Mouse slc9a8 mutants exhibit retinal defects due to retinal pigmented epithelium dysfunction.

Area of Science:

• Ophthalmology
• Cell Biology
• Genetics

Background:

• Systematic genetic screens identify novel gene functions.
• The sodium/hydrogen ion exchanger NHE8 (encoded by Slc9a8) is essential for cellular homeostasis.
• Retinal structure and function depend on precise cellular processes.

Purpose of the Study:

• To characterize the retinal phenotype in mice lacking the Slc9a8 gene.
• To investigate the role of sodium/hydrogen ion exchange in retinal function.
• To determine the cellular basis of the observed retinal defects.

Main Methods:

• Histological analysis of mutant mouse retinas.
• Electroretinography (ERG) to assess retinal function.
• Utilizing a conditional Slc9a8 allele to pinpoint critical cell types.
• Analysis of endosomal morphology in mutant cells.

Main Results:

• Slc9a8 knockout mice display photoreceptor separation from the retinal pigment epithelium (RPE) and macrophage infiltration.
• ERG revealed deficits in both rod and cone pathway function.
• NHE8 function is critical specifically within RPE cells.
• Mutant RPE cells exhibit abnormal morphology and smaller recycling endosomes.

Conclusions:

• The NHE8 protein is essential in the RPE for regulating endosomal volume and/or pH.
• Proper endosomal regulation by NHE8 is vital for RPE cellular integrity.
• NHE8 deficiency in RPE leads to retinal dysfunction and pathology.