期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms22094877
关键词
CDSRR; cone-rod dystrophy; KCNV2; KCNB1; voltage-gated potassium channels; photoreceptors; retinal degeneration
资金
- Department of Health WA Merit Awards 2016-17
- Lions Eye Institute
- UWA Postgraduate Award International Students
- RTP International Fees Offset Scholarships
Loss of Kv8.2 subunits in murine retina contributes to early cellular and physiological changes leading to retinal dysfunction.
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 pathophysiology. 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 modulatory 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.
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