Purpose : Glaucoma is a progressive neurodegenerative disease of the eye characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies, however, remain ill-defined. This study was aimed to investigate the molecular basis of glaucoma pathogenesis by taking a systems-level perspective of the human retinal proteome and compare it with experimental glaucoma animal model using unbiased quantitative proteomics approaches. Methods : Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour collected from glaucoma patients and age-matched controls (average ages: control 64.5 ± 10, n = 10 and glaucoma: 71.5 ± 8.5, n = 10, respectively). A rat model of glaucoma was generated using weekly microbead injections into the anterior chamber of the eye to help increase the intraocular pressure (n: 10). The differentially expressed proteins identified based on a two-sample t-test (p < 0.05) and a fold change threshold (≥1.3 for up-regulation or ≤0.76 for down-regulation). Finally, selected markers were validated using western blotting and electrochemiluminescence assay. Results : About 5000 proteins were quantified from both the human and experimental glaucoma model. Pathway analyses of differentially regulated proteins indicated specific activation of classical complement pathway (up-regulation of C1q, C1s, C1r, C4a, C4b, C3, C5, C6, C7, C8a, C8b, C8g and C9 proteins) and cholesterol metabolism (up-regulation of APOA1, APOA4, APOC1, APOC3, APOH, APOB, APOE, APOL1, APOM, APOA2, APOL2 and APOC2 proteins) in human glaucoma retinas specifically suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation (down-regulation of electron transport chain complex proteins), protein folding (down-regulation of crystalline proteins) and glutathione biosynthesis pathways (up-regulation of GSTs), were identified in both human and animal glaucoma model.
|Number of pages||1|
|Journal||Investigative Ophthalmology and Visual Science|
|Publication status||Published - 2018|
|Event||Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2018 - Honolulu, United States|
Duration: 29 Apr 2018 → 3 May 2018