Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

Significance Recent evidence suggests human retinal Müller glia retain a potential for neuronal regeneration. Defining the mechanisms governing retinal repair in robustly regenerative species may provide insights for harnessing this potential therapeutically. Here, we investigated roles of the innate immune system during rod photoreceptor regeneration in zebrafish. Our data establish a role for retinal microglia, the tissue-resident macrophage of the retina, in regulating retinal Müller glia responsiveness to cell death, and thereby controlling photoreceptor regeneration kinetics. Further, we show that immunosuppression can either inhibit or accelerate photoreceptor regeneration kinetics depending on the timing of treatment. We conclude that modulation of immune cell responses to retinal neuron cell death stands as a promising strategy for promoting repair of the human eye.