Aqueous humor protein dysregulation in primary angle-closure glaucoma

Original Paper

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.

Keywords

Glaucoma Aqueous humor Proteomics Primary angle-closure glaucoma ApoE 

Notes

Acknowledgements

This work is in part supported by grants from the Singapore Ministry of Education (MOE2014-T2-2-043 and MOE2016-T2-2-018), the National Medical Research Council of Singapore (NMRC-OF-IRG-0003-2016), and National Healthcare Group Small Innovative Grant (Grant # 13018).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study was in agreement with the Declaration of Helsinki and approved by the Institutional Review Board at the Tan Tock Seng Hospital (TTSH). Informed consent was obtained from each patient.

Supplementary material

10792_2018_885_MOESM1_ESM.xlsx (724 kb)
Supplementary material 1 (XLSX 723 kb)
10792_2018_885_MOESM2_ESM.xlsx (440 kb)
Supplementary material 2 (XLSX 440 kb)
10792_2018_885_MOESM3_ESM.docx (148 kb)
Supplementary material 3 (DOCX 148 kb)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Sunil S. Adav
    • 1
  • Jin Wei
    • 1
    • 2
  • Jingru Qian
    • 1
  • Nicola Yi’An Gan
    • 3
  • Leonard W. L. Yip
    • 3
  • Siu Kwan Sze
    • 1
  1. 1.School of Biological SciencesNanyang Technological UniversitySingaporeSingapore
  2. 2.Eye CenterRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  3. 3.Department of Ophthalmology, National Healthcare Group Eye InstituteTan Tock Seng HospitalSingaporeSingapore

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