Autophagy-induced regression of hyaloid vessels in early ocular development

Abstract

The hyaloid vessel is a transient intraocular circulatory system that undergoes a complete regression as the retina becomes matured with retinal vascularization. If the complete involution of the hyaloid vessels failes, the pathological persistence of these vessels results in persistent hyperplastic primary vitreous (PHPV) associated with severe ocular pathologies. Unfortunately despite its clinical significance, cellular and molecular processes involved in hyaloid regression remain to be elucidated. Herein, we for the first time demonstrated that autophagy could contribute to the regression of hyaloid vessels in early developing retina. In developing retina, hyaloid vessel regression coincided with retinal vascular development; this occurred simultaneous with apoptotic and autophagic processes. Moreover, in vascular endothelial cells under hypoxic conditions, LC3-II conversion was detected along with caspase-3 activation. The autophagy inducer rapamycin induced autophagy-mediated cell death of vascular endothelial cells in a dose-dependent manner. Moreover, rapamycin significantly enhanced the involution of hyaloid vessels in the early developing eye. Therefore, our results suggest that the autophagy pathway would be involved in hyaloid regression that occurs during early ocular development. Furthermore, activation of the autophagy pathway could be considered for a therapeutic approach to PHPV.