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R.F. Gariano, E. Aguilar, M. Friedlander; Endothelial Proliferation in Human Retinal Diabetic Microaneurysms . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2253.
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Purpose: Microaneurysms may arise via mechanical weakening and distention of the vessel wall, or by proliferation of endothelial cells. We evaluated the latter mechanism by assessing proliferative activity of cells comprising diabetic microaneurysms. Methods: Eyes were obtained within 12 hours of death from three patients with diabetes mellitus. Retinopathy was determined by inspection of bisected globes using a dissection microscope. Retinas were processed for fluorescence immunohistochemistry, using lectin Ulex europaeous to label vascular endothelial cells, and antibodies to smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and Ki67 to label pericytes, astrocytes, and proliferating cells, respectively. Retinal flatmounts and frozen sections were examined by confocal fluorescence microscopy. Results: All retinas exhibited signs of non-proliferative diabetic retinopathy, including dot and blot hemorrhage, cotton wool spots, and areas of capillary non-perfusion. Microanuerysms in all retinas appeared as spherical or nearly spherical clusters of endothelial cells continuous with capillary segments. Pericyte and astrocyte immunoreactivity in the vicinity of aneurysms was similar to that near capillaries without aneurysms. Ki67-positive nuclei were evident in most microaneurysms; many of these proliferating cells also labeled with Ulex, and were seen on cross-sections to be within the wall of the microaneurysm. Occasional proliferating cells were noted surrounding microaneurysms, but these cells did not bind Ulex or exhibit GFAP or SMA immunoreactivity. Endothelial proliferation in blood vessel walls outside of microaneurysms was rare. Conclusions: Endothelial cell proliferation may contribute to formation of microaneurysms in non-proliferative diabetic retinopathy. These results are consistent with the involvement of endothelial cell mitogens, such as vascular endothelial growth factor, in early retinopathy. The identity of prolfierating cells surrounding microaneurysms is under investigation.
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