Abstract
Abstract: :
Purpose:Transgenic mice, in which PDGF-B is overexpressed in the photoreceptors, develop a cell mass in the inner retina, which is comprised of endothelial cells, glia, and pericytes. Double-labeling using proliferating cell nuclear antigen (PCNA) with markers to identify these cell types was used to distinguish the proliferative fractions of each cell type during the development of the cell mass. Methods: Paraffin sections of retinas from transgenic mice were double-labeled for PCNA (to label proliferating cells) in combination with glial fibrillary acidic protein (glial cell marker), Griffonia simplicifolia isolectin-B4 (endothelial cell marker), or smooth muscle actin (pericyte marker). Results: Pathological cell proliferation is not evident at postnatal day 5 (P5), but at P7, it originates along the inner edge of the ganglion cell layer (GCL), sometimes extending to the inner edge of the inner nuclear layer (INL). Double-labeling reveals that this highly proliferative layer is primarily composed of endothelial cells. Glial cells, at this time point, are limited to the inner surface of the retina, and have a lower proliferative index. Few pericytes are present at this time and are primarily found beneath the glial cells. By P9-10, all 3 cell types have dispersed through the expanding cell mass and are highly proliferative. Some endothelial cells have migrated into the retina or broken through the inner limiting membrane. The proliferative cell fraction decreases beyond P14. Conclusion: In PDGF-B transgenic mice, abnormal cell proliferation begins at P7. The most proliferative cell fraction at the onset consists of endothelial cells, which align themselves in the area from the inner edge of the GCL to the INL. Glial cells proliferate and spread along the retinal surface with pericytes accumulating beneath them. All 3 cell types proliferate and spread throughout the cell mass as it thickens, with endothelial cells leading the penetration into the retina. Cellular proliferation reaches a peak at P14 in this model.
Keywords: 483 neovascularization • 523 proliferation • 423 growth factors/growth factor receptors