| First Author | Collin GB | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 4 | PubMed ID | 35216333 |
| Mgi Jnum | J:321062 | Mgi Id | MGI:6883646 |
| Doi | 10.3390/ijms23042220 | Citation | Collin GB, et al. (2022) A splicing mutation in Slc4a5 results in retinal detachment and retinal pigment epithelium dysfunction. Int J Mol Sci 23(4):2220 |
| abstractText | Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer bloodâretinal barrier. Characterizing these transporters and their role in retinal homeosta-sis 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 sequenc-ing of tvrm77 mice revealed a disrupted 5â 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, hypopig-mented 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 ï¬uid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer bloodâretinal barrier. |
