Expression profile and regulation of telomerase reverse transcriptase on oxygen-induced retinal neovascularization

Purpose: Telomerase is critical for the control of replicative capacity, which plays a major role in proliferative retinal neovascularization. In this study, we investigated the expression profiles of telomerase reverse transcriptase (Tert) in a mouse model of oxygen-induced retinal neovascularization and explored the possibility of inhibiting a retinal Tert expression with small interfering RNAs (SiRNA) as a novel potential approach to suppress proliferative retinopathy. Methods: The mouse oxygen-induced retinal neovascularization model was used to examine expression profiles in different developmental phases and to assess the anti-angiogenic activity of Tert-SiRNA. Recombinant SiRNA plasmids were injected intravitreously into mice with or without pathological retinal neovascularization. Fluorescein angiography, vessel counting, and the expression levels of Tert mRNA and protein were used to evaluate the anti-angiogenic effects. Results: Retinal Tert expression, as assessed by both mRNA and protein levels, was significantly up-regulated during the proliferative phase of oxygen-induced retinal neovascularization. Intravitreous injection of Tert-SiRNA effectively suppressed the expression of Tert mRNA and proteins and inhibited retinal neovascularization, as confirmed by retinal flat angiography and vessel counting. Conclusions: The expression of Tert was up-regulated during the development of oxygen-induced retinal neovascularization. Inhibiting Tert expression with SiRNA is effective in suppressing retinal neovascularization, suggesting that telomerase may be a potential therapeutic target for treating proliferative retinopathy.