Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy

Abstract

Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.

Recovery of Corneal Sensitivity and Increase in Nerve Density and Wound Healing in Diabetic Mice After PEDF Plus DHA Treatment

“…Oxidative stress has been proposed as a primary pathogenic factor responsible for the development and progression of diabetic peripheral neuropathy in which mitochondrial dysfunction, induced by chronic hyperglycemia, leads to axonal regenerative failure (30–32). In the eye, PEDF-mediated mechanisms have been reported to protect the retina against reactive oxygen species damage in diabetic retinopathy and neuropathy (33,34). PEDF attenuates caspase-3 activity by improving the ratio of Bcl2/Bax in advanced glycation end product–exposed pericytes and reduces reactive oxygen species generation by downregulating the membrane components of NAPDH oxidase, p22 PHOX , and gp91 PHOX , thus suppressing NADPH oxidase activity in advanced glycation end product–exposed endothelial cells (35,36).…”

Effect of shRNA-mediated knockdown of vascular endothelial growth factor on the proliferation of choroid-retinal endothelial cells under hypoxic conditions

“…Secondly, VEGF may induce vascular endothelial cells to increase their vascular permeability, causing vasoconstriction factors, clotting factors, plasma proteins and fibrins to extravasate into the extracellular space. Exosmic fibrins and other proteins, such as fibronectin, are condensed into a fibronectin gel, which provides a matrix component for endothelial cells and other cells, facilitating migration and intrusion, and ultimately converting the cells into vascularized connective tissue (17). In addition, VEGF is a selective mitogen of endothelial cells that is able to stimulate the growth of new blood vessels.…”

Biomarkers in Diabetic Retinopathy

“…PEDF is excreted in the urine; circulating levels rise with renal disease. PEDF has potent antiangiogenic properties as well as anti-inflammatory and anti-oxidant effects [3,[236][237][238]. It is detectable at high levels in blood.…”