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F.-L. Silver, G. Malek, P. Saloupis, S. J. McKinnon, S. W. Cousins; Recruitment of Blood-Derived Macrophages into the Inner Retina in Experimental Murine Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3085.
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New research indicates that blood-derived macrophages (rather than resident microglia) are recruited from the circulation and contribute to neurodegenerative diseases in the CNS as well as in the retina (including macular degeneration and diabetes). Their putative role as "good" or "bad" has yet to be established. We sought to determine if blood-derived macrophages were recruited into mouse eyes with experimental glaucoma.
Bone marrow chimeric mice were created by bone marrow transplantation of donor marrow from GFP-positive transgenic mice into wild type C57BL/6 recipients. After 1 month, all circulating leukocytes were GFP labeled. Elevated intraocular pressure was induced in 10 chimeric mice by the Morrison method of limbal injection of hypertonic saline into the episcleral vessels of the right eye. IOP was measured weekly in conscious mice using a TonoLab rebound tonometer. Additional mice received paracentesis or injection of PBS. Animals were observed for 4-8 weeks and tissue collected when the average change of IOP was greater than 200 mm-days. Retinal cross-sections and flatmounts were obtained and stained for GFP and F4/80, a macrophage specific marker, and examined by confocal microscopy.
In experimental eyes with elevated IOP, robust infiltration of GFP-positive macrophages was observed, confirming their recruitment from the circulation. Recruited macrophages tended to localize within the inner retina, especially within the inner plexiform layer and NFL. By flat mount, confocal microscopy demonstrated that these cells acquired dendritiform morphology, similar to the resident microglia. In contrast, neither unmanipulated fellow eyes, nor eyes of control animals receiving paracentesis or PBS injection, demonstrated significant infiltration of macrophages.
In experimental glaucoma, we demonstrate a significant infiltration of blood-derived macrophages into the inner retina. It is unclear whether these cells are recruited to scavenge debris after onset of RGC death, or conversely, that they play a causal role in promoting death of RGCs.
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