Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lacking Dusp4
Wilmet, B.; Michiels, C.; Zhang, J.; Louboutin, A.; Boranijasevic, S.; Frederiksen, H.; Callebert, J.; Varin, J.; Gimenez, M. L.; Morgans, C. W.; Duvoisin, R.; Horan, L.; Plevin, R.; Picaud, S.; Marre, O.; Audo, I.; Zeitz, C.
Show abstract
Myopia, 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.
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