| Autor: |
Maria E. Mercau, Yemsratch T. Akalu, Francesca Mazzoni, Gavin Gyimesi, Emily Alberto, Yong Kong, Brian P. Hafler, Silvia C. Finnemann, Carla V. Rothlin, Sourav Ghosh |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.10.08.511415 |
| Popis: |
Severe, early-onset photoreceptor (PR) degeneration associated withMERTKmutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models ofMertkablation is determined by the hypomorphic expression or the loss of theMertkparalogTyro3. Here we find that loss ofMertkand reduced expression/loss ofTyro3led 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 inMertk-/-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 withMertkloss of function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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