title: Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model.
abstract: Primary open angle glaucoma (POAG) is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs). In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi) and late or degraded autophagic vacuoles (AVd) accumulated in the ganglion cell layer (GCL) and in the inner plexiform layer (IPL) as determined by transmission electron microscopy (TEM) analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1) and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Shuifeng
authors.initials: S
authors.lastname: Deng
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Yan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tian
authors.forename: Hongrui
authors.initials: H
authors.lastname: Chen
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Yang
authors.forename: Yehong
authors.initials: Y
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure; D008247:Lysosomes / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009798:Ocular Hypertension / Q000150:complications*; D012165:Retinal Ganglion Cells / Q000473:pathology*