Physiopathology of ocular diseases: therapeutic innovations
Deputy Director :
The eye is made of transparent tissues that allows the proper transmission of photons towards photoreceptors that convert photons into electrical signal to the brain. Like the brain, the eye is protected by barriers that prevent systemic drug to reach the ocular tissues.
Whatever the primitive cause of disease, vision is lost through major common mechanisms leading to the loss of tissues transparency, death of visual cells and abnormal tissue reactions such as inflammation, fibrosis, and neovascularization.
Our team’s objectives are to identify key regulatory molecular targets involved in the pathogenesis of major mechanisms responsible for vision loss, accessible to modulation by drugs, administered locally, and applicable to diseases of various origins. Driven by unmet medical needs and innovation, we develop translational research.
The scientific questions underlying our work emerge from clinical problems. We also analyze the mechanisms of action of drugs commonly used in ophthalmology (i.e. anti-VEGF and corticoids), as well as the ocular risks of exposure to environmental burdens (i.e. light exposure).
The research performed by our team fulfills the gap between discovery and proof of concept in man. Valorization is considered for allowing further developments of the research conducted in the team.
The main mechanisms responsible for vision loss in ocular diseases are loss of transparency, fibroglial and neovascular proliferations and cell death. We study several regulatory pathways to control these vision threatening features.
Key words: eye, retina, ocular drug delivery, macular edema, oxidative stress, light, corticosteroids, ROCK kinase, SUR1, neuroprotection, therapeutic innovation, biomarkers
Mechanisms regulating tissue transparency
We develop targeted therapies aimed at restoring tissue integrity and optical quality, in particular for loss of transparency of the cornea or retina associated to various diseases.
We develop treatments that limit the deleterious consequences of oxidative, iron-induced, ischaemic, irradiation or metabolic and excitotoxic stress.
Biomarkers and drug delivery
In order to progress towards therapeutic trials, it is essential to select patients likely to respond to the different treatments developed on the basis of biomarkers of activity of the targeted pathways, to define biomarkers of efficacy and to develop methods for local targeting of drugs.
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Retinal phototoxicity and the evaluation of the blue light hazard of a new solid-state lighting technology.
Jaadane I, Villalpando Rodriguez G, Boulenguez P, Carré S, Dassieni I, Lebon C, Chahory S, Behar-Cohen F, Martinsons C, Torriglia A. Sci Rep. 2020 Apr 21;10(1):6733.
The antidiabetic drug glibenclamide exerts direct retinal neuroprotection.
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Transscleral Optical Phase Imaging of the Human Retina.
Laforest T, Künzi M, Kowalczuk L, Carpentras D, Behar-Cohen F, Moser C.Nat Photonics. 2020 Jul;14(7):439-445. doi: 10.1038/s41566-020-0608
Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.
Daruich A, Le Rouzic Q, Jonet L, Naud MC, Kowalczuk L, Pournaras JA, Boatright JH, Thomas A, Turck N, Moulin A, Behar-Cohen F, Picard E. Sci Adv. 2019 Jan 9;5(1):eaau9940.
Mineralocorticoid receptor antagonism limits experimental choroidalneovascularization and structural changes associated with neovascular age-related macular degeneration.
Zhao, M., et al., Nat Commun, 2019. 10(1): p. 369.