Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Proteomics investigations reveal molecular similarities and differences between human and rat retinas under glaucoma conditions. (#125)

Mehdi Mirzaei 1 2 3 , Vivek Gupta 1 , Joel Chick 4 , Mark Molloy 2 3 , Paul Haynes 3 , Stuart Graham 1
  1. Faculty of Medicine and Health Sciences,, Macquarie University, Sydney, NSW, Australia
  2. Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia
  3. Molecular Sciences, Macquarie University, Sydney, NSW, Australia
  4. Department of Cell Biology, Harvard Medical School, Boston, MA, United States

Glaucoma is a progressive neurodegenerative disease of the eye that represents one of the major causes of irreversible blindness worldwide. This complex degenerative disorder is characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. While several risk factors have been identified that are associated with premature loss of RGCs, high intraocular pressure is currently the most significant risk factor in glaucoma. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies however remain ill-defined. Greater understanding of the underlying neurodegenerative processes is crucial for the development of effective therapeutic strategies for glaucoma.

In this study, we sought 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. Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour tissues collected from glaucoma patients and age-matched controls (n: 20). Rat model of glaucoma was generated in the lab using repetitive microbead injections into the anterior chamber of the eye to help increase the intraocular pressure and retinal tissues analysed using TMT proteomics analysis (n: 10). This was followed by comprehensive functional pathway and protein network interaction analysis. 

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 and cholesterol metabolism in human glaucoma retinas suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation, protein misfolding and glutathione biosynthesis pathways were identified in both the human and animal glaucoma model.