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Ramesh Periasamy, Damian Kaminski, Rajashekhar Gangaraju; Critical role of CD140b in adipose derived stem cells in the rescue of retinal ischemia.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4540.
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© ARVO (1962-2015); The Authors (2016-present)
Ischemia-induced retinopathy is characterized by both degeneration of microvessels and neurons often leading to blindness. We have demonstrated previously that intravitreal injection of adipose derived stromal cells (ASC) in the eyes of diabetic and ischemia-reperfusion (I/R) injury rats improved the retinal function. In this study we hypothesized that CD140b [Platelet derived growth factor (PDGF) receptor] in ASC is essential for this function.
Unilateral retinal I/R were done in adult Lewis rats by transiently elevating the IOP for 1h. On day 7 of reperfusion, the animals were randomized to receive intravitreal CD140b+ASC, CD140b-ASC (1,000 cells/eye) or saline injections. On day 14, retinal function assessed by ERG; apoptosis and gliosis were assessed by histology, and retinal flat mounts after 21 days for ASC localization by confocal microscopy. In vitro, CD140b was knockdown by siRNA. Proliferation, adhesion and migration of CD140bKD ASC were assessed.
Retinal I/R resulted in a significant reduction in “b” wave amplitude were significantly improved by CD140b+ ASC compared with CD140b- ASC (90.6 ± 37.1 vs 20.3 ± 8.9 SEM, p<0.05 at 25Cd.s.m2). Interestingly, Confocal microscopy performed on retinal flat mounts from injured eyes that received CD140b+ ASC demonstrated increased localization and homing to the retinal vasculature in comparison to CD140b- ASC. Histology confirmed decreased apoptosis (73.1 ± 12.2 vs 140.9 ± 11.8 SEM, p<0.0001) and gliosis (66.5 ± 6.1 vs 128.2 ± 24.3 SEM, p=0.0006) with CD140b+ASC compared with CD140b-ASC. In vitro CD140b knockdown in ASC resulted in decreased adhesion to Laminin compared to the siRNA control (27.6 ± 5.2 vs 37.2 ± 5.1 SD, p=0.04). Similarly, the proliferation of ASC reduced when CD140b was knockdown (135.0 ± 11.7 vs 43.2 ± 19.1 SD, p=0.002). Finally, CD140b knockdown in ASC also demonstrated significant reduction in the ability to migrate compared to control at 24-h post injury in the presence of PDGF-bb (79.9 ± 4.4 vs 89.9 ± 1.1 SD, p<0.02).
Our results support the hypothesis that CD140b play a vital role in ASC to improve the retinal regeneration. Although more studies warranted, enrichment of pericytic CD140b+ASC would be highly effective at being incorporated into the retinal perivasculature that is damaged in ischemic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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