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Gavin W. Roddy, Robert H. Rosa, Jr., Matthew M. LaVail, Michael T. Matthes, Douglas Yasumura, Joo Youn Oh, Darwin J. Prockop; Intravitreal Administration Of Adult Stem/progenitor Cells And Their Secreted Proteins Delays Retinal Degeneration By Decreasing Apoptosis In Two Rat Models. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2218.
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Therapeutic benefits have been observed with administration of adult stem/progenitor cells from bone marrow (mesenchymal stem cells, or MSCs). MSCs may engraft and differentiate to replace injured tissues; however, the cells more frequently produce improvements by expressing therapeutic factors, such as the anti-apoptotic protein stanniocalcin-1 (STC-1). Previous reports indicated that subretinal administration of MSCs delayed photoreceptor degeneration in vivo. We tested the hypothesis that intravitreal injection of MSCs or STC-1 may delay retinal degeneration by decreasing apoptosis.
In preliminary experiments, cultures of retinal pigment epithelial cells (ARPE-19) were injured with hydrogen peroxide and treated with MSCs or STC-1. Viability was detected using MTT, and apoptosis was detected by measuring caspase activity and annexin V/PI uptake. Also, we administered STC-1 or MSCs via intravitreal injection in two models of retinal degeneration: the Royal College of Surgeons (RCS) rat and the S334ter-3 rhodopsin transgenic rat. Photoreceptor rescue was assessed by measurement of outer nuclear layer (ONL) thickness and quantitative gene expression assays for markers of photoreceptors and apoptosis.
The in vitro studies demonstrated that MSCs and STC-1 reduced apoptosis of ARPE-19. In the RCS rat model, injection of MSCs or STC-1 blunted the decrease in photoreceptor gene expression and reduced markers of apoptosis. In the S334ter-3 rats, injections of STC-1 reduced the decline in ONL thickness.
STC-1 was effective in decreasing apoptosis induced by oxidative damage to ARPE-19. In addition, intravitreal administration of STC-1 rescued photoreceptors in two different rodent models of retinal degeneration, apparently by decreasing apoptosis. The results raise the possibility that intravitreal administration of either MSCs or STC-1 may be an effective and less invasive therapy for retinal degeneration than subretinal injection of MSCs or other stem/progenitor cells.
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