by scanning electron light was By microscopy it also possible to microscopy,"8'9 but this was not identify mononuclear inflammatory cells abnormality within observed in other cases' 12 or in the present case. the endothelium, but this feature, as these This substantiates the authors7-9 have impression that flat stated, can only be regarded as hexagonal cells are present in the endothelium at supplemental to the diagnosis and is regarded as the earliest stage of the disease. non-specific in other corneal disorders. One of the striking features of the hemi- Scanning electron microscopy ofthe abnormal spherical ICE cells is that cannot be classi- endothelium in the ICE they syndrome provides a fied as typical endothelial or epithelial cells on great deal of additional information concerning the basis of their ultrastructural features. While Corneal endothelial cellabnormalities in an early stage ofthe iridocorneal endothelial syndrome 629

Figure 6 (a) Between the posterior collagenous layer

and the ICE cells there is a Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from ...... layer ofabnormal ,,5.'4~F extracellular matrix (arrowheads) shown at higher magnification in (b) where there are bundles of la. collagenfibrils within an amorphous matrix. ((a) x5000; (b) x20 000.) X .... _;,...... i J ...... >A .... -CF.. ... , _...... * S~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~......

...... a ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..

**~~~~~~~~~~~~~~~~~~~~~~~WX , ..~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.

Figure 7 (a) The interfibrillar matrix (IFM) ofthe posterior stroma exhibits labellingfor type I collagen. (b) Labellingfor type I collagen is completely negative in the posterior non- banded zone (PNBZ) and in a linear accumulation of collagenfibrils (CF) at the endothelialface ofDescemet's membrane. Note absence oflabelfrom endothelial cytoplasm and nucleus. ((a) and (b) London resin white x30 000.) http://bjo.bmj.com/

These differences are regarded by morphologists as of considerable importance in ascertaining the histogenetic origin of a cell population, but in the microvilli have been described in several case of the corneal endothelium, derived from papers91012 and cytoplasmic blebbing in the neural crest cells with a specific potential

report by Alvarado et al19 only four authors have for metaplasia, the commonly accepted rules for on September 28, 2021 by guest. Protected copyright. emphasised the presence of intracytoplasmic an ectodermal or mesodermal origin do not tonofilaments6 8 10 12 and desmosomal attach- apply. The mixture of cytoplasmic membrane ments, 13 which characterise the cells as characteristics observed in the cells on the epithelial. Prominent tonofilaments and posterior cornea suggests that there is a transfor- desmosomal attachments between multilayered mation from hexagonal cells to ICE cells and that cells favour a diagnosis of posterior poly- the viability of the endothelial cells is lower than morphous dystrophy (PPD), but for this that of the ICE cells. unequivocal diagnosis an identifiable inheritance The presence of inter- and intracytoplasmic pattern and bilaterality are required.4 It is poss- blebs in the flat hexagonal cells is strong evidence ible that there is an overlap between PPD and the in favour of a functional failure to control water ICE syndrome and there has been considerable movement. It is tempting to suggest that the interest and speculation in the metaplastic poten- transformation to ICE cells with complex inter- tial of the corneal endothelium, which may be digitations is an attempt to restore the functional based on its origin from the neural crest. 18 integrity of the posterior monolayer. This would The appearances of the dual cell population be a stress response and it is reasonable to assume in the present case resembled in part the that synthesis of a new posterior collagenous endothelial-type cells described by Alvarado layer is part of that response. The presence of et al9 and the epithelial-type cells described by microvilli would increase the surface area of the Kramer et al.'0 The flat hexagonal cells did not cell membrane, so that this may be an aberrant have the typical features of endothelial cells in attempt to control water movement. The terms of intercellular boundaries, but contained presence ofleaking and non-leaking areas ofcells the characteristic mitochondria and cilia. The may be relevant to the unpredictable nature of epithelial-type cells exhibited intercellular corneal oedema in the ICE syndrome. A decrease invaginations, but were united by desmosomal in water movement across the cornea in the ICE attachments and lined internally by microvilli. syndrome has been demonstrated by Bourne and 630 Lee, Marshall, Kirkness

wo f.w...: - ing number of ICE cells and that ICE cells can regress in an individual patient with a perme- ability returning to normal. The corneas in such Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from

...... patients would not be available for morphological study, but the in vivo evidence suggests ...... B. r~~~~~~~~~~.....I-.... that in some ICE corneas there may be a trans- formational return to a cell monolayer which -^= possesses the capacity to restrict water movement. If the concept is accepted that there is a capacity for recovery in some cases of ICE, the inflammatory basis for an unilateral disease as ...proposed by Alvarado et al9 has some basis. In the present specimen lymphocytes were found without difficulty in the endothelium among both the ICE cells and the relatively normal hexagonal cells. Inflammatory cells within the endothelium are a striking abnormality and have been recorded in two publica- tions78 in addition to that of Alvarado et al.9 e Rodrigues et al7 suggested that an endotheliitis 7 | may be linked with a low grade iritis or that these cells are 'incidental' cells. ''8~- wandering Certainly the presence of melanosomes within the hexagonal cells and the ICE cells suggests that there had been some breakdown of the pig- mented cells ofthe iris. The mononuclear inflammatory cells, lymphocytes, and macrophages may be respons- ible for the degenerative changes, vacuolation, and cell death described in the endothelial cell population in other reports8 9 and in the present case. In the present case it was apparent that the striated collagen fibres deposited presumably by the ICE cells contained types III and V and the amorphous matrix contained type IV. Type I collagen is not normally found in Descemet's V was located in the ik membrane,'4 type collagen .w. L..s:. il j* interfacial matrix between the stromal collagen http://bjo.bmj.com/ I 4 0 *^* -and the anterior banded zone,'4"5 and type VIII collagen is located to the hexagonal lattice Figure 8 Type IV collagen material of the anterior banded zone.'6 It can labelling ispresent within the therefore be concluded that the cells in the ICE posterior non-banded zone oresis were synthetically active but that the (PNBZ) and over the Brubaker"9 using the iontoph technique syndrome amorphous material around with fluorescein. Bourne and Brubaker"' have activity was aberrant in some aspects.

a whorl ofcollagenfilbrils shown more recently that the peermeability ofthe Cell culture experiments underline the latent on September 28, 2021 by guest. Protected copyright. (CF) that is invaginated decreases with an increas- ability of corneal endothelial cells to synthesise within the endothelium and cornea to fluorescein which isfreefrom label. (London resin white x25 000.)

Figure 9 (a) Type III collagen labelling is intense and specifically localised to a bundle ofcollagenfibrils at the endothelialface of Descemet's membrane. The endothelial cytoplasm and posterior non-banded zone arefree oflabel. (b) Type V collagen labelling is also present over the posterior accumulation ofcollagen fibrils at the endothelialface ofDescemet's membrane. (London resin white (a) x30 000; (b) x24 000.) Corneal endothelial cellabnormalities in an early stage ofthe iridocorneal endothelial syndrome 631

the number of collagen types that are normally endothelium and Descemet's membrane in the irido-corneal endothelial syndrome. AmJ Ophthalmol 1986; 101: 16-27. not found in Descemet's membrane.'6 Bovine 8 Patel A, Kenyon KR, Hirst LW, Quigley HA, Stark WJ, corneal endothelial cells synthesise large Meyer RF, et al. Clinicopathologic features of Chandler's Br J Ophthalmol: first published as 10.1136/bjo.78.8.624 on 1 August 1994. Downloaded from syndrome. Surv Ophthalmol 1983; 27: 327-44. amounts of types I, III, and V collagen when 9 Alvarado JG, Murphy CG, Maglio M, Hetherington J. type III), Pathogenesis of Chandler's syndrome, essential iris atrophy grown in cell culture (predominantly and the Cogan-Reese syndrome. I. Alterations of the corneal whereas they synthesise types I and IV collagen endothelium. Invest Ophthalmol Vis Sci 1986; 27: 853-72. when cultured on their Descemet's membrane.2' 10 Kramer TR, Grossniklaus HE, Vigneswaran N, Waring GO, Kozarsky A. Cytokeratin expression in corneal endothelium It would appear that expression oftype I collagen in the iridocorneal endothelial syndrome. Invest Ophthalmol from that VisSci 1992; 33: 3581-5. synthesis has independent regulation 11 Eagle RC, Shields JA. Iridocorneal endothelial syndrome with ofIII and IV.2' Therefore it is not surprising that contralateral guttate endothelial dystrophy. Ophthalmology collagen types 1987; 94: 862-70. ICE endothelial cells synthesised 12 Hirst LW, Green WR, Luckenbach M, de la Cruz Z, Stark III and V without expression oftype I collagen. WJ. Epithelial characteristics of the endothelium in relevant to note that Chandler's syndrome. Invest Ophthalmol Vis Sci 1983; 24: It is certainly poly- 603-11. morphonuclear leucocyte cells can modulate the 13 Quigley HA, Forster RF. Histopathology ofthe cornea and iris of corneal endothelial cells by in Chandler's syndrome. Arch Ophthalmol 1978; 96: synthetic activity 1878-82. producing a corneal endothelial modulation 14 Marshall GE, Konstas AG, Lee WR. Immunogold fine transforms structural localisation of extracellular matrix components in factor (CEMF) that specifically aged human cornea. I Types I-IV collagen and laminin. normal type IV collagen synthesising endothelial GraefesArch Clin Exp Ophthalmol 1991; 229: 157-63. cells.2223 the 15 Marshall GE, Konstas AG, Lee WR. Immunogold cells to type I synthesising Since fine structural localisation of extracellular matrix com- inflammatory cells observed in this study and ponents in aged human cornea. II Collagen types V and VI. or Graefes Arch Clin Exp Ophthalmol 1991; 229: other studies were probably lymphocytes 164-71. macrophages this raises the interesting possi- 16 Marshall GE, Konstas AGP, Lee WR. Collagens in ocular cells can tissues. BrJ Ophthalmol 1993; 77: 515-24. bility that mononuclear inflammatory 17 Alvarado JA, Murphy CG, Juster RP, Hetherington J. produce similar CEMFs which can stimulate the Pathogenesis of Chandler's syndrome, essential iris an matrix. atrophy and the Cogan-Reese syndrome. II. Estimated age at ICE cells to produce abnormal disease onset. Invest Ophthalmol Vis Sci 1986; 27: 873-82. 18 Bahn CF, Falls HF, Varley GA, Meyer RF, Edelhauser HF, 1 Wilson MC, Shields MB. A comparison of the clinical Bourne WM. Classification of corneal endothelial disorders variations of the iridocorneal endothelial syndrome. Arch based on neural crest origin. Ophthalmology 1984; 91: Ophthalmol 1989; 107: 1465-8. 558-63. 2 Bourne WM. Partial corneal involvement in the iridocorneal 19 Bourne WM, Brubaker RF. Decreased endothelial endothelial syndrome. AmJ7 Ophthalmol 1982; 94: 774-81. perneability in the iridocorneal endothelial syndrome. 3 Hirst LW, Quigley HA, Stark WJ, Shields MB. Specular Ophthalmology 1982; 89: 591-5. microscopy of iridocorneal endothelial syndrome. Am J 20 Bourne WM, Brubaker RF. Progression and regression of Ophthalmol 1980; 89:11-21. partial corneal involvement in the iridocorneal endothelial 4 Laganowski HC, Sherrard ES, Kerr Muir MG, Buckley RJ. syndrome. AmJ Ophthalmol 1992; 114: 171-81. Distinguishing features of the iridocorneal endothelial 21 Kay EP, Oh S. Modulation of type III collagen synthesis in syndrome and posterior polymorphous dystrophy: value of bovine corneal endothelial cells. Invest Ophthalmol Vis Sci specular microscopy. Brj Ophthalmol 1991; 75: 212-6. 1988; 29: 200-7. 5 Sherrard ES, Frangoulis MA, Kerr Muir MG. On the 22 Kay EP, Ninomiya Y, Smith RE. Corneal endothelial modula- morphology of celis of the posterior cornea in the irido- tion: a factor released by leukocytes induces basic fibro- corneal endothelial syndrome. Cornea 1991; 10: 233-43. blastic growth factor that modulates cell shape and collagen. 6 Richardson TM. Corneal decompensation in Chandler's Invest Ophthalmol Vis Sci 1993; 34: 663-72. syndrome. A scanning and transmission electron micro- 23 Kay EP, Cheung CC, Chester JV, Nimni ME, Smith RE. http://bjo.bmj.com/ scopic study. Arch Ophthalmol 1979; 97: 2112-9. Type I collagen and fibronectin synthesis by retrocorneal 7 Rodrigues MM, Stulting RD, Waring GO. Clinical, electron fibrous membrane. Invest Ophthalmol Vis Sci 1982; 22: microscopic and immunohistochemical study of the corneal 200-12. on September 28, 2021 by guest. Protected copyright.