Logo image
Back
Kv2.1/Kv8.2 Channels Regulate Fluid Homeostasis in the Outer Retina
Preprint   Open access

Kv2.1/Kv8.2 Channels Regulate Fluid Homeostasis in the Outer Retina

Joseph G Laird, James Soetedjo, Shivangi M Inamdar, Alex R Bock, Ehimenmen Ataman, Miles A Pufall, Bruce A Berkowitz and Sheila A Baker
bioRxiv
Cold Spring Harbor Laboratory
07/02/2026
DOI: 10.64898/2026.06.27.734996
PMCID: PMC13344989
PMID: 42427698
url
https://doi.org/10.64898/2026.06.27.734996View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Photoreceptor Kv2.1/Kv8.2 voltage-gated potassium channels carry an outward potassium current, helping to set the resting membrane potential and to shape dim light responses. Because potassium flux in the outer retina influences extracellular osmolarity and fluid distribution, we hypothesized that Kv2.1/Kv8.2 channels also contribute to fluid homeostasis in this region of the retina. OCT imaging was performed in Kv8.2 heterozygous (Het) and knockout (KO) mice aged 4-7 weeks under dark- and light-adapted conditions. Light-dark differences in the distance between the external limiting membrane (ELM) and retinal pigment epithelium (RPE) (ΔELM-RPE) were calculated to quantify light-evoked expansion of the subretinal space (SRS). As a secondary outcome, outer nuclear layer (ONL) thickness was also measured under both lighting conditions. Retinal gene expression was assessed by RNA-seq and droplet digital RT-PCR. Retinal protein expression was determined by western blotting and immunolabeling. ΔELM-RPE was significantly reduced in Kv8.2 KO mice compared with Het controls, indicating reduced SRS hydration. ONL thickness exhibited a small but significant light-dark change that was different between genotypes. Transcriptomic analyses revealed upregulation of osmosensitive genes, including osmolyte transporters and aquaporins. AQP1 protein expression in photoreceptors increased. These findings reveal a previously unrecognized role for Kv2.1/Kv8.2 channels in outer retinal fluid homeostasis and support a model in which photoreceptor potassium efflux contributes to osmotic water movement into the subretinal space.

Details

Metrics

1 Record Views
Logo image