Back to Search
Start Over
Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 4877, p 4877 (2021), International Journal of Molecular Sciences, Volume 22, Issue 9
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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 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.
- Subjects :
- 0301 basic medicine
Retinal degeneration
Aging
chemistry.chemical_compound
0302 clinical medicine
Shab Potassium Channels
CDSRR
cone-rod dystrophy
Gliosis
Biology (General)
Spectroscopy
KCNB1
Mice, Knockout
Cell Death
photoreceptors
General Medicine
Voltage-gated potassium channel
Computer Science Applications
Cell biology
Chemistry
medicine.anatomical_structure
Potassium Channels, Voltage-Gated
Microglia
Erg
Cone dystrophy with supernormal rod response
QH301-705.5
Protein subunit
KCNV2
Biology
Catalysis
Article
Retina
Inorganic Chemistry
03 medical and health sciences
voltage-gated potassium channels
medicine
Electroretinography
Animals
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Night Vision
Voltage-gated ion channel
Organic Chemistry
Immunity
Retinal
medicine.disease
Protein Subunits
030104 developmental biology
chemistry
030221 ophthalmology & optometry
retinal degeneration
sense organs
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 4877
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....e0a2cb2cbe45b7e4bb5795ffc016f0ad