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.
Conseil scientifique : AVIS et RAPPORT relatif à la Crédibilité de l’expertise scientifique link
Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches. Daruich A, Duncan M, Robert MP, Lagali N, Semina EV, Aberdam D, Ferrari S, Romano V, des Roziers CB, Benkortebi R, De Vergnes N, Polak M, Chiambaretta F, Nischal KK, Behar-Cohen F, Valleix S, Bremond-Gignac D.Prog Retin Eye Res. 2023 Jul;95:101133. link
Single mRNA detection of Wnt signaling pathway in the human limbus. Bonnet C, Ruiz M, Gonzalez S, Tseng CH, Bourges JL, Behar-Cohen F, Deng SX. Exp Eye Res. 2023 Apr;229:109337. doi: 10.1016/j.exer.2022.109337. Epub 2023 Jan 23. PMID: 36702232 Free article. link
Optical Coherence Tomography Angiography Assessment in Congenital Aniridia. Dentel A, Ferrari M, Robert MP, Valleix S, Bremond-Gignac D, Daruich A. Am J Ophthalmol. 2023 Apr 13;253:44-48. link
High Levels of C-Reactive Protein with Low Levels of Pentraxin 3 as Biomarkers for Central Serous Chorioretinopathy. Bousquet E, Chenevier-Gobeaux C, Jaworski T, Torres-Villaros H, Zola M, Mantel I, Kowalczuk L, Matet A, Daruich A, Zhao M, Yzer S, Behar-Cohen F. Ophthalmol Sci. 2023 Feb 3;3(3):100278. doi: 10.1016/j.xops.2023.100278. eCollection 2023 Sep. PMID: 36950301 Free PMC article. link
A mathematical model of wound healing in bovine corneal endothelium. Hernández JA, Chifflet S, Justet C, Torriglia A. J Theor Biol. 2023 Feb 21;559:111374. link
Early treatment of neonatal diabetes with oral glibenclamide in an extremely preterm infant. Galderisi A, Kermorvant-Duchemin E, Daruich A, Bonnard AA, Lapillonne A, Aubelle MS, Perrella B, Vial Y, Cave H, Berdugo M, Jarreau PH, Polak M, Beltrand J. JIMD Rep. 2023 Jan 29;64(2):161-166. link
Retinoblastoma: From genes to patient care. Bouchoucha Y, Matet A, Berger A, Carcaboso AM, Gerrish A, Moll A, Jenkinson H, Ketteler P, Dorsman JC, Chantada G, Beck-Popovic M, Munier F, Aerts I, Doz F, Golmard L; European Retinoblastoma Group EuRbG. Eur J Med Genet. 2023 Jan;66(1):104674 link
In Vivo Retinal Pigment Epithelium Imaging using Transscleral Optical Imaging in Healthy Eyes. Kowalczuk L, Dornier R, Kunzi M, Iskandar A, Misutkova Z, Gryczka A, Navarro A, Jeunet F, Mantel I, Behar-Cohen F, Laforest T, Moser C. Ophthalmol Sci. 2022 Oct 19;3(1):100234. doi: 10.1016/j.xops.2022.100234. eCollection 2023 Mar. PMID: 36545259 link
Ophthalmological Impairments at Five and a Half Years after Preterm Birth: EPIPAGE-2 Cohort Study. Chapron T, Pierrat V, Caputo G, Letouzey M, Kermorvant-Duchemin E, Abdelmassih Y, Beaumont W, Barjol A, Le Meur G, Benhamou V, Marchand-Martin L, Ancel PY, Torchin H. J Clin Med. 2022 Apr 11;11(8):2139. link
Venous overload choroidopathy: A hypothetical framework for central serous chorioretinopathy and allied disorders. Spaide RF, Gemmy Cheung CM, Matsumoto H, Kishi S, Boon CJF, van Dijk EHC, Mauget-Faysse M, Behar-Cohen F, Hartnett ME, Sivaprasad S, Iida T, Brown DM, Chhablani J, Maloca PM. Prog Retin Eye Res. 2022 Jan;86:100973. link
Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model. Alejandra Daruich, Thara Jaworski, Hugues Henry, Marta Zola, Jenny Youale, Léa Parenti, Marie-Christine Naud, Kimberley Delaunay, Mathilde Bertrand, Marianne Berdugo, Laura Kowalczuk, Jeffrey Boatright, Emilie Picard & Francine Behar-Cohen. Neurotherapeutics 2021. Apr;18(2):1325-1338. doi: 10.1007/s13311-021-01009-6. link
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. link
The antidiabetic drug glibenclamide exerts direct retinal neuroprotection. Berdugo M, Delaunay K, Naud MC, Guegan J, Moulin A, Savoldelli M, Picard E, Radet L, Jonet L, Djerada Z, Gozalo C, Daruich A, Beltrand J, Jeanny JC, Kermorvant-Duchemin E, Crisanti P, Polak M, Behar-Cohen F. Transl Res. 2020 Oct 17:S1931-5244(20)30244-9. doi: 10.1016/j.trsl.2020.10.003. link
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 link
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. link
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. linkAll publications