Decorin may Restore Endothelial Cell Integrity in the Retina

Abstract

Purpose : The inner blood-retinal barrier (iBRB) mainly comprises of retinal microvascular endothelial cells (RMECs) regulating the transport of molecules such as ions, proteins and water required for the maintenance of retinal homeostasis. Small leucine rich proteoglycans, such as decorin, constitute an integral component of the endothelial cell extracellular matrix (ECM). Since decorin can elicit diverse molecular signals to modulate cell permeability, migration, and survival of RMECs, the present study aims to study the role of decorin in restoring hypoxia-induced damage to the endothelial cell integrity in the retina.

Methods : Human retinal microvascular endothelial cells (HRMECs) were cultured to confluency and subjected to hypoxia +/- 200 nM human recombinant decorin for 24 h. Cells were analysed in real time using xCELLigence system for 7 days. iBRB was evaluated using FITC-dextran permeability and tight junction proteins, including ZO1 by immunohistochemistry and western blotting. Cellular proliferation and scratch wound migration assays were also performed. Cell media was collected to measure the decorin levels using ELISA.

Results : Biochemical and immunoassays characterized the localization and release of decorin by HRMECs. Furthermore, decorin treatment to HRMECs exposed to hypoxia effectively reduced cell permeability and restored tight junction function. Additionally, decorin prevented aberrant endothelial cell proliferation and migration.

Conclusions : Decorin may counteract the hypoxia-induced iBRB disruption in the retinal microvascular endothelial cells, thereby presenting new therapeutic strategies for the management of retinal vascular disorders.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.