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

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 b...

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Autores principales: Moore, Spencer M., Skowronska-Krawczyk, Dorota, Chao, Daniel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408925/
https://www.ncbi.nlm.nih.gov/pubmed/32668775
http://dx.doi.org/10.3390/jcm9072224
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author Moore, Spencer M.
Skowronska-Krawczyk, Dorota
Chao, Daniel L.
author_facet Moore, Spencer M.
Skowronska-Krawczyk, Dorota
Chao, Daniel L.
author_sort Moore, Spencer M.
collection PubMed
description 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 represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP.
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spelling pubmed-74089252020-08-13 Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa Moore, Spencer M. Skowronska-Krawczyk, Dorota Chao, Daniel L. J Clin Med Review 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 represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP. MDPI 2020-07-13 /pmc/articles/PMC7408925/ /pubmed/32668775 http://dx.doi.org/10.3390/jcm9072224 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Moore, Spencer M.
Skowronska-Krawczyk, Dorota
Chao, Daniel L.
Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title_full Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title_fullStr Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title_full_unstemmed Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title_short Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
title_sort targeting of the nrl pathway as a therapeutic strategy to treat retinitis pigmentosa
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408925/
https://www.ncbi.nlm.nih.gov/pubmed/32668775
http://dx.doi.org/10.3390/jcm9072224
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