Endothelin-1 Mediated Regulation of Extracellular Matrix Collagens in Rat Optic Nerve Head

Abstract

Purpose: : Endothelin -1 (ET-1) has been implicated in glaucoma pathology. extensive extra cellular matrix (ECM) remodeling with increase in collagen type I and type VI at the levels of optic nerve head is observed in POAG subjects and in animal models of glaucoma. The purpose of this study was to determine the effects of ET-1 on the regulation of ECM in rat optic nerve head.

Methods: : Adult Wistar- Kyoto rats were injected with ET-1 intra - vitreally. In order to determine the role of ET_A and ET_B receptors in ET-1 mediated collagen regulation, ET_B deficient transgenic adult Wistar-Kyoto rats were used in the study. ET-1 mediated changes in collagen type I and type VI expression was determined by immunohistochemistry.

Results: : Immunohistochemical analysis of optic nerve head sections revealed an increase in collagen type I and type VI deposition following intravitreal injection of ET-1. ET-1 mediated collagen VI deposition was less in ET_B deficient transgenic rats indicating the involvement of ET_B receptors in the regulation of collagen VI synthesis.

Conclusions: : These results suggest that ET-1 regulates extracellular matrix collagen synthesis in rat optic nerve head and contributes to ECM remodeling.

Keywords: extracellular matrix • receptors • receptors: pharmacology/physiology