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Chandrika Abburi, Adam Cantor, Sergio Caballero, Raj Maturi, Timothy Kern, Maria Grant, Keith March, Gangaraju Rajashekhar; Therapeutic Efficacy of Adipose Stromal Cells to Protect the Retinal Neurons and Vasculature in Rat Retinal Ischemia-reperfusion Injury Model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4612.
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© ARVO (1962-2015); The Authors (2016-present)
Ischemia-reperfusion (I/R) injury in eye is known to cause retinal neurodegeneration and retinal capillary degeneration associated with inflammation and apoptosis. In this study, we tested if adipose stromal cells (ASC) can protect retinal damage in a rat model of I/R injury.
Unilateral retinal I/R was induced in 32 adult Lewis rats by cannulating the anterior chamber of the globe and transiently elevating the intraocular pressure for 2h. Untreated eyes served as I/R controls. After day 7 of reperfusion the animals were randomized to receive intravitreal ASC (GFP labeled, 50,000 cells) or saline injections. After further 6-7 days, retinal function was assessed by Electroretinogram (ERG), histological changes by light microscopy and integration of ASC into host vasculature by confocal microscopy.
I/R resulted in a significant reduction in “b” wave amplitude (as measured by electroretinogram) compared to anesthetized live un-injured control rats, and this I/R induced reduction was significantly improved by ASC at day-6 post injection (93±12 v/s 122±6 μvolts, p<0.05; n=6). Subsequently, retinal histological analyses at day-7 revealed an increase in retinal thickness (118±6 v/s 289±9μm, p<0.001; n=5); decrease in gliosis as measured by expression of glial fibrillary acidic protein (GFAP; 50±9 v/s 12±2 RFU/sq.mm, p<0.001, n=5) and decrease in apoptosis (146±25 v/s 59±6 RFU/sq.mm, p<0.001, n=5) as measured by Caspase-3 staining in retina from injured eyes received ASC compared to injured eyes received saline. Furthermore, ASC injected into eyes with I/R associated specifically with damaged areas of the vasculature compared to control group that received ASC (273,682±91,853 v/s 77,619±25,383 mean GFP/μm3 of retina).
Our findings suggest that ASC improves the function of retina and rescues I/R injury induced retinal degeneration. Although more studies are warranted to understand the therapeutic potential of ASC, our data suggests that ASC assimilate with the host vasculature to stabilize vessels and can also decrease neuronal apoptosis.
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