Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against glaucomatous damage

Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB...

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Bibliographic Details
Published in:The American journal of pathology Vol. 179; no. 6; p. 2788
Main Authors: Wei, Xin, Yu, Zhanyang, Cho, Kin-Sang, Chen, Huihui, Malik, Muhammad Taimur A, Chen, Xiaoming, Lo, Eng H, Wang, Xiaoying, Chen, Dong F
Format: Journal Article
Language:English
Published: United States 01.12.2011
Subjects:
Animals
Cells, Cultured
Glaucoma - metabolism
Glaucoma - physiopathology
Globins - metabolism
Globins - physiology
Intraocular Pressure - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondrial Diseases - metabolism
Mitochondrial Diseases - physiopathology
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Oxidative Stress
Reactive Oxygen Species - metabolism
Retinal Ganglion Cells - physiology
Superoxides - metabolism
ISSN:1525-2191, 1525-2191
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Summary:Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Elevation of IOP stimulated a transient up-regulation of endogenous NGB in RGCs. Constitutive overexpression of NGB in transgenic mice prevented RGC damage induced by glutamate cytotoxicity in vitro and/or by chronic IOP elevation in vivo. Moreover, overexpression of NGB attenuated ocular hypertension-induced superoxide production and the associated decrease in ATP levels in mice, suggesting that NGB acts as an endogenous neuroprotectant to reduce oxidative stress and improve mitochondrial function, thereby promoting RGC survival. Thus, NGB may modulate RGC susceptibility to glaucomatous neural damage. Manipulating the expression and bioactivity of NGB may represent a novel therapeutic strategy for glaucoma.
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ISSN:1525-2191
1525-2191
DOI:10.1016/j.ajpath.2011.08.015