Exp. Eye Res. (1991) 53. 275-281

Retinal MICHAEL

Microglia: WELLER”,

University

PETER

A New Cell in Idiopathic Vitreoretinopathy? ESSER,

KLAUS

HEIMANN

Proliferative

AND PETER

WIEDEMANNt

Eye Hospital, Joseph- Stekmann - Strasse 9, 5000 Cologne 4 7, Germany

(Received 24 September

7990 and accepted in revised form 28 November

1990)

Despite numerous studies of the role of mononuclear phagocytes in proliferative vitreoretinopathy. the origin of these cells has remained obscure. Notably, retinal microglial cells have consistently been neglected. Applying double label immunohistology with a set of new cell markers to 37 preretinal traction membranes, we have identified a distinct population of proliferating cells presumably of microglial origin. The identification of microglia relies on positive labels for LN-I, Ricinus communis agglutinin-I, vimentin. HLA-DR. and nucleoside diphosphatase. and negative labels for Leu-Ml ) Leu-M 3, EBM-11, von Willebrand factor. CD22, cytokeratin, and glial fibrillary acidic protein. Microglia are much more prevalent in idiopathic than in traumatic proliferative vitreoretinopathy and insignificant in proliferative diabetic retinopathy. HLA-DR expression was not restricted to pigment epithelium as previously reported but also observed in microglia, macrophages, endothelial and glial cells. The detection of retinal microglial cell proliferation suggestsa pathogenetic role of these cells and questionscurrent conceptsof the cellular biology of proliferative vitreoretinopathy. Key words: proliferative vitreoretinopathy ; microglia : macrophages; immunochemistry: LN- 1. 1. Introduction

Proliferative vitreoretinopathy is a multi-stage disease process at the vitreoretinal interface reminiscent of physiologic wound healing (Weller, Wiedemann and Heimann, 1990). The contraction of periretinal cellular membranes leads to traction retinal detachment and is a major contributor to failure of vitreoretinal surgery (The Retina Society Terminology Committee, 1983). An idiopathic form develops following rhegmatogenous retinal detachment while the majority of cases are post-traumatic and complicate perforating eye injuries and previous vitreoretinal surgery. Experimental and clinical studies have confirmed an important role for mononuclear phagocytes in the pathogenesis of proliferative vitreoretinopathy (Miller et al., 1986; Pollack et al., 1986; Burke and Twining, 1987; Weller, Heimann and Wiedemann, 1988b). Although the issue of different sources for macrophages in retinal wound healing was raised as early as 1933 (Gray, 1933), numerous morphological and immunocytochemical studies have so far failed to determine precisely the origin of phagocytosing cells in proliferative vitreoretinopathy (Gloor, 19 74 ; Kampik et al., 1981 ; Hiscott, Grierson and McLeod, 1985 : Jerdan et al., 1987: Schwarz et al., 1988; Weller, Heimann and Wiedemann. 1988a; Jerdan et al., 1989). The current double label immunofluorescence study tries to clarify this issue by using a set of cell markers (Table I) most of which have never been applied to * Current address: Department

of Neurology, University of Tiibingen. Hoppe-Seyler-Str. 3, 7400 Tiibingen, Germany. t For correspondence at: University Eye Hospital. Joseph-Stelzmann-Strasse 9. 5000 Cologne 41, Germany.

00144835/Y1/080275+07

$03.00/O

surgically obtained preretinal traction membranes. Specifically, we present a new strategy to identify retinal microglial cells by means of a distinct pattern of antibody reactivity. 2. Materials and Methods

Preretinal Membranes We examined preretinal membranes from patients with idiopathic (n = IO) and traumatic (n = 12) proliferative vitreoretinopathy and proliferative diabetic retinopathy (n = 15). Traumatic proliferative vitreoretinopathy includes cases of previous perforating trauma as well as previous vitrectomy for rhegmatogenous retinal detachment. The techniques of sample collection, sample processing, preparation of slides, immunostaining, positive and negative controls, and photomicrographic documentation have been presented previously (Weller, Heimann and Wiedemann, 1989). Preretinal membranes were dipped in isopentane ( - 50°C) immediately after vitreoretinal surgery and stored at - 70°C until preparation of 8-lo-pm cryostat sections. Antibodies

Primary antibodies for the characterization of different cell populations (Table I) were Leu-Ml /CD1 5 and Leu-M3/CD14 (1: 100; Becton Dickinson, Mountain View, CA), LN-1 (undiluted: Biotest, Dreieich, Germany), 0X-42, ED2 (I : 100 : Serotec. Camon, Wiesbaden, Germany), anti-human

macrophage EBM-

11 (1:40), anti-human HLA class I (1: loo), antihuman HLA-DR alpha chain (1: loo), anti-human complement C3b receptor/CD3 5 (I : 30 1.anti-human 0 199 I Academic Press Limited

M. WELLER

276 TABLE I

Target antigens for the characterization of‘ mononuclear phagocytes and microglial cells in preretinal traction membranes. Leu indicates leukocyte antigen. CD numbers are ‘cluster of diflerentiation numbers’ according to the international Workshops of Leucocyte Diterentiation Antigens. EBM-2 1 and LN-1 are pharmaceutical cornpang codes, e.g. indicating clones. HLA, Jormerly ‘human leukocyte antigen’, is the human major histocompatibility complex (MHC) on chromosome 6. Antigen ~~ ._ _Leu-Ml/CD15

Leu-M3/CD14 Complement C3b receptor/CD3 5 EBM-11 HLA-DR

LN- 1 B-cell CD22 Antichymotrypsin Ricinus communis agglutinin- 1 Von Willebrand factor Glial fibrillary acidic protein Cytokeratin

Target cells Monocytes, polymorphonuclear granulocytes. (Macrophages, histiocytes) Monocytes. macrophages Reticulum cells (monocytes, Blymphocytes. epithelial cells) Macrophages Lymphocytes, macrophages, astrocytes retinal pigment epithelial cells, microglia B-Lymphocytes, epithelial cells, microglia B-Lymphocytes Histiocytes Microglia. macrophages, endothelial cells Vascular endothelial cells Glial cells [Pigmented) epithelial cells

a,-antichymotrypsin (1: loo), anti-von Willebrand factor (1: loo), anti-B-cell CD22 (1: 50), anti-human glial fibrillary acidic protein (1: 50). anti-cytokeratin ( 1: 100). and anti-vimentin (1: 50) (all Dakopatts, Copenhagen, Denmark), and anti-interferon gamma (undiluted, Endogen, Boston, MA). Staining Protocols and Controls Immunodetection systems were double label immunofluorescence. peroxidase, and phosphatase techniques using biotinylated sheep anti-mouse IgG and phycoerythrin-streptavidin complex. fluorescein-antirabbit IgG (all Amersham, U.K.), streptavidin-alkaline phosphatase (Dakopatts), anti-mouse IgM and antimouse and anti-sheep IgG alkaline phosphatase (Sigma). Peroxidase and phosphatase substrates were obtained from Sigma.

ET AL.

For quantification of cellular subgroups. c.g. ratio of Leu-Ml positive cells among EBM-11 positive cells (see below), all cells of a given slice were counted without technical devices. Double label immunofluorescence studies were performed combining LN-1 and several other antibodies. This was possible because LN-1 was the only IgM mouse antibody. Therefore, no interference of detection systems was to be expected. Specificity of primary antibody binding was confirmed by substitution of primary antibody with nonimmune IgG of the same animal species that supplied the antibody proper. In addition, exchange of detection systems was performed prior to double label experiments to exclude cross recognition of primary antibodies and detection systems. Human brain hippocampal sections were used as a positive control for LN-1. GFAP, and Ricinus communis agglutinin type 1, Monocyte/macrophage and lymphocyte cell smears as positive control for leukocyte markers were prepared according to Freundlich and Avdalovic (1983).

Microglial cells were also visualized by modified Iectin cytochemistry (Mannoji, Yeger and Becker, 1986: Suzuki et al., 1988) using rhodamine-conjugated Ricinus communis agglutinin type I (Sigma: 5 mg 1-l) and nucleoside diphosphatase activity (Murabe and Sano. 1982; Terubayashi et al., 1984). Specificity of lectin binding was confirmed by addition of increasing amounts of lactose (Mannoji et al., 1986). Strutegg fbr Identification of Microglial Cells

First, microglial cells have to be labeled by LN-1 but not by the B-lymphocyte marker, anti-CD-22. to prove that these cells could be microglial cells (Miles and Chou, 1988) but are certainly not B-lymphocytes (as LN- 1 is a B-lymphocyte marker ). Second, microglial cells should be stained with Ricinus communis agglutinin- 1. This lectin, however, recognizes microglial cells and most other cells of the mononuclear phagocyte system as well as endothelial cells. Therefore. the putative microglial cells must not react with anti-von Willebrand factor antibody, an endothelial marker, and conventional macrophage markers such as EBM-11, Leu-Ml. and Leu-M3. Third, analysis of intermediate filament expression should yield positive staining for vimentin, the filament of activated microglia, but not for the glial marker. glial fibrillary acidic protein, and the epithelial marker, cytokeratin. HLA expression does not contribute to the identification of any particular cell type but was examined to estimate the participation of different cell types to the whole population of HLA expressing cells.

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TABLE II Ratio between antigen-positive membranes and total number of membranes examined for different antigens in idiopathic and traumatic proliferative vitreoretinopathy and proliferative diabetic retinopathy.

.-. ~- ~~ -

___ “LN-1 * Ricinus comm. agglutinin- 1 * HLA-ABC * HLA-DR * Vimentin f-CD22 “rEBM-11 t Leu-Ml/CD15 tLeu-M3/CD14 t C3bRec./CD3 t Cytokeratin t Glial fibrillary acidic protein f von Willebrand factor t a,-Antichymotrypsin

Idiopathic proliferative vitreoretinopathy

Traumatic proliferative vitreoretinopathy _

Proliferative diabetic retinopathy

1O:lO 10: IO

7: 12 12:12

2:15 15:15

8:8 8:8

8:8 8:8

8:8 8:8

1O:lO

12:12

15:15

0:7 0:7

0:8 11:12 fi:9 8:9 2:9

0:7 0:7 0:7 0:7 0:7

1:7 0:7 0:7 3:6 6:6

9:lO

5:lO

2:lO

6:IO

0:6

2:8

9:9

4:8

9:9

4:9

* Indicates positive markers which indicate that a cell may be of microglial origin. ; Indicates negative markers which exclude a microglial origin of a given cell. The diffuse pattern of chymotrypsin reactivity precludes any conclusions with regard to microglial cells.

FIG. 1. Diffuse intense immunofluorescence for antichymotrypsin in traumatic proliferative vitreoretinopathy. Cell nuclei are visible as dark round structures. A differentiation between extracellular matrix and perinuclear space, i.e. cytoplasm, is impossible. This pattern could indicate cellular secretion or, alternatively. diffusion of the protein from the intracellular space during the process of fixation. x 2 19.

M. WELLER

ET AL.

FIG. 2. Rhodamine-conjugated Ricinus communis agglutinin-1 labels microglial cells in idiopathic proliferative vitreoretinopathy. No EBM-11-positive or von Willebrand factor-positive cells were found in this specimen. confirming a microglial origin of the stained cells. x 219.

FIG. 3. Imiml unofluorescence 1abelIngof blood vessel endothelium (solid arrow) and a solitary microglial cell Ipen a identifi led on P’arallel section by LN-1 staining, recognized by Ricinus communis agglutinin-1. x 550. 3. Results Ratios of positive specimens vs. total specimens examined for single antigens are provided in Table II. We observed few Leu-Ml and Leu-M3 positive cells in traumatic, and almost none in idiopathic, proliferative vitreoretinopathy. Leu-Ml and Leu-M3 labeled almost identical cell populations but only a third of those cells identified as macrophages by EBM-11. The anti-a,antichymotrypsin staining pattern was diffuse and

much less confined to cells than other cell markers (Fig. 1). The complement C3b-receptor was labeled only on a very few Leu-M3 and Leu-M5 positive cells in two cases of traumatic proliferative vitreoretinopathy. HLA-ABC (Class I) antigens were uniformly present on all cells while HLA-DR was expressed by all Leu-M3 and Leu-M 5 positive cells (mononuclear phagocytes ), all von Willebrand factor-positive cells (endothelial cells), almost half of cytokeratin-positive cells (retinal

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279

FIG. 4. Phosphatase immunolabeling using I&l shows microglial proliferation in idiopathic proliferative vitreoretinopathy. Approximately 30 cells can be recognized. Phosphatase conversion of a colourless substrate yields a bright red product which appears dark on this photograph. Counterstaining with hematoxyline shows the structure of the extracellular matrix. x 550.

pigment epithelial cells), a few glial fibrillary acidic protein positive cells (glia), and a distinct cell group positive for LN- 1. Lectin cytochemistry using Ricinus communis agglutinin- 1 delineated three cell populations, one identical with LN-1 positive (putative microglial) cells, one compatible with EBM-1 l-reactive macrophages, and another which was easily identified as vascular endothelium using both routine stains and anti-von Willebrand factor antibody (Mannoji et al., 1986). In proliferative vitreoretinopathy, Ricinus communis agglutinin-1 labeled EBM-11 positive macrophages and LN-1 positive cells (Fig. 2). In diabetic retinopathy, Ricinus communis agglutinin-1 bound to vascular endothelial cells predominantly and to some LN-1 positive cells (Fig. 3). In idiopathic proliferative vitreoretinopathy, LN-1 positive cells were observed mostly in clusters and represented from 10 to 60 ‘% of all vimentin positive cells (Fig. 4). Most of them had a fibroblastic appearance on routine stains. LN-l-positive cells were scarce in traumatic proliferative vitreoretinopathy although they were detected in 7 out of 12 membranes (Table II). They were always less numerous than EBM11 positive macrophages and never reached 10% of total cell counts. Interferon gamma and B-cell antigen CD22 were not detected in any of the specimens.

4. Discussion The identification of retinal microglial cells, previously neglected in vitreoretinal pathology studies, in traction membranes from patients with proliferative

vitreoretinopathy changes previous concepts of the cellular pathobiology of this disease. The mononuclear phagocyte system comprises different cell populations including monocytes, macrophages, microglial cells, hyalocytes, and the phagocytes formerly designated as tissue histiocytes or the reticuloendothelial system (Johnston, 1988). Owing to specialized barriers between blood and nervous tissue, both brain and retina are privileged sites immunologically. Two major issues have dominated the study of brain and retinal phagocytes (Streit, Graeber and Kreutzberg, 1988; Jordan and Thomas, 1988). First, do all resident brain and retinal phagocytes stem from peripheral blood monocytes which invade brain and retina during embryonic development (Perry and Gordon, 1988) or are they highly specialized glial cells (Miles and Chou, 1988)? Second, what is the relative contribution of resident vs. hematogenously derived phagocytes to wound healing and tissue repair in lesioned adult brain and retina (Schelper and Adrian, 1986)? Answers to these questions are not only relevant to cellular biology but will influence further pharmacological approaches for the prevention of traction retinal detachment. Initial support for the hypothesis of microglial involvement in proliferative vitreoretinopathy was obtained by application of LN-1 antibody, an established B-lymphocyte marker recently reported to label human microglial cells (Miles and Chou, 1988; Dickson and Mattiace, 1989). Negative label with the B-lymphocyte marker, CD22, excluded that LN-1 positive cells in the specimens were B-lymphocytes. In addition, these cells stained positive with Ricinus communis agglutinin- 1, vimentin, HLA-DR. and

M. WELLER

280

nucleoside phosphatase but negative with EBM-11, anti-gliaI librillary acidic protein, cytokeratin, and von Willebrand factor, a pattern suggestive of microglia. The significance of the antigen recognized by LN-1 is unknown but reactivity with multiple other cells, all of which are completely unrelated to ophthalmology with the exception of astrocytes (Dickson and Mattiace, 1989), has been reported (Epstein et al., 1984). The expression of a lymphocyte marker suggestsa specific immunologic function of microglial cells and provides evidence against their derivation from monocytes/macrophages (Miles and Chou, 1988). Microglia seemsto be the major phagocytosing cell in idiopathic proliferative vitreoretinopathy but does not play a role In proliferative diabetic retinopathy. Blood-borne mononuclear phagocytes and only a small population of microglial cells appear to be involved in traumatic proliferative vitreoretinopathy (Table II). Part of HLA-DR positive cells were cytokeratinnegative (i.e. not pigment epithelial cells) and glial fibrillary acidic protein-negative (i.e. not glial cells) but positive for the intermediate filament vimentin, the characteristic cytoskeletal filament protein of activated but not quiescent microglia (Graeber, Streit and Kreutzberg, 1988). This HLA-DR expression by microglial cells has also been documented in neuroinflammatory disorders (Frei et al., 1987; Fontana et al., 1987) and is certainly not a specific feature of proliferative vitreoretinopathy. HLA-DR expression was not restricted to pigment epithelial cells (Baudouin et al., 1988, 1989, 1990; Jerdan et al., 1989) glial cells, and presumed microglia,

but also detected, less frequently,

on

vascular endothelial cells. One earlier study (Baudouin et al., 1989) did not provide information

about the

means of pigment epithelial cell identification, e.g. cytokeratin labeling as performed by Jerdan et al. ( 19 89) and in this study. Jerdan and associates( 19 89) found colocalization of HLA-DR and cytokeratin but not of Leu-M3 and HLA-DR and suggested retinal pigment epithelial cells as major class II presenting cells in proliferative vitreoretinopathy. We observed HLA-DR expression by Leu-M3, Leu-M 5, and EBM-llpositive phagocytes consistently while only about half of the abundant retinal pigment epithelial cells were

HLA-DR positive. Interferon gamma is a potent stimulus for HLA-DR expression. Our inability to label interferon gamma, or

lymphocytes as a significant source of interferon, in preretinal membranes (Weller et al., 1988 b ; Jerdan et al.. 1989). should direct further attention to alternative inducers of HLA class II presentation. Recent studies suggest a role for immune-mediated events both in proliferative vitreoretinopathy and in proliferative diabetic retinopathy (Baudouin et al.,

1988. 1989, 1990). The identification of microglial cells expressing both LN- 1, a B-lymphocyte activation marker, and HLA-DR antigens supports their findings

ET AL.

but shifts emphasis from a humoral immune response characterized by complement activation (Baudouin et

al., 19 89) to local immunoregulation in retinal tissues. The biochemical stimuli for microglial proliferation in idiopathic proliferative vitreoretinopathy remain to be determined but astrocyte-derived interleukin- 3 appears to be a likely candidate (Frei et al., 1986). If a pathogenetic role of retinal microglia in proliferative vitreoretinopathy is accepted, more in vitro data on microglial cells (Rieske et al., 1989) are needed to improve the pharmacologic treatment of the disease. Acknowledgements

This study was supported by the Retinovit-Foundation and DFG-(DeutscheForschungs-Gemeinschaft)Grant Wi 880/3-l to P.W. References Baudouin. C., Fredj-Reygrobellet. D., Baudouin, F.. Lapalus, P. and Gastaud. P. (1988). Immunohistopathological findings in proliferative diabetic retinopathy. Am. J. OpktkaZmol.105, 38 3-7. Baudouin. C.. Fredj-Reygrobellet, D., Baudouin, F.. Lapalus. P. and Gastaud, P. (1989). Immunohistologic study of proliferative vitreoretinopathy. Am. 1. Opktknlmol. 108, 387-94. Baudouin, C., Gordon, W. C., Fredj-Reygrobellet, D., Baudouin. F., Peyman, G., Gastaud. P. and Bazan, N. G. ( 1990). ClassII antigen expression in diabetic preretinal membranes. Am. 1. Opktkalmol. 109. 70-4. Burke, J. M. and Twining, S. S. (198 7). Vitreous macrophage elicitation: generation of stimulants for pigment epithelium in vitro. Invest. Opktkalmol. Vis. Sci. 28. 1100-7.

Dickson, D. W. and Mattiace. L. A. (1989). Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocyte-specific monoclonal antibody. Am. 1, F’utkol. 135, 13547.

Epstein, A. L., Marder, R. J.. Winter. J. N. and Fox, R. I. (1984). Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embeddedtissues with follicular center and mantle zone human Blymphocytes and derived tumors. 1. Immunol. 133, 1028-36. Fontana. A., Frei, K., Bodmer. S. and Hofer, E. (1987). Immune-mediated encephalitis : on the role of antigenpresenting cells in brain tissue. Jmmunol. Rev. 100, 185-201. Frei. K., Bodmer. S.. Schwerdel, C. and Fontana, A. (1986). Astrocyte-derived interleukin 3 as a growth factor for microglial cells and peritoneal macrophages.I. Immunol. 137,

3521-7.

Frei, K., Siepl, C., Groscurth, P., Bodmer. S., Schwerdel, C. and Fontana, A. (1987). Antigen presentation and tumor cytotoxicity by interferon-H-treated microglial cells. Eur. 7. Immunol. 17, 1271-8. Freundlich. B. and Avdalovic. N. ( 198 3). l&e of gelatin/ plasma coated flasks for isolating human peripheral blood monocytes. 1. Immunol. Methods 62. 31-7. Gloor. B. P. (1974). On the question of the origin of macrophages in the retina and the vitreous following photocoagulation. Autoradiographic investigations by means of 3H-thymidine. Graefe’s Arch. Clin. Exp. Opktkafmol. 190, 183-94.

RETINAL

MICROGLIA

Graeber, M. B., Streit. W. J. and Kreutzberg. G. W. (1988). The microglial cytoskeleton : vimentin is localized within activated cells in situ. J. Neurocytol. 17, 573-80. Gray, W. A. (1933). Cellular response of vitreous humour to injections of bacteria, blood and vital dyes. 1. ~uthol. Bacterial. 37. 137-48. Hiscott, P. S., Grierson, I. and McLeod, D. (1985). Natural history of fibrocellular epiretinal membranes: a quantitative. autoradiographic, and immunohistochemical study. Br. J. Ophthalmol. 69, 810-23. Jerdan, J. A.. Pepose. J.. Maglione, A., Michels, R. G. and Glaser. B. M. (1987). PVR membranes-an immunohistological study. Invest. Ophthalmol. Vis. Sci. 28. 115 (SUPPI.1. Jerdan. J. A.. Pepose, J. S.. Michels, R. G., Hayashi. H., De Bustros. S.. Sebag. M. and Glaser, B. M. (1989). Proliferative vitreoretinopathy membranes. Ophthalmology 96, 801-10. Johnston, K. B. (1988). Monocytes and macrophages. N. Engl. J. Med. 318, 747-52. Jordan. F. L. and Thomas, W. C. (1988). Brain macrophages : questions of origin and interrelationship. Bruin Research Reviews 13. 165-78. Kampik, A.. Kenyon. K. R.. Michels, R. G.. Green, W. R. and de la Cruz, Z. C. (1981). Epiretinal and vitreous membranes. Comparative study of 56 cases. Arch. Ophthabnol. 99, 1445-54. Mannoji. H.. Yeger. H. and Becker, L. E. (1986). A specific histochemical marker (lectin Ricinus communis agglutinin-1 ) for normal human microglia, and application to routine histopathology. Acta Neuropathol. (Bed.) 71. 341-3. Miles. J. M. and Chou, S. M. (1988). A new immunoperoxidase marker for microglia in paraffin section. J. Neuropathol. Exp. Neural. 47, 579-87. Miller. B., Miller, H., Patterson, R. and Ryan, S. J. (1986). Retinal wound healing. Cellular activity at the vitreoretinal interface. Arch. Opphthalmol. 104, 281-5. Murabe. Y. and Sano, Y. (1982). Morphological studies on neuroglia. V. Microglial cells in the cerebral cortex of the rat, with special reference to their possible involvement in synaptic function. Crll Tiss. Res. 223. 49 3-506. Perry, V. H. and Gordon. S. (1988). Macrophages and microglia in the nervous system. Trends Neurosci. 11, 273-7. Pollack. A., Korte, G. E.. Heriot, W. J. and Henkind. P. (1986). Ultrastructure of Bruch’s membrane after krypton laser photocoagulation. II. Repair of Bruch’s

281

membrane and the role of macrophages. Arch. Ophthalmol. 104, 1377-82. The Retina Society Terminology Committee ( 1983). The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90, 121-5. Rieske, E.. Graeber, M. B., Tetzlaff, W., Czlonkowska. A., Streit, W. J. and Kreutzberg, G. W. (1989). Microglia and microglia-derived brain macrophages in culture : generation from axotomized rat facial nuclei. identification and characterization in vitro. Brain Res. 492, I-14. Schelper, R. L. and Adrian, E. K. (1986). Monocytes become macrophages: they do not become microglia: a light and electron microscopic autoradiographic study using 12 5-iododeoxyuridine. 1. Neuropthol. Exp. Neurol. 45, l-19. Schwartz. D.. de la Cruz. 2. C., Green, W. R. and Michels, R. G. (1988). Proliferative vitreoretinopathy. Ultrastructural study of 20 retroretinal membranes removed by vitreous surgery. Retina 8. 275-81. Streit, W. J., Graeber, M. B. and Kreutzberg. G. W. (1988). Functional plasticity of microglia: a review. Glia 1, 301-7. Suzuki, H.. Franz, H., Yamamoto, T.. Iwasaki, Y. and Konno, H. (1988). Identification of the normal microglial population in human and rodent nervous tissue using lectin-histochemistry. Neuropathol, Appl. Neurobiol. 14, 221-7. Terubayashi, H., Murabe. Y.. Fujisawa, H., Itoi. M. and Ibata. Y. (1984). Enzymhistochemical identification of microglial cells in the rat retina: light and electron microscopic studies. Exp. Eye Res. 39, 595-603. Weller, M., Heimann, K. and Wiedemann, P. (1988a). Demonstration of mononuclear phagocytes in a human epiretinal membrane using a monoclonal anti-human macrophage antibody. Graefe’s Arch. Clin. Exp. Ophthulrnol. 226, 252-4. Weller, M.. Heimann, K. and Wiedemann, P. (1988b). Immunochemical studies of epiretinal membranes using APAAP complexes. Evidence for macrophage involvement in traumatic proliferative vitreoretinopathy. ht. Ophthalrnol. 11, 181-6. Weller, M.. Heimann. K. and Wiedemann. P. (1989). Immunochemical analysis of periretinal membranes. Review and outlook. Dev. Ophthalmol. 16, 54-74. Weller. M.. Wiedemann, P. and Heimann, K. (1990). Proliferative vitreoretinopathy-is it anything more than wound healing at the wrong place! Int. Ophthalmal. 14, 105-l 7.

Retinal microglia: a new cell in idiopathic proliferative vitreoretinopathy?

Despite numerous studies of the role of mononuclear phagocytes in proliferative vitreoretinopathy, the origin of these cells has remained obscure. Not...
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