Inflammation and Immunology in Retinal Diseases

Presentation

The retina, is considered “immune privileged”, meaning that innate and adaptive immune responses are dampened or suppressed, possibly because it is particularly vulnerable to immunopathogenic collateral damage, as it has very limited regenerative capacities, and the irreversible damage to the retina and vision puts the fitness of the individual at risk. Nevertheless, this immune privilege is relative and in diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), we observe the protracted accumulation of pathogenic mononuclear phagocytes (MPs), an over-activation of the innate immune system that is observed in diabetes and many age-related diseases. More dramatically, in non-infectious autoimmune uveitis (NIU), tissue damage is associated with the presence of autoreactive T-cells against retinal antigens, with secondary infiltration of pro-inflammatory MPs that are largely responsible for the tissue destruction that characterize this pathology. 

AMD and inflammation (Florian Sennlaub)

Recent evidence suggests an implication of inflammatory mediators in AMD. We have focused our interest on the role of microglial cells (MC) and mononuclear phagocyte (MP) in this condition. Our data indicates that:

• MC/MP accumulate in affected areas of the macula in human AMD
• MC/MP accumulate leads to/contributes to Drusen formation, retinal degeneration and exacerbated neovascularization, similarly to AMD. Our data suggests an important role of subretinal MC and MP accumulation in the development of AMD. Inhibiting subretinal inflammation in AMD is a promising avenue to develop new efficient therapies.

Diabetic retinopathy and inflammation (Xavier Guillonneau)

Diabetic Retinopathy (DR) affects more than 60% of people with type 2 diabetes. Non-proliferative DR (NPDR), the earliest stage of DR, is characterized by retinal inflammation and the progressive degeneration of retinal capillaries, breakdown of the blood-retinal barrier and extravasation of plasma content in the retina. NPDR is followed by pathological neovascularization and further neuronal degeneration. Dyslipidemia is a RD risk factor independent of hyperglycemia. We analyze the consequence of lipid plasma retinal extravasion on the activation of Mononuclear phagocyte (MP) and glial cells. We aim at (i) characterizing the molecular mechanisms linking lipid-derived activation of MP and glia to vascular remodeling, (ii) at identifying plasma pathogenic lipids specific of DR patients and (iii) developing innovative therapy to normalize lipid-derived MP and glial activation.

Non-infectious uveitis (Cécile Delarasse)

Non-infectious uveitis is an inflammatory pathology of the eye that affects the uvea (anterior and intermediate uveitis) but also the retina (posterior uveitis). Both innate and adaptive immune systems are involved in the pathological processes. Our aim is 1) to identify and validate new therapeutic targets using animal models of autoimmune uveitis, 2) to understand the specific mechanisms of recruitment and activation of microglia (MC) and mononuclear phagocyte (MP) in the retina during uveitis, and 3) to characterize the immune response in a prospective cohort study of patients with non-infectious uveitis.