Over-expression of CNTF in bone marrow mesenchymal stem cells protects RPE cells from short-wavelength, blue-light injury

Wen Lin, Guoxing Xu

Increasing evidence has demonstrated that excessive blue-light (BL) with high photochemical energy and phototoxicity could induce apoptosis in retinal pigment epithelium (RPE) cells. RPE apoptosis leads to retina damage and further aggravate age-related macular degeneration (ARMD). Because of their neuroprotective, plasticity, and immunomodulatory ability, bone marrow mesenchymal stem cells (BMSCs) are recognized for retinal neuroprotection. RPE cells possess ciliary neurotrophic factor (CNTF) receptor complexes and can respond to CNTF; hence, we investigated the effects of BMSCs over-expressing CNTF on BL-injured RPE cells. BL-injured RPE cells were co-cultured with CNTF-BMSCs and GFP-BMSCs for 24 and 48 h. Superoxide dismutase and malondialdehyde assays were conducted to examine the effects of CNTF-BMSCs on the oxidative stress of RPE cells. VEGF protein secretion by RPE was determined by ELISA, and western blotting analysis was used to determine apoptotic protein expression and autophagic flux. Immunofluorescence was used to demonstrate the relationship between autophagy and apoptosis. We found that CNTF-BMSCs enhanced antioxidant capacity, decreased VEGF secretion, promoted autophagic flux, and inhibited apoptosis in BL-injured RPE cells, compared to GFP-BMSCs. Our findings suggest that CNTF over-expression enhances the protective effects of BMSCs on RPE cells, thus indicating subretinal-transplantation of CNTF-BMSCs may be a promising therapy for BL-injured retina.