Abstract
Purpose :
Retinopathy of Prematurity (ROP) is a proliferative retinal microvascular disorder which is one of the leading causes of childhood blindness. Development of retinal vasculature is incomplete before 30 weeks of gestation. Supplemental oxygen provided to premature infants in the neonatal intensive care unit (NICU) further delays peripheral retinal vascular development. As a result, when infants are returned to room oxygen concentrations, the avascular peripheral retina is hypoxic and instigates abnormal neovascularization. Decorin (Dcn) is a small leucine rich proteoglycan that is an integral extracellular matrix (ECM) structural protein. Dcn can elicit diverse molecular signals to modulate cell permeability, migration, and angiogenesis. Since retinal vasculature depend on an optimal microenvironment in the complex ECM to develop, we hypothesize that Dcn may play a significant role in modulating the retinal vascular microenvironment during development and thus play a role in ROP. This study aims to determine Dcn’s therapeutic potential for the management of ROP.
Methods :
Oxygen induced retinopathy (OIR) rat model of ROP was achieved by cycling infant Sprague Dawley rats between 50% and 10% oxygen every 24 h for 14 days. Recombinant human decorin (rhDcn) was injected intravitreally at postnatal day 14 (P14). Retinal tissues were collected at P14, P18 and P21. Retinal flat mounts were stained with isolectin-IB4 to evaluate retinal vasculature. Quantitative real-time PCR, immunohistochemistry and western blots were performed to determine gene and protein expression of angiogenic markers.
Results :
Dcn expression in OIR rats was reduced. Intravitreal injection of rhDcn at P14 encouraged physiological growth of retinal vessels and prevented abnormal neovascularization seen in P18 and P21 OIR rats. Treatment with rhDcn also reduced HIF-1a and VEGF expression in OIR rats.
Conclusions :
Dcn treatment to OIR rats at P14 reduces the expression of angiogenic markers and prevents abnormal neovascularization seen in OIR rats. Dcn regulates the retinal vascular microenvironment and may potentially be a novel therapeutic strategy for the management of ROP.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.