Mouse NR2E3R296Q Mutation Disrupts Photoreceptor Developmental Paradigm and Leads to Early‐Onset Progressive Retinal Degeneration by Suppressing RXRG Signaling DOI Creative Commons
Jiacheng Jin, Shuai Wang, Yinjiu Huang

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(9)

Опубликована: Май 3, 2025

ABSTRACT The NR2E3 R311Q mutation can lead to retinitis pigmentosa, enhanced S‐cone syndrome (ESCS), Goldmann–Favre syndrome, and clumped pigmentary retinal degeneration. relationship between this various recessive inherited degenerative disorders is unclear complicates clinical diagnosis treatment. In study, we generated a mouse strain carrying the R296Q using CRISPR/Cas9 technology simulate in humans investigate influence of missense on photoreceptor developmental profile maintenance. Retinal architecture lamination were normal mice. Whorls rosettes not observed outer nuclear layer (ONL). Rod cell quantity developed normally, whereas small amount Rhodopsin was incorrectly located ONL. Blue cones excessively produced at dorsal retina, green cone development normal. Colocalization Arrestin occurred retinas Heterozygous +/R296Q mice showed no evident abnormalities structure or development. Retinas underwent progressive degeneration starting early postnatal stage, which manifested as reduced ONL thickness segment fragmentation. where redundant blue are generated, degenerated more advanced manner. At molecular level, bound directly RXRG promoter, significantly impaired binding, resulting decreased mRNA protein expressions. summary, novel model exhibiting an ESCS‐like phenotype, thus providing NR2E3‐RXRG signaling pathway for modulating

Язык: Английский

Insights into eye genetics and recent advances in ocular gene therapy DOI Creative Commons
Viktória Szabó, Balázs Varsányi,

Mirella Telles Salgueiro Barboni

и другие.

Molecular and Cellular Probes, Год журнала: 2025, Номер 79, С. 102008 - 102008

Опубликована: Янв. 18, 2025

Язык: Английский

Процитировано

3
From bench to bedside: Developing CRISPR/Cas-based therapy for ocular diseases DOI Creative Commons
Qing Zhao, L. J. Wei, Youxin Chen

и другие.

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107638 - 107638

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

3
Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study DOI Creative Commons
Michel Michaelides, Yannik Laich, Sui Chien Wong

и другие.

The Lancet, Год журнала: 2025, Номер 405(10479), С. 648 - 657

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

3
The value of genetic testing in pediatric and adult ophthalmology DOI Creative Commons
Ulrich Kellner,

Simone Kellner,

Silke Weinitz

и другие.

Medizinische Genetik, Год журнала: 2025, Номер 37(1), С. 11 - 18

Опубликована: Фев. 6, 2025

Язык: Английский

Процитировано

1
Natural remedies proposed for the management of diabetic retinopathy (DR): diabetic complications DOI Creative Commons
Emad Gamil Khidr,

Nourhan Ibrahim Morad,

Shymaa Hatem

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Abstract Diabetic retinopathy (DR) represents a significant and serious complication associated with diabetes mellitus (DM), often resulting in considerable visual impairment or even blindness. The intricate pathological processes underlying DR complicate the effectiveness of current treatment modalities. Studies have highlighted potential natural products via several beneficial effects including anti-inflammatory, antioxidant, anti-neovascular, anti-apoptotic properties. Flavonoids, saponins, saccharides, alkaloids exhibited various vivo vitro studies. However, clinical utilization these compounds is hindered by issues such as inadequate specificity, low bioavailability, toxicity. Therefore, there pressing need for rigorous studies to confirm efficacy preventing mitigating progression DR.

Язык: Английский

Процитировано

1
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review DOI Creative Commons

Wendy M. Wong,

Omar A. Mahroo

Clinical and Experimental Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Phototransduction, the process by which captured photons elicit electrical changes in retinal rod and cone cells, represents first neuronal step vision involves interactions between several highly specialised proteins. Pathogenic variants genes encoding many of these proteins can give rise to significant impairment, accounting for a substantial portion inherited disease. Such include RHO, OPN1LW, OPN1MW, GNAT1, GNAT2, GNB3, PDE6A, PDE6B, PDE6G, PDE6C, PDE6H, CNGA1, CNGB1, CNGA3, CNGB3, GRK1, SAG, ARR3, RGS9, RGS9BP, GUCY2D, GUCA1A SLC24A1. Many conditions have distinct mechanisms clinical features. They follow modes inheritance (including one case digenic, or tri-allelic, inheritance). Some also entail myopia. Rod phototransduction will be outlined, followed discussion diseases associated with genes. phenotypic features highlighted as well their prevalence large genotyped disease cohort.

Язык: Английский

Процитировано

1
In vivo prime editing rescues photoreceptor degeneration in nonsense mutant retinitis pigmentosa DOI Creative Commons

Yidian Fu,

Xiaoyu He,

Liang Ma

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 10, 2025

The next-generation gene editing tool, prime (PE), is adept at correcting point mutations precisely with high efficiency and rare off-target events shows promising therapeutic value in treating hereditary diseases. Retinitis pigmentosa (RP) the most common type of inherited retinal dystrophy characterized by progressive degeneration photoreceptors and, consequently, visual decline. To date, effective treatments for RP are lacking. Herein, a PE system designed to target PDE6B Y347X mutation rd1 mouse strain, preclinical model. We screen develop epegRNA RTΔRnH, which delivered via dual-AAV vivo an 26.47 ± 13.35%, negligible effects confirmed AID-Seq PE-tag. Treatment greatly restores protein expression protects rod cells from degeneration. Mouse behavioural experiments also show that compared no treatment, inhibits vision deterioration littermate mice. This study provides opportunity use correct mutated RPs genomic level. without treatments. Here, authors apply (PE) In treatment achieves genome mice vision.

Язык: Английский

Процитировано

1
A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort DOI Creative Commons
Mukhtar Ullah, Atta Ur Rehman, Mathieu Quinodoz

и другие.

npj Genomic Medicine, Год журнала: 2025, Номер 10(1)

Опубликована: Апрель 4, 2025

Язык: Английский

Процитировано

1
Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom DOI Open Access
William Woof, Thales A. C. de Guimarães, Saoud Al‐Khuzaei

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

Abstract Purpose To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Design Retrospective study imaging data (55-degree blue-FAF on Heidelberg Spectralis) from Participants Patients with clinical molecularly confirmed diagnosis IRD who have undergone FAF 55-degree at Moorfields Eye Hospital (MEH) the Royal Liverpool (RLH) between 2004 2019. Methods Five interest were defined: vessels, optic disc, perimacular ring increased signal (ring), relative hypo-autofluorescence (hypo-AF) hyper-autofluorescence (hyper-AF). Features manually annotated by six graders subset patients based defined grading protocol to produce segmentation masks train an AI model, AIRDetect, which was then applied entire MEH dataset. Main Outcome Measures Quantitative including area mm 2 vessel metrics, analysed gene age, determine rate progression. AIRDetect feature detection validated Dice score precision/recall, respectively. Results A total 45,749 images 3,606 covering 170 genes automatically segmented using AIRDetect. Model-grader scores for hypo-AF, hyper-AF, vessels respectively 0.86, 0.72, 0.69, 0.68 0.65. The five largest hypo-AF areas CHM , ABCC6 ABCA4 RDH12 RPE65 mean per-patient 41.5, 30.0, 21.9, 21.4, 15.1 . hyper-AF BEST1 CDH23 MYO7A NR2E3 0.49, 0.45, 0.44, 0.39, 0.34 CRX EYS MYO7A, 3.63, 3.32, 2.84, 2.39, 2.16 Vessel density found be highest EFEMP1 TIMP3 RS1 PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) lower Retinitis Pigmentosa (RP) Leber Congenital Amaurosis genes. Longitudinal analysis decreasing four RP ( RPGR, USH2A, RHO, ) fastest progressor -0.18 /year. Conclusions We conducted first large-scale cross-sectional longitudinal quantitative across diverse range IRDs novel approach.

Язык: Английский

Процитировано

5
Retinal Imaging Findings in Inherited Retinal Diseases DOI Open Access
Giulia Corradetti, Aditya Verma, Jasaman Tojjar

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(7), С. 2079 - 2079

Опубликована: Апрель 3, 2024

Inherited retinal diseases (IRDs) represent one of the major causes progressive and irreversible vision loss in working-age population. Over last few decades, advances imaging have allowed for an improvement phenotypic characterization this group facilitated phenotype-to-genotype correlation studies. As a result, number clinical trials targeting IRDs has steadily increased, commensurate to this, need novel reproducible outcome measures endpoints grown. This review aims summarize describe presentation, characteristic findings, endpoint that are being used research on IRDs. For purpose review, been divided into four categories: (1) panretinal pigmentary retinopathies affecting rods or cones; (2) macular dystrophies; (3) stationary conditions; (4) hereditary vitreoretinopathies.

Язык: Английский

Процитировано

4