title: Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model.
abstract: Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation.
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: H Y Lopilly
authors.initials: HY
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: C K
authors.initials: CK
authors.lastname: Park
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D016923:Cell Death; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology*; D007429:Intraocular Pressure; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000225:Adenine; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C025946:3-methyladenine