Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa

Journal of Clinical Medicine
Spencer M MooreDaniel L Chao

Abstract

Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described with autosomal dominant, autosomal recessive, and X-linked inheritance and sporadic mutations. The diversity of mutations makes gene therapy challenging, highlighting the need for mutation-agnostic treatments. Neural leucine zipper (NRL) and NR2E3 are factors important for rod photoreceptor cell differentiation and homeostasis. Germline mutations in NRL or NR2E3 leads to a loss of rods and an increased number of cones with short wavelength opsin in both rodents and humans. Multiple groups have demonstrated that inhibition of NRL or NR2E3 activity in the mature retina could endow rods with certain properties of cones, which prevents cell death in multiple rodent RP models with diverse mutations. In this review, we summarize the literature on NRL and NR2E3, therapeutic strategies of NRL/NR2E3 modulation in preclinical RP models, as well as future directions of research. In summary, inhibition of the NRL/NR2E3 pathway repr...Continue Reading

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Citations

Apr 15, 2021·Klinische Monatsblätter für Augenheilkunde·Anna FriesacherMargarita G Todorova

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Methods Mentioned

BETA
electron microscopy
gene knockout
antisense oligonucleotide

Clinical Trials Mentioned

NCT02384293
NCT02464436
NCT03073733
NCT03944239
NCT02320812
NCT04278131
NCT03326336
NCT02556736

Software Mentioned

jCyte

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