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Learning from Fifteen Years of Genome-Wide Association Studies in Age-Related Macular Degeneration
Open AccessArticle

A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells

1
Institut de la Vision, Sorbonne Université, INSERM, CNRS, 17 rue Moreau, F-75012 Paris, France
2
CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, 28 rue de Charenton, F-75012 Paris, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cells 2021, 10(1), 179; https://doi.org/10.3390/cells10010179
Received: 10 December 2020 / Revised: 5 January 2021 / Accepted: 15 January 2021 / Published: 18 January 2021
(This article belongs to the Special Issue Molecular and Cellular Basis of Macular Degenerations)
Age-related macular degeneration (AMD) is a blinding disease for which most of the patients remain untreatable. Since the disease affects the macula at the center of the retina, a structure specific to the primate lineage, rodent models to study the pathophysiology of AMD and to develop therapies are very limited. Consequently, our understanding relies mostly on genetic studies highlighting risk alleles at many loci. We are studying the possible implication of a metabolic imbalance associated with risk alleles within the SLC16A8 gene that encodes for a retinal pigment epithelium (RPE)-specific lactate transporter MCT3 and its consequences for vision. As a first approach, we report here the deficit in transepithelial lactate transport of a rare SLC16A8 allele identified during a genome-wide association study. We produced induced pluripotent stem cells (iPSCs) from the unique patient in our cohort that carries two copies of this allele. After in vitro differentiation of the iPSCs into RPE cells and their characterization, we demonstrate that the rare allele results in the retention of intron 2 of the SLC16A8 gene leading to the absence of MCT3 protein. We show using a biochemical assay that these cells have a deficit in transepithelial lactate transport. View Full-Text
Keywords: retinal pigment epithelium; lactate transport; induced pluripotent stem cells; splicing; MCT3; age-related macular degeneration retinal pigment epithelium; lactate transport; induced pluripotent stem cells; splicing; MCT3; age-related macular degeneration
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MDPI and ACS Style

Klipfel, L.; Cordonnier, M.; Thiébault, L.; Clérin, E.; Blond, F.; Millet-Puel, G.; Mohand-Saïd, S.; Goureau, O.; Sahel, J.-A.; Nandrot, E.F.; Léveillard, T. A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells. Cells 2021, 10, 179. https://doi.org/10.3390/cells10010179

AMA Style

Klipfel L, Cordonnier M, Thiébault L, Clérin E, Blond F, Millet-Puel G, Mohand-Saïd S, Goureau O, Sahel J-A, Nandrot EF, Léveillard T. A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells. Cells. 2021; 10(1):179. https://doi.org/10.3390/cells10010179

Chicago/Turabian Style

Klipfel, Laurence; Cordonnier, Marie; Thiébault, Léa; Clérin, Emmanuelle; Blond, Frédéric; Millet-Puel, Géraldine; Mohand-Saïd, Saddek; Goureau, Olivier; Sahel, José-Alain; Nandrot, Emeline F.; Léveillard, Thierry. 2021. "A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells" Cells 10, no. 1: 179. https://doi.org/10.3390/cells10010179

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