Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lacking Dusp4
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 used 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 showed reduced optomotor responses, increased ON-bipolar cell depolarization, reduced oscillatory potentials together with altered OFF and ON-OFF retinal ganglion cell responses to light flashes. These data provide insights into retina-driven mechanisms of myopization, nuancing the impact of ON and OFF pathways upon emmetropization.
Authors
- Marie-Laure Gimenez
- Robert M. Duvoisin (ORCID: https://orcid.org/0000-0001-9603-7948)
- Jacques Callebert (ORCID: https://orcid.org/0000-0002-5622-851X)
- Juliette Varin (ORCID: https://orcid.org/0000-0002-6842-9757)
- Isabelle S. Audo (ORCID: https://orcid.org/0000-0003-0698-5309)
- Catherine W. Morgans (ORCID: https://orcid.org/0000-0002-7287-3447)
- Saïd El Shamieh (ORCID: https://orcid.org/0000-0002-8522-0445)
- Baptiste Wilmet (ORCID: https://orcid.org/0009-0003-0058-0199)
- Olivier Marre (ORCID: https://orcid.org/0000-0002-0090-6190)
- Christelle Michiels (ORCID: https://orcid.org/0000-0002-7193-5642)
- Helen Frederiksen
- Linda Horan
- Robin J. Plevin (ORCID: https://orcid.org/0000-0002-7849-1220)
- Christina Zeitz (ORCID: https://orcid.org/0000-0002-3510-1712)
- Serge A. Picaud (ORCID: https://orcid.org/0000-0002-0548-5145)
- Awen Louboutin (ORCID: https://orcid.org/0009-0001-2587-3495)
- Jingyi Zhang
- Sanja Boranijasevic (ORCID: https://orcid.org/0009-0009-2191-0007)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut de la Vision (FR)
- Inserm (FR)
- Oregon Health & Science University (US)
- University of Strathclyde (GB)
- Centre hospitalier national d'ophtalmologie des Quinze-Vingts (FR)
- Beirut Arab University (LB)
- Sorbonne Université (FR)
- Hôpital Lariboisière (FR)
- Marqueurs cardiovasculaires en situation de stress (FR)
Publication Details
- Journal
- Communications Biology
- Published
- 2026-09-29
- DOI
- https://doi.org/10.1038/s42003-026-11009-x
- Primary Topic
- Ophthalmology and Visual Impairment Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00