Background: Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we examined the involvement of myosin 1f as a key regulator of immune cell activation via the AKT and MAPK pathways in microglia.
Methods: We chose retinal detachment as the model of photoreceptor degeneration. Immunofluorescence and Western Blot was performed to confirm the expression and location of myosin 1f in detached retina. The RD mouse model was induced in WT and myosin 1f-/- mice and confirmed by HE and TUNEL staining. The expression of inflammatory cytokine and downstream pathways was assessed via qPCR and WB.
Results: Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against cell death by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways.
Conclusions: Myosin 1f plays a crucial role in microglia-induced neuro-inflammation after retinal injury and photoreceptor degeneration by regulating 2 classic pathways, MAPK and AKT, and thereby decreasing the expression of inflammatory cytokines. Myosin 1f can be inhibited to prevent a decline in visual acuity after photoreceptor degeneration.
