Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1

•Prolonged phototransduction signaling prompts activation of retinal microglia.•Microglial phagocytosis precedes classical measures of retinal degeneration.•Increased OCT light scatter provides novel method for detecting cell stress in vivo.

Microglia dynamically prune synaptic contacts during development, and digest waste that accumulates in degeneration and aging. In many neurodegenerative diseases, microglial activation and phagocytosis gradually increase over months or years, with poorly defined initial triggering events. Here, we describe rapid retinal microglial activation in response to physiological light levels in a mouse model of photoreceptor degeneration that arises from defective rhodopsin deactivation and prolonged signaling. Activation, migration and proliferation of microglia proceeded along a well-defined time course apparent within 12 h of light onset. Retinal imaging in vivo with optical coherence tomography revealed dramatic increases in light-scattering from photoreceptors prior to the outer nuclear layer thinning classically used as a measure of retinal neurodegeneration. This model is valuable for mechanistic studies of microglial activation in a well-defined and optically accessible neural circuit, and for the development of novel methods for detecting early signs of pending neurodegeneration in vivo.

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