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- W4303673939 abstract "Abstract Severe, early-onset photoreceptor (PR) degeneration associated with MERTK mutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models of Mertk ablation is determined by the hypomorphic expression or the loss of the Mertk paralog Tyro3 . Here we find that loss of Mertk and reduced expression/loss of Tyro3 led to RPE inflammation even before eye-opening. Incipient RPE inflammation cascaded to involve microglia activation and PR degeneration with monocyte infiltration. Inhibition of RPE inflammation with the JAK1/2 inhibitor ruxolitinib mitigated PR degeneration in Mertk -/- mice. Neither inflammation nor severe, early-onset PR degeneration were observed in mice with defective phagocytosis alone. Thus, inflammation drives severe, early-onset PR degeneration-associated with Mertk loss of function." @default.
- W4303673939 created "2022-10-08" @default.
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- W4303673939 date "2022-10-08" @default.
- W4303673939 modified "2023-09-23" @default.
- W4303673939 title "Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in<i>Mertk</i>-associated retinitis pigmentosa" @default.
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- W4303673939 doi "https://doi.org/10.1101/2022.10.08.511415" @default.
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