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Growing evidences have linked impaired mitophagy with neurodegenerative diseases, while the E3 ubiquitin ligase parkin may play a key role. However, the pathophysiological relationship between parkin and glaucoma remains largely unknown. Using chronic hypertensive glaucoma rats induced by translimbal laser photocoagulation, we show here that the protein level of parkin and its downstream optineurin proteins were increased in hypertensive retinas. The ratio of LC3-II to LC3-I, the number of mitophagosomes, and unhealthy mitochondria were increased in hypertensive optic nerves. Overexpression of parkin by viral vectors increased RGC survival in glaucomatous rats in vivo and under excitotoxicity in vitro. It also promoted optineurin expression and improved mitochondrial health. In parkin-overexpressed glaucomatous rats, the ratio of LC3-II to LC3-I, LAMP1 level, and the number of mitophagosomes in optic nerve were decreased at 3 days, yet increased at 2 weeks following intraocular pressure (IOP) elevation. These findings demonstrate that dysfunction of mitophagy exist in RGCs of glaucomatous rats. Overexpression of parkin exerted a significant protective effect on RGCs and partially restored dysfunction of mitophagy in response to cumulative IOP elevation.<\/jats:p>","DOI":"10.1038\/s41419-017-0146-9","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T15:01:01Z","timestamp":1516806061000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Overexpression of parkin protects retinal ganglion cells in experimental glaucoma"],"prefix":"10.1038","volume":"9","author":[{"given":"Yi","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghuai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"146_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1097\/ICU.0b013e3280895aea","volume":"18","author":"N Gupta","year":"2007","unstructured":"Gupta, N. & Yucel, Y. H. Glaucoma as a neurodegenerative disease. Curr. Opin. Ophthalmol. 18, 110\u20134 (2007).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"146_CR2","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0079-6123(08)01124-2","volume":"173","author":"NN Osborne","year":"2008","unstructured":"Osborne, N. N. Pathogenesis of ganglion \u201ccell death\u201d in glaucoma and neuroprotection: focus on ganglion cell axonal mitochondria. Prog. Brain Res. 173, 339\u201352 (2008).","journal-title":"Prog. Brain Res."},{"key":"146_CR3","first-page":"254","volume":"10","author":"S Zhang","year":"2016","unstructured":"Zhang, S. et al. High pressure-induced mtdna alterations in retinal ganglion cells and subsequent apoptosis. Front. Cell Neurosci. 10, 254 (2016).","journal-title":"Front. Cell Neurosci"},{"key":"146_CR4","doi-asserted-by":"publisher","first-page":"4903","DOI":"10.1167\/iovs.07-1661","volume":"49","author":"WK Ju","year":"2008","unstructured":"Ju, W. K. et al. 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