Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: retina • retinal degenerations: cell biology • neuroprotection