Role of novel GPCR receptors in retina homeostasis and disease

Supervisor: Dr. Jean Yves Springael and Dr. François Willermain

In order to preserve vision, a precise control of immune response in the retina is required. This homeostasis is broken during intra-ocular inflammatory diseases (uveitis), retinal degeneration and vasculopathy such as diabetic retinopathy and age related macular degeneration. In non-infectious autoimmune uveitis, retinal specific autoreactive lymphocytes invade the retina starting an inflammatory response implicating both resident and recruited immunocompetent cells (1). It is one of the leading causes of blindness in the developed countries. Current pharmacological treatments for uveitis often have various side effects, and there is still a need for new therapeutic approaches (2). G protein coupled receptors (GPCR) constitute the most important targets for human therapeutics. The proposed PhD project aims to investigate the role of novel GPCR receptors in the development of uveitis by using mice invalidated for the expression of these receptors, and a model of experimental auto-immune uveitis (EAU) which is widely used to delineate the pathophysiological processes of ocular autoimmunity and develop therapeutic approaches (3). Importantly, as retinal inflammation is central to other frequent retinal pathology, new development made in uveitis therapy might be translate in other blinding conditions. This program will involve an interdisciplinary knowledge across molecular and cellular biology, transcriptomics, animal handling, tissue processing and immunohistological methods. 

References:

1. Perez and Caspi, Immune mechanisms in inflammation and degenerative eye diseases. Trends Immunol. (2015) 36(6)354

2. Shome et al., Blocking inflammasome: a novel approach to treat uveitis Drug discovery today (2021) 26, 2839

3. Lipski et al., MHC class II expression and potential antigen-presenting cells in the retina during experimental autoimmune uveitis  J. Neuroinflammation (2017) 14(1):136

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