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G. P. Lewis, E. A. Chapin, G. Luna, K. H. Eibl, S. K. Fisher; The Role of Proliferating Mueller Cells in Subretinal Scar Formation Following Experimental Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5710.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the distribution of BrdU labeled Mueller cells following experimental retinal detachment (RD).
Experimental RDs were created in pigmented rabbit eyes and 10 micrograms of BrdU was injected intraocularly 3 days later. The retinas were harvested either 4 hr after the BrdU was injected (on day 3) or on day 7 or 10. The tissue was fixed, embedded in agarose and sectioned at 100 microns. The sections were then labeled with 3 probes: anti-BrdU was used to detect the BrdU labeled dividing cells, anti-vimentin was used to label Mueller cells, and the Isolectin B4 was used to identify macrophages and microglia. Their distribution was determined using an Olympus FluoView confocal microscope.
Three days after detachment, many vimentin labeled Mueller cells were also labeled with BrdU and their nuclei resided in their normal location in the inner nuclear layer (INL). At day 7 and 10, three patterns in the distribution of BrdU labeled Mueller cell nuclei were observed depending on the extent of glial reactivity: 1) In the least reactive state, the retina often contained BrdU labeled Mueller cell nuclei in columns with one labeled nucleus in the INL and another directly sclerad to it in the outer nuclear layer (ONL). 2) In areas showing extensive glial hypertrophy within the retina, many BrdU labeled nuclei were scattered throughout the INL and ONL. 3) In regions that had progressed to forming a subretinal glial scar, much of the retina was devoid of BrdU labeled nuclei, however, many BrdU positive nuclei were now present in a subretinal glial scar. Isolectin B4 labeled cells also incorporated BrdU and were observed throughout the retina and subretinal scar during all phases of detachment.
Following RD, BrdU labeled Mueller cell nuclei initially lie in their normal location in the INL, then form a columnar pattern, invariably migrating towards the outer retina, with many eventually ending up in a subretinal glial scar. Our data raise the possibility that it is the dividing Mueller cells that are responsible for producing subretinal fibrosis, a condition that may be under-appreciated in human patients because of the difficulty in visualizing the thin layer of Mueller cell processes in the subretinal space. In animal models of reattachment, a single layer of Mueller cell cytoplasm is sufficient to block outer segment regeneration. Inhibition of proliferation during the early phase of detachment may prevent the eventual formation of subretinal glial scars.
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