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Hu xinxin, Yi Dai, Xing-Huai Sun; Overexpression of Parkin Protects Retinal Ganglion Cells in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2617. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of parkin in regulating mitophagy, and whether overexpression of parkin can protect retinal ganglion cell (RGC) in ocular hypertensive rats.
Chronic intraocular pressure (IOP) elevation was induced by translimbal laser photocoagulation of the trabecular meshwork in Sprague-Dawley rats. Morphological analysis on mitochondria and autophagosomes in optic nerve were performed by electron microscope tomography. Survival of FluoroGold-labeled retinal ganglion cells (RGCs) was assessed 2 weeks later. Eyeballs and cultured RGCs were transfected with parkin using viral vectors. Proteins expressions of parkin, optineurin, GFAP, OPA1, LC3-I and-II, and LAMP1 were analyzed by immunohistochemistry and western blot.
The protein level of parkin and 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 increased RGC survival, promoted optineurin expression, and improved mitochondrial health. While 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 IOP elevation.
Overexpression of parkin exerted a significant protective effect on RGCs and partially restored dysfunction of mitophagy in response to cumulative IOP elevation. Interventions to modulate the parkin-mediated mitochondria pathway may be useful in protecting RGCs in glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Fig 1. Retinal ganglion cell (RGC) survival in the hypertensive rat retina after overexpression of parkin.
Fig 2. Effect of parkin overexpression on hypertensive retina. Western blot analysis of parkin, GFAP, OPA1, and optineurin proteins in parkin transfected retina.
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