Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Can retina as part of the CNS unfold the common pathophysiology underlying the neurodegenerative diseases? (#725)

Mehdi Mirzaei 1 2 , Liting Deng 2 , Kanishka Pushpitha 3 , Yunqi Wu 1 2 , Dana Pascovici 1 2 , Jemma Wu 1 2 , Matthew J McKay 1 2 , Paul A Haynes 2 , stuart L Graham 3 , Vivek Gupta 3
  1. Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia
  2. Molecular Science , Macquarie University, Sydney, NSW, Australia
  3. Clinical Medicine , Macquarie University, Sydney, NSW, Australia

The concept of “the eye as a window to the brain” is increasingly being explored to examine brain function in areas of health and disease. During embryonic development, the retina and optic nerve project from the brain, and are thus considered part of the central nervous system (CNS). Retinal tissue demonstrates similarities with the brain in terms of neural anatomy and cellular and biochemical responses to injury. In fact, similar to the blood-brain barrier, retinal tissue maintains a distinct immune environment that is facilitated by the blood-retinal barrier.

Retina is increasingly being investigated to assess the effects of brain related pathological conditions such as Alzheimer’s disease (AD). These molecular changes are reported to exhibit pathological similarities with retinal neurodegenerative disorders including glaucoma.  AD is now understood to be associated with glaucoma with higher rates of incidence of glaucoma being reported in some cohorts of Alzheimer’s patients.  The exact molecular basis of this association remains poorly defined.

The study aims to decipher the common molecular mechanisms underlying retinal pathology in response to various neurodegenerative disorders affecting the retina, particularly in glaucoma and AD. To achieve this, we employed quantitative proteomics and biochemical approaches coupled with bioinformatics tools to analyse retinal glaucoma tissue from human post-mortem subjects and an animal model of experimental glaucoma. The findings were correlated with data obtained from retinal and brain tissues from APP/PS1 double transgenic mutant mouse model of AD. Our results reveal several novel candidate markers and biochemical pathways that were commonly affected in the two diseases. Hallmark proteins of AD such as amyloid beta and tau were identified to be modulated in these two distinct neural tissues of the CNS. This study provides mechanistic insights into the common pathophysiology underlying neurodegenerative diseases in the retina and brain.