期刊
TRENDS IN MOLECULAR MEDICINE
卷 19, 期 10, 页码 586-593出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2013.06.005
关键词
primary open angle glaucoma; ocular hypertension; myocilin; neurodegenerative disease
资金
- NEI NIH HHS [R01 EY015873] Funding Source: Medline
- NIEHS NIH HHS [RC1 ES018255] Funding Source: Medline
Primary open angle glaucoma (POAG) is a common late-onset neurodegenerative disease. Ocular hypertension represents a major risk factor, but POAG etiology remains poorly understood. Some cases of early-onset congenital glaucoma and adult POAG are linked to mutations in myocilin, a secreted protein of poorly defined function. Transgenic overexpression of myocilin in Drosophila and experiments in mice and human populations implicate the unfolded protein response (UPR) in the pathogenesis of glaucoma. We postulate that compromised ability of the UPR to eliminate misfolded mutant or damaged proteins, including myocilin, causes endoplasmic reticulum stress, resulting in functional impairment of trabecular meshwork cells that regulate intraocular pressure. This mechanism of POAG is reminiscent of other age-dependent neurodegenerative diseases that involve accumulation of protein aggregates.
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