Blood Vessel Maturation by Disintegrin in Oxygen-Induced Retinopathy

Abstract

RGD-containing disintegrin EGT022 stimulated vascular maturation in OIR mouse model. Experimental results suggest that EGT022 is useful for treatments to improve ischemia in nonproliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy.

A nonrandomized phase 2 trial of EG-Mirotin, a novel, first-in-class, subcutaneously delivered peptide drug for non-proliferative diabetic retinopathy

“…EG-Mirotin is a drug containing an RGD sequence (Coller, BS et al ., 1995) and our in-house experimental data provide novel observations: (i) EGT022, containing an RGD sequence, restores retinal blood vessels in OIR mouse model (data not shown), (ii) the EGT022-induced maturation of functional retinal blood vessels is closely associated with pericyte recruitment and blood vessel integrity (Jang, JW et al ., 2015). Interestingly, it is assumed that the statistically significant ameliorating effect on ischemia and leakage can be attributed to the active ingredient and molecular mode of action of EG-Mirotin by aforementioned recruiting pericytes (Papetti, M et al ., 2002) and then stabilizing blood vessels…”

“…Efficacy of EG-Mirotin in retinal edema has been demonstrated in the Miles assay model as a supplemental assay to assess the vascular permeability of the microvessels. EG-Mirotin appeared to be effective to ameliorate retinopathy-related abnormalities for up to 3 weeks as demonstrated by OCT, fundoscopy, angiography and histopathology in the streptozotocin (STZ) induced model of diabetic retinopathy in rats (Jang, JW et al . 2016)…”

“…EGT022 is a protein containing an arginine-glycine-aspartic acid sequence [18], and our in-house experiments provided novel data: (i) EGT022 restores retinal blood vessels in the OIR mouse model (data not shown) and (ii) EGT022-induced maturation of functional retinal blood vessels is closely associated with pericyte recruitment and blood vessel integrity [8]. It can be assumed that the significant reduction in ischemia and leakage can be attributed to the active ingredient of EG-Mirotin and its molecular mode of action of pericyte recruitment [19], thereby stabilizing blood vessels.…”

“…Microvessels are composed of tubules that form vascular endothelial cells and pericytes that support and surround them (Bergers, G et al , 2005; Zhao H et al ., 2019). Pericytes are vascular cells that contribute to stabilization capillary beds and their correct interaction with the extracellular matrix (ECM) is very important for microvascular development (Jang, JW et al ., 2016).…”

“…Microvessels are formed by vascular endothelial cells and pericytes that support and surround them [6,7]. Pericytes contribute to the stabilization of capillary beds, and their correct interaction with the extracellular matrix is essential for microvascular development [8]. If diabetes-induced changes worsen, pericyte loss and basement membrane thickening will eventually lead to loss of microvessels, i.e., NPDR [9].…”