Abstract
Abstract: :
Purpose: In development, glial cells guide the formation of new blood vessels. This study investigated whether glial cells guide the formation of new blood vessels in the light–damaged retina. Methods: Male Wistar rats were exposed to bright–white light (10K Lux) for 3hrs and then maintained on a 12hr light/dark cycle in a normal animal house lighting conditions for 24 hours to 4 months. Eyes were fixed with 4% paraformaldehyde for 1 hour and embedded in paraffin wax. Sections were immunolabelled for the glial cell markers GLAST and GFAP, and for the Na+/H+ exchanger regulatory factor (NHERF2), which is expressed by endothelial cells and precursors thereof. Results: We demonstrate that in the normal eye, NHERF2 is expressed by vascular endothelial cells in the choroid and inner retina. After light damage, NHERF2 is expressed in columns of cells aligned along radial Müller cell processes, these columns appear to represent precursors of blood vessels. New vessels that form in the outer retina appear to be derived from inner retinal elements, as evinced by their continuity with inner retinal blood vessels. They do not appear to derive initially from the choroidal vasculature, as Bruchâ€TMs membrane remains intact at this initial stage. We suggest that newly forming vessels appear to use remodelled Müller cell processes as guidance templates, allowing blood vessels in the inner retina to extend into the outer retina, and ultimately to connect to the choroidal vasculature. Conclusions: Glial cells play a significant role in the guidance of new blood vessel formation in response to light damage. This contrasts with the assumption, in diseases such as AMD, that vessel formation is initiated in the choroid and that vessels enter the retina via breaks in Bruch's membrane and the RPE. Our data suggest the causal stimulus of neovascularisation in response to light damage may initially affect elements in the inner retina rather than in the outer retina/ choroid/ RPE. We suggest that pharmacological manipulation of the glia–endothelial interaction may be a useful strategy in modifying blood vessel formation in such disease states.
Keywords: retinal degenerations: cell biology • vascular cells • Muller cells