Tandem pore domain acid-sensitive K channel 3 (TASK-3) regulates visual sensitivity in healthy and aging retina

Retinal ganglion cells (RGCs) not only collect but also integrate visual signals and send them from the retina to the brain. The mechanisms underlying the RGC integration of synaptic activity within retinal circuits have not been fully explored. Here, we identified a pronounced expression of tandem pore domain acid-sensitive potassium channel 3 (TASK-3), a two-pore domain potassium channel (K2P), in RGCs. By using a specific antagonist and TASK-3 knockout mice, we found that TASK-3 regulates the intrinsic excitability and the light sensitivity of RGCs by sensing neuronal activity-dependent extracellular acidification. In vivo, the blockade or loss of TASK-3 dampened pupillary light reflex, visual acuity, and contrast sensitivity. Furthermore, overexpressing TASK-3 specifically in RGCs using an adeno-associated virus approach restored the visual function of TASK-3 knockout mice and aged mice where the expression and function of TASK-3 were reduced. Thus, our results provide evidence that implicates a critical role of K2P in visual processing in the retina.