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

Y Xue, SK Wang, P Rana, ER West, CM Hong, H Feng… - elife, 2021 - elifesciences.org
Y Xue, SK Wang, P Rana, ER West, CM Hong, H Feng, DM Wu, CL Cepko
elife, 2021elifesciences.org
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 disease gene-agnostic therapy, we screened 20 genes for
their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno …
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 disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus 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.
eLife