A Potential Neuroprotective Role for Pyruvate Kinase 2 in Retinal Degeneration

Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment that specific therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of the targets, namely, pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors' well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in different RP mouse models via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. This observation provides supportive evidence that PKM2 may serve as a novel potential molecular target in RP.