Autophagy-induced regression of hyaloid vessels in early ocular development.
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 fails, 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.
Kim
Jeong Hun
JH
Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University College of Medicine & Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Korea.
Kim
Jin Hyoung
JH
Yu
Young Suk
YS
Mun
Ji Young
JY
Kim
Kyu-Won
KW
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000033:anatomy & histology / Q000254:growth & development; D012171:Retinal Vessels / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D053148:Caspase 3; D020123:Sirolimus