Potential therapeutic effects of pigment epithelium-derived factor for treatment of diabetic retinopathy

Abstract

Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.

Keywords: diabetic retinopathy; molecular therapeutics; pigment epithelium derived factor; pleiotropic functions.

Figure 1. The summary of PEDF targets multiple pathways exerting pleiotropic functions in the pathology of diabetic retinopathy

VEGF: Vascular endothelial growth factor; PEDF: Pigment epithelium derived factor; HIF-1: Hypoxia-inducible factor-1; AGEs: Advanced glycation end products; RAGE: AGE receptor; ICAM: Intercellular adhesion molecular; TNF-α: Tumor necrosis factor-α; MCP-1: Monocyte chemoattractant protein-1; ROS: Reactive oxygen species; NF-κB: Nuclear transcription factor-κB; NMDA receptor, N-metil-D-aspartame receptors; GS: Glutamine synthetase; MAPK: Mitogen-activated protein kinase; GSK: Glycogen synthase kinase; Ang II: Angiotensin II.