Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lacking Dusp4.
Baptiste Wilmet, Christelle Michiels, Jingyi Zhang, Awen Louboutin, Sanja Boranijasevic, Helen Frederiksen, Jacques Callebert, Juliette Varin, Marie-Laure Gimenez, Catherine Morgans, Robert Duvoisin, Linda Horan, Robin Plevin, Serge Picaud, Olivier Marre
Abstract
Open AccessMyopia, influenced by environmental and genetic factors, occurs when the emmetropization process fails to stop, causing excessive eyeball growth. Highly myopic animal models lacking a functional ON-pathway identified Dusp4 as a potential gene implicated in myopia. Here, we use a mouse model lacking DUSP4 to gain a better understanding of its retinal role and the mechanisms implicated in myopia development. Dusp4 -/- mice have a reduced basal level of retinal dopamine and a higher susceptibility to lens-induced myopia. Dusp4 is expressed in ON-bipolar cells and a subset of OFF-bipolar cells in a light dependent manner. The absence of DUSP4 causes a hyperactivation of the MAPK/ERK pathway. Dusp4 -/- mice show a reduced optomotor response, increased ON-bipolar cell responses, reduced oscillatory potentials together with altered OFF and ON-OFF RGC response to light flashes. These data provide new insights into retina-driven mechanisms of myopization, nuancing the impact of ON and OFF pathways upon emmetropization.