AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa

BioRxiv : the Preprint Server for Biology
Y. XueConstance L Cepko

Abstract

Retinitis pigmentosa (RP) is an inherited retinal disease, affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a gene-agnostic therapy, we screened {approx}20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus (AAV) vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb), and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.

Related Concepts

Gene Therapy
Genes
Lactate Dehydrogenase
Mitochondria
Persons
Retinal Diseases
Retinitis Pigmentosa
Thioredoxins
Vision
Visual Acuity

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