Colony-stimulating factor 1 receptor inhibition is neuroprotective to photoreceptors in retinal detachment

Retinal detachment (RD) triggers a neuroinflammatory response aimed at clearing damaged photoreceptors (PR) and limiting injury. However, this response can unintentionally worsen retinal neurodegeneration. Retinal microglia (MG) and infiltrating monocytes (Mø) play key roles in this process and are regulated by the colony-stimulating factor 1 receptor (CSF1R). Targeting the CSF1R has been proposed as a potential strategy to modulate neuroinflammation. Using PLX5622, a selective CSF1R inhibitor, we examined the local and systemic immune effects in RD in a novel experimental model with specific MG and Mø labeling. We found that PLX5622 depletes and alters the function of MG and Mø subtypes, modulates myeloid cell infiltration into the retina, and confers neuroprotection to PRs in both acute and chronic phases of RD. These findings highlight that CSF1R inhibition could create a therapeutic window to mitigate early inflammatory damage. Targeting CSF1R may represent a promising therapeutic strategy for neuroprotection in RD.