Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration

Sarit Y. Lesnik Oberstein, 1 Jiyun Byun, 3 Diego Herrera, 2 Ethan A. Chapin, 2 Steven K. Fisher, 2 Geoffrey P. Lewis 2
1 The Academic Medical Center Amsterdam, University of Amsterdam, The Netherlands;
2 Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California Santa Barbara, CA;
3 Mayachitra Inc., Santa Barbara, CA


Purpose: To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMs) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post-retinal detachment, and idiopathic ERM. Methods: Forty-six ERMs were removed from patients undergoing vitrectomy and immediately fixed in paraformaldehyde. The membranes were processed whole and immunolabeled with either anti-MIB-1 or anti-SP6 to detect the Ki-67 protein in proliferating cells, in combination with anti-glial fibrillary acidic protein or anti-vimentin to identify glia, anti-ezrin to identify retinal pigment epithelial cells, Ricinus communis to identify immune cells, and Hoechst to label nuclei. Digital images were collected using a laser scanning confocal microscope. The cell types were identified, their combined proliferative indices were tabulated as the average number of anti-Ki-67-positive cells/mm2 of tissue, and the number of dividing cells was related to the specific ocular condition and estimated disease duration. Results: ERMs of all four types were shown to be highly cellular and contained proliferating cells identified as glia, retinal pigment epithelium, and of immune origin. In general, membranes identified as PVR had many more Ki-67-positive cells in comparison to those in the other three categories, with the average number of Ki-67-positive cells identified per mm2 of tissue being 20.9 for proliferative diabetic retinopathy, 138.3 for PVR, 12.2 for post-retinal detachment, and 19.3 for idiopathic ERM. While all membrane types had dividing cells, their number was a relatively small fraction of the total number of cells present. Conclusions: The four ERM types studied demonstrated different cell types actively dividing at the time of removal, confirming that proliferation is a common event and does continue over many months. The low number of dividing cells at the time of removal in comparison to the total number of cells present, however, is an indicator that proliferation alone may not be responsible for the problems observed with the ERMs. Treatment strategies may need to take into consideration the timing of drug administration, as well as the contractile and possibly the inflammatory characteristics of the membranes to prevent the ensuing effects on the retina.
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Sarit Y. Lesnik Oberstein, Jiyun Byun, Diego Herrera, Ethan A. Chapin, Steven K. Fisher, Geoffrey P. Lewis,
Molecular Vision, vol. 17, pp. 1794-1805, Jul. 2011.
Node ID: 562 , DB ID: 371 , Lab: VRL , Target: Journal
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