Document Type

Article

Publication Date

2-17-2022

Publication Title

Int J Mol Sci

Keywords

JMG

JAX Source

Int J Mol Sci 2022 Feb 17; 23(4):2220

Volume

23

Issue

4

ISSN

1422-0067

PMID

35216333

DOI

https://doi.org/10.3390/ijms23042220

Abstract

Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood-retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5' splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood-retinal barrier.

Comments

The authors thank Lisa Stone and Jeannie Hansen for assisting with mouse breeding and colony maintenance. We also thank Jim Peterson for helping with Excel analysis.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

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