Dbouk, N. H.; Bagshaw, M.; Bose, A. A.; Rasdall, M.; Arner, A.; Zhao, K.; Taylor, K. E.; Praveen, N.; Huo, W.; Bautista, I.; Musayeva, N.; Xue, L.; Hayes, J. N.; McElhinney, M.; Bick, A. G.; Lea, A. J.; Rex, T. S.; Castiglione, G. M.

Visual sensitivity creates photodamage risk, a trade-off thought to limit photo-resilience. Here we reveal that the locus of sensitivity, the visual pigment rhodopsin, moonlights as a tunable mechanism of photoprotection. Light activated rhodopsin (R*) mitigates phototoxicity and boosts rod sensitivity by serving as an overflow capacitor buffering all-trans retinal (atRAL), a toxic and desensitizing retinoid agonist that accumulates as lipofuscin, a clinical marker of macular degeneration. We show that R* stability does not guarantee increased signaling as previously proposed. Instead, across mammals R* stability reflects atRAL binding affinity (capacitance) tuned by photodamage risk. R* capacitance affords cytoprotection and, counterintuitively, promotes dark adaptation by shielding neighboring dark-state receptors from agonist interference. We treated a mouse model of defective atRAL clearance with a synthetic R* of unnaturally high atRAL capacitance. This gene therapy preserved retinal function following light damage and provided supra-physiological scotopic sensitivity despite being a signal-silent receptor, modulating endogenous R* signaling. During recent human evolution, rhodopsin mutations that enhance capacitance and cytoprotection have emerged in high irradiance environments and are now significantly associated with a 36% reduced risk of blindness. Together, our findings redefine rhodopsin as a tunable light buffer that can be leveraged to enhance photoreceptor function beyond natural limits.