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Title: Aqueous humor protein dysregulation in primary angle-closure glaucoma
Authors: Adav, Sunil Shankar
Wei, Jin
Qian, Jingru
Gan, Nicola Yi'An
Yip, Leonard W. L.
Sze, Siu Kwan
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Adav, S. S., Wei, J., Qian, J., Gan, N. Y., Yip, L. W. L. & Sze, S. K. (2019). Aqueous humor protein dysregulation in primary angle-closure glaucoma. International Ophthalmology, 39(4), 861-871.
Project: MOE2014-T2-2-043
Grant #13018
Journal: International Ophthalmology
Abstract: Purpose: Primary angle-closure glaucoma (PACG) is associated with increased intraocular pressure, optic nerve damage, and progressive vision loss, but the molecular mechanism that underpins retinal ganglion neuropathy in PACG remains poorly understood. To better understand the pathogenesis of human PACG, we performed the first comprehensive proteomic analysis of aqueous humor (AH) samples from PACG patients and matched control donors to study pathogenic alteration in AH composition in disease. Methods: High-resolution, label-free, liquid chromatography–tandem mass spectrometry-based quantitative proteomic analyses were performed in AH samples collected from PACG patients and a matched control cohort of patients with cataracts. Results: The AH proteome comprised of 1363 distinct proteins, of which more than 50% were differentially expressed in PACG (773 total; 501 up-regulated, 272 down-regulated). AH from PACG patients was enriched in atypical collagens and fibronectins, suggesting that the composition of the trabecular matrix is significantly altered in disease. Pathway and cluster analyses revealed that AH protein modulation in PACG is closely associated with biological processes including platelet degranulation, cellular import/export mechanisms, and control of protease activity. In addition, critical mediators of oxygen homeostasis and neuronal function in AH were significantly dysregulated in disease, strongly implicating oxidative stress responses in PACG-associated nerve damage. Conclusions: Altered AH proteome in human PACG indicated oxidative stress in the neuronal damage that preceded vision loss. Identifying key mediators of PACG pathology will yield new prognostic biomarkers and novel targets for future therapeutic interventions.
ISSN: 0165-5701
DOI: 10.1007/s10792-018-0885-3
Rights: © 2018 Springer Science+Business Media B.V., part of Springer Nature. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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