Transcription co-repressors Panky and Panky-like are essential for retinal cone photoreceptor integrity and survival by modulating ganglioside metabolism

PPL DKO mice exhibited decreased light-evoked activities, impaired morphology of cone photoreceptors, and disrupted membrane integrity in the cone outer segments and synaptic terminals, followed by cone death at a later stage. RNA-seq analysis revealed that Cerkl gene, whose mutations in human ortholog CERKL cause retinitis pigmentosa (RP26), was upregulated in Panky/Panky-like/Nrl triple KO mouse retinas, in which loss of Nrl converts rods into cones.

Our findings suggest that the regulation of Cerkl expression in cone photoreceptors by Panky and Panky-like is essential for cone photoreceptor integrity and survival.