Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lacking Dusp4
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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.
Significance Statement
Light and retinal signaling is involved in the protection and development of myopia since the retina detects the sign and extent of optical defocus and informs the surrounding tissues when growth processes have to stop. Nevertheless, these precise mechanisms are still poorly understood. By studying a genetic model lacking Dusp4 we show that both, the ON but also the OFF pathway is important for the protection and development of myopia and that these mechanisms are most likely regulated by light. Thus, our findings integrate, within a single study, key factors such as light, retinal signaling, and genetics in the protection against and development of myopia.
