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X. Wei, Z. Yu, K. Cho, H. Chen, I.-H. Pang, X. Chen, X. Wang, D. Chen; Neuroglobin: Endogenous Neuroprotectant for Retinal Ganglion Cells Against Glaucomatous Damage. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3191.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of Neuroglobin (Ngb) in retina ganglion cells (RGCs) survival following elevation of intraocular pressure (IOP) in mice and to elucidate the underlying mechanisms of Ngb function.
The elevation of IOP was induced in adult C57BL/6J wild-type and Ngb transgenic (TG) mice by anterior chamber injection of fluorescent polystyrene microbeads (10 um). The control group received injection of phosphate buffered saline (PBS) into the anterior chamber. Mouse IOP was measured every four days using a Tonolab, and the animals were sacrificed at day 0, 3, 28 and 56 post-injection. The pattern of Ngb expression in the retina was detected using real-time PCR, Western Blot and immunohistochemistry. RGC loss was assessed quantitatively at 8 weeks after anterior chamber injection of microbeads. Moreover, the role of Ngb on RGC survival was also examined in culture. The levels of superoxide and ATP in retina were compared in wild-type and Ngb TG mice before and after the elevation of IOP.
Injection of polystyrene microbeads to adult C57BL/6J and Ngb TG mice consistently induced elevation of IOP, similar to our previous report. Up-regulation of Ngb expression was observed in RGCs of wild-type mice at as early as 3 days after elevation of IOP. Overexpression of Ngb in TG mice significantly improved RGCs survival after IOP elevation. In culture, RGCs derived from Ngb TG mice exhibited increased protection against glutamate neurotoxicity. Moreover, we noted that elevated IOP induced less superoxide products but increased ATP levels in the ganglion cell layer of Ngb overexpressing mice as compared to that in wild-type mice.
Our data suggest that Ngb is a neuroprotective molecule in RGCs in this glaucoma model, and it may increase RGC survival by decreasing oxidative stress and improving mitochondria function.
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