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bioRxiv · 10.1101/2021.01.27.428411

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

Xue, Y.·Wang, S. K.·Rana, P.·West, E. R.·Hong, C. M.·Feng, H.·Wu, D. M.·Cepko, C. L.
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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.

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Xue, Y., Wang, S. K., Rana, P., West, E. R., Hong, C. M., Feng, H., Wu, D. M., Cepko, C. L.. 2021-01-27. AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa. https://doi.org/10.1101/2021.01.27.428411

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