The crosstalk between VEGF signaling pathway and long non-coding RNAs in neovascular retinal diseases: Implications for anti-VEGF therapy

Angiogenic ocular conditions are known as the major cause of vision loss including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. Recent evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, plays an important role in angiogenesis of these pathogenic conditions making this functional protein as a significant therapeutic target. Current therapies, such as anti-VEGF drugs, laser photocoagulation, and vitrectomy surgery raise concerns due to limited efficacy, retinal and vasculature damages, and the unresponsiveness of patients to the treatments. Therefore, more detailed investigations regarding the pathogenesis of ocular diseases and also search for novel therapeutic targets for reversing the ocular neovascularization are necessary. Several investigations have indicated a critical role of non coding RNAs, particularly long non-coding RNAs (lncRNAs) in the pathogenesis and regulation of the ocular neovascularization. Moreover, non-coding RNAs might be good molecular targets for intervention of neovascular eye diseases. Therefore, this review summarizes the current understanding of signaling mechanisms of VEGF pathway. We will further review the interactions between VEGF signaling and lncRNAs, and the impact of lncRNAs on VEGF signaling. Finally, the potential treatment strategies of lncRNAs in neovascular eye diseases will be discussed.