
Project description
The embryonic eye is nourished and oxygenated by transient fetal vessels called hyaloids, which regress after birth to be replaced by permanent retinal blood vessels. When this hyaloid regression process is lacking, we see diseases characterized by abnormal retinal development with congenital blindness which accounts for about 5% of vision loss in children. These rare retinopathies caused by the persistence of hyaloid vessels at birth are characterized by a spectrum of vascular changes in the retina at birth that progress during childhood or adolescence to cause varying degrees of visual impairment. This is the case with Norrie’s disease (ND), persistent hyperplastic primary vitreous (PHPV), familial exudative vitreoretinopathy (RVEF) and coats disease. Mutations associated with these rare retinopathies have been identified in a family of genes (NDP, FRZ4, LRP5, TSPAN12) which encode proteins playing a key role in vascular development of the eye, inner ear and brain. . These symptoms may resemble other orphan diseases (eg CHARGE syndrome).
These diseases are associated with a severe defect in retinal vascularity, so it is imperative to understand vascular development in the eye very early in embryonic development. The ultimate goal of this program is to identify the embryonic cells that form the blood vessels of the retina, as well as the molecules that direct their proliferation, migration and differentiation. This information will help us better understand and treat rare eye diseases affecting the sight of children of different ages. I recently discovered a new mechanism of premature senescence (premature aging) of retinal cells in our mouse model (oxygen-induced retinopathy) mimicking retinopathy of prematurity in humans. Currently, my collaborators and I are exploring a very promising therapeutic route to treat this rare retinopathy. Our goal is to reverse the process of premature aging affecting the retina in retinopathy of prematurity and other rare retinopathies.
Current treatment strategies include laser photocoagulation or surgical removal of the vitreous (early vitrectomy). Admittedly, these interventions allow an improvement of the vision by stopping the progress of the disease but the disease persists hence the urgency and the need to develop new therapeutic strategies. The discovery of new molecular markers for these rare diseases will help not only the correct diagnosis but also the development of effective therapies improving the eyesight of these patients. These objectives are in perfect harmony with the primary mission of our research center on orphan diseases and meet the guidelines of CERMO-FC.
Laboratory
Laboratory of Pr Malika Oubaha (UQAM)
Laureate: 2019 teaching allowance