Related Experiment Video

Updated: Jan 27, 2026

Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium Cells: A Disease-in-a-dish Model for BEST1 Mutations
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Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium Cells: A Disease-in-a-dish Model for BEST1 Mutations

Published on: August 24, 2018

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Disease-associated mutations of claudin-19 disrupt retinal neurogenesis and visual function

Shao-Bin Wang1,2,3, Tao Xu1,2,4, Shaomin Peng4

  • 11Department of Surgery, Yale University, PO Box 208062, New Haven, CT USA.

Communications Biology
|April 3, 2019
PubMed

Insights

Mutations in claudin-19 disrupt retinal development and function, leading to ocular disease. Restoring a key molecule partially improved vision in mouse models, highlighting claudin-19

Area of Science:

  • Ophthalmology
  • Genetics
  • Cell Biology

Background:

  • Familial Hypomagnesaemia and Hypercalciuria with Ocular Involvement is linked to claudin-19 mutations.
  • Studying ocular manifestations requires isolating them from renal complications.

Purpose of the Study:

  • To investigate the specific role of claudin-19 mutations in ocular disease.
  • To understand the impact of these mutations on retinal development and function.

Main Methods:

  • Recreating human CLDN19 point mutations in induced pluripotent stem cells.
  • Overexpressing wild-type and mutant CLDN19 in newborn mouse retinae.
  • Utilizing electroretinography and histological analysis in mouse models.
  • Assessing RPE signature gene expression in cell lines.

Main Results:

  • Claudin-19 mutations impaired retinal neurogenesis and RPE maturation in cell models.
  • Mouse models showed reduced electroretinogram P1 waves, outer nuclear layer apoptosis, and altered bipolar cell morphology.
  • Partial restoration of the P1 wave was observed with 9-cis-retinal administration.
  • Exogenous wild-type claudin-19, but not mutant, enhanced RPE signature gene expression.

Conclusions:

  • Mutated claudin-19 significantly affects RPE and retinal differentiation.
  • The study elucidates the molecular mechanisms underlying claudin-19-associated ocular pathology.
  • Targeting specific pathways may offer therapeutic potential for these genetic eye diseases.

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