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Ahmed Gomaa, Alexandra Vayl, Gangaraju Rajashekhar; CD146+ Adipose stromal cells localize and improve the retinal function in I/R injury. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4006.
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© ARVO (1962-2015); The Authors (2016-present)
We have demonstrated previously that intravitreal injection of adipose stromal cells (ASC) in the eyes of diabetic rats improved the retinal function. Well defined ASC population with highest safety and efficacy are needed to plan for future human clinical trials. Recently, CD146+ population of vascular pericytes have been recognized as potential utility in particular therapeutic areas. In this study, we aim to identify if CD146+ population of pericyte ASC have better ability to improve the retinal function in I/R model of retinopathy.
Unilateral retinal I/R were done in adult Lewis rats by transiently elevating the intraocular pressure for 1h. Uninjured eyes served as I/R controls. After day 7 of reperfusion the animals were randomized to receive intravitreal CD146+ ASC, CD146- ASC, (10,000 cells) or saline injections. After further 6-7 days, retinal function was assessed by Electroretinogram (ERG), retinal structure and thickness was assessed by optical coherence tomography (OCT) and retinal whole mounts and confocal microscopy for ASC localization to retinal vasculature.
Retinal I/R resulted in a significant reduction in “b” wave amplitude (as measured by ERG) compared to anesthetized live un-injured control rats. Retinal I/R induced reduction in ‘b’ wave was significantly improved by CD146+ ASC compared with CD146- ASC at day-6 post injection (165.3 ± 24 v/s 211.5 ± 35 µvolts < 0.0343; N=6). In addition, at day 7 retinal I/R resulted in a significant reduction in total retinal thickness which was rescued with CD146+ ASC in I/R rats as assessed by OCT. Finally, confocal microscopy performed on retinal whole mounts from injured eyes that received CD146+ ASC demonstrated a significant localization and homing to the retinal vasculature in comparison to CD146- ASC cells.
Our findings suggest that CD146+ 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 CD146+ ASC, our data suggests that CD146+ ASC have the highest ability to home and integrate into retinal vasculature, perhaps as perivascular pericytes to repair damaged retinal vasculature.
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