Molecular, cellular and functional changes in the retinas of young adult mice lacking the voltage-gated K+ channel subunits Kv8.2 and K2.1

Xiaotian Jiang, Rabab Rashwan, Valentina Voigt, Jeanne Nerbonne, David M. Hunt, Livia S. Carvalho

Research output: Contribution to journalArticlepeer-review

11 Citations (Web of Science)

Abstract

Cone Dystrophy with Supernormal Rod Response (CDSRR) is a rare autosomal recessive disorder leading to severe visual impairment in humans, but little is known about its unique patho-physiology. We have previously shown that CDSRR is caused by mutations in the KCNV2 (Potassium Voltage-Gated Channel Modifier Subfamily V Member 2) gene encoding the Kv8.2 subunit, a modula-tory subunit of voltage-gated potassium (Kv) channels. In a recent study, we validated a novel mouse model of Kv8.2 deficiency at a late stage of the disease and showed that it replicates the human electroretinogram (ERG) phenotype. In this current study, we focused our investigation on young adult retinas to look for early markers of disease and evaluate their effect on retinal morphology, electrophysiology and immune response in both the Kv8.2 knockout (KO) mouse and in the Kv2.1 KO mouse, the obligate partner of Kv8.2 in functional retinal Kv channels. By evaluating the severity of retinal dystrophy in these KO models, we demonstrated that retinas of Kv KO mice have significantly higher apoptotic cells, a thinner outer nuclear cell layer and increased activated microglia cells in the subretinal space. Our results indicate that in the murine retina, the loss of Kv8.2 subunits contributes to early cellular and physiological changes leading to retinal dysfunction. These results could have potential implications in the early management of CDSRR despite its relatively nonprogressive nature in humans.

Original languageEnglish
Article number4877
JournalInternational Journal of Molecular Sciences
Volume22
Issue number9
DOIs
Publication statusPublished - 1 May 2021

Fingerprint

Dive into the research topics of 'Molecular, cellular and functional changes in the retinas of young adult mice lacking the voltage-gated K+ channel subunits Kv8.2 and K2.1'. Together they form a unique fingerprint.

Cite this