Сенсорные системы, Год журнала: 2023, Номер 37(3), С. 205 - 217
Опубликована: Июль 1, 2023
Язык: Английский
Medicina, Год журнала: 2024, Номер 60(1), С. 189 - 189
Опубликована: Янв. 22, 2024
Retinitis pigmentosa is an inherited disease, in which mutations different types of genes lead to the death photoreceptors and loss visual function. Although retinitis most common type retinal dystrophy, a clear line therapy has not yet been defined. In this review, we will focus on therapeutic aspect attempt define advantages disadvantages protocols therapies. The role some therapies, such as antioxidant agents or gene therapy, established for years now. Many clinical trials causing RP have conducted, approval voretigene nepavorec by FDA important step forward. Nonetheless, even if promising treatment these patients, other innovative strategies, stem cell transplantation hyperbaric oxygen shown be safe improve quality during trials. disease remains challenge, hope find solution soon possible.
Язык: Английский
Процитировано
12
International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(23), С. 15041 - 15041
Опубликована: Ноя. 30, 2022
Optogenetics is a recent breakthrough in neuroscience, and one of the most promising applications treatment retinal degenerative diseases. Multiple clinical trials are currently ongoing, less than decade after first attempt at visual restoration using optogenetics. Optogenetic therapy has great value providing hope for late-stage degeneration, regardless genotype. This alternative gene consists multiple elements including choice target cells, optogenetic tools, delivery systems. Currently, there various options each element, all which have been developed as product technological success. In particular, performance tools terms light wavelength sensitivity improved by engineering microbial opsins applying human opsins. To provide better post-treatment vision, optimal effective to cells necessary. this review, we an overview advancements restoration, focusing on available methods.
Язык: Английский
Процитировано
31
Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(17), С. 14946 - 14973
Опубликована: Июль 4, 2024
Inherited retinal diseases, which include retinitis pigmentosa, are a family of genetic disorders characterized by gradual rod-cone degeneration and vision loss, without effective pharmacological treatments. Experimental approaches aim to delay disease progression, supporting cones' survival, crucial for human vision. Histone deacetylases (HDACs) mediate the activation epigenetic nonepigenetic pathways that modulate cone in RP mouse models. We developed new HDAC inhibitors (5a–p), typified tetrahydro-γ-carboline scaffold, high HDAC6 inhibition potency with balanced physicochemical properties vivo studies. Compound 5d (repistat, IC50 = 6.32 nM) increased levels acetylated α-tubulin compared histone H3 ARPE-19 661W cells. promoted rescue atp6v0e1–/– zebrafish model photoreceptor dysfunction. A single intravitreal injection rd10 supported morphological functional preservation cells maintenance pigment epithelium array.
Язык: Английский
Процитировано
6
Stem Cell Reviews and Reports, Год журнала: 2024, Номер 20(6), С. 1459 - 1479
Опубликована: Май 29, 2024
Язык: Английский
Процитировано
4
Journal of Clinical Medicine, Год журнала: 2024, Номер 13(16), С. 4680 - 4680
Опубликована: Авг. 9, 2024
Background: Retinitis pigmentosa (RP) is a group of hereditary retinal dystrophies characterized by progressive degeneration photoreceptor cells, which results in debilitating visual impairment. This systematic review aims to evaluate the efficacy and safety emerging treatment modalities for RP, including gene therapy, mesenchymal-cell-based approaches, supplementary interventions. Methods: A comprehensive search electronic databases was conducted identify relevant studies published up February 2024. Studies reporting outcomes interventions randomized controlled trials, non-randomized studies, case series, were included. Data extraction synthesis performed according predefined criteria, focusing on assessing quality evidence summarizing key findings. Results: The yielded 13 meeting inclusion encompassing diverse study designs. Gene therapy emerged as promising therapeutic approach, with several favorable regarding function preservation disease stabilization. Mesenchymal-cell-based therapies also demonstrated potential benefits, although remains limited heterogeneous. Supplementary interventions, nutritional supplements neuroprotective agents, exhibited variable efficacy, conflicting findings across studies. Conclusions: Despite lack definitive curative treatments, promise slow progression preserve individuals RP. However, substantial gaps heterogeneity methodologies underscore need further research elucidate optimal strategies, refine patient selection enhance long-term outcomes. provides current highlights directions future advance care management
Язык: Английский
Процитировано
4
Molecular Therapy — Nucleic Acids, Год журнала: 2025, Номер 36(1), С. 102482 - 102482
Опубликована: Фев. 11, 2025
Inherited retinal dystrophies (IRDs), such as retinitis pigmentosa and Stargardt disease, are a group of rare diseases caused by mutations in more than 300 genes that currently have no treatment most cases. They commonly trigger blindness other ocular affectations due to cell degeneration. Gene editing has emerged promising powerful strategy for the development IRD therapies, allowing permanent correction pathogenic variants. Using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 transcription activator-like effector nucleases (TALEN) gene-editing tools, we precisely corrected seven hiPS lines derived from patients carrying ABCA4, BEST1, PDE6A, PDE6C, RHO, or USH2A. Homozygous point insertions/deletions resulted highest homology-directed repair efficiencies, with at least half clones repaired properly without off-target effects. Strikingly, heterozygous variant was achieved using wild-type allele patient template DNA repair. These results suggest unexpected potential application CRISPR donor template-free single-nucleotide modifications. Additionally, exhibited reversion disease-associated phenotype cellular models. data strengthen study gene editing-based approaches treatment.
Язык: Английский
Процитировано
0
Pathology - Research and Practice, Год журнала: 2023, Номер 248, С. 154619 - 154619
Опубликована: Июнь 13, 2023
Язык: Английский
Процитировано
6
International Journal of Ophthalmology, Год журнала: 2023, Номер 17(1), С. 188 - 200
Опубликована: Дек. 25, 2023
AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze advantages, limitations, possible solutions common to all tasks. METHODS: We searched three academic databases, including PubMed, Web Science, Ovid, date August 2022. matched screened according target keywords publication year retrieved a total 4358 research papers keywords, which 23 studies were on applying diagnosing images. RESULTS: Deep can detect various diseases achieve great performance, diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, detachment, other peripheral diseases. Compared images, scanning laser ophthalmoscopy enables capture ocular up 200° single exposure, observe more areas retina. CONCLUSION: The combination artificial intelligence will performance multiple future.
Язык: Английский
Процитировано
6
iScience, Год журнала: 2024, Номер 27(4), С. 109380 - 109380
Опубликована: Март 1, 2024
Highlights•Cone photoreceptor damage by light exposure stress is increased in Otud7b−/− mice•Otud7b deficiency exacerbates cone degeneration retinitis pigmentosa mouse model•NF-κB activated cells of the light-exposed retina•NF-κB inhibition attenuates retinaSummaryPrimary and secondary death retinal degenerative diseases, including age-related macular (AMD) (RP), leads to severe visual impairment blindness. Although protection diseases crucial for maintaining vision, underlying molecular mechanisms are unclear. Here, we found that deubiquitinase Otud7b/Cezanne predominantly expressed retina. We analyzed mice, which were subjected light-induced damage, a dry AMD model, or mated with an RP observed degeneration. Using RNA-sequencing bioinformatics analysis followed luciferase reporter assay, Otud7b downregulates NF-κB activity. Furthermore, attenuated retina stress-induced neuronal cell resulting from deficiency. Together, our findings suggest protects photoreceptors modulating activity.Graphical abstract
Язык: Английский
Процитировано
2
FEBS Journal, Год журнала: 2023, Номер 291(5), С. 986 - 1007
Опубликована: Дек. 1, 2023
Photoreceptor apoptosis is the main pathological feature of retinal degenerative diseases; however, underlying molecular mechanism has not been elucidated. Recent studies have shown that N‐myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on brain and spinal cord. In addition, our previous confirmed NDRG2 expressed in mouse photoreceptors counteracts N ‐methyl‐ ‐nitrosourea (MNU)‐induced apoptosis. However, remains unclear. this study, we observed expression was only significantly inhibited after MNU treatment but also hydrogen peroxide treatment, photoreceptor alleviated or aggravated overexpression knockdown 661W cell line, respectively. The inhibitor Z‐VAD‐FMK rescued induced by knockdown. Next, screened identified tissue metalloproteinases 3 (TIMP3) as molecule cells using quantitative real‐time polymerase chain reaction. TIMP3 inhibiting matrix (MMPs). Subsequently, found signal transducer activator transcription (STAT3) mediated NDRG2‐associated regulation TIMP3. Finally, overexpressed tissues intravitreally injecting an adeno‐associated virus with vivo . Results showed upregulated phospho‐STAT3 (p‐STAT3) TIMP3, while suppressing MNU‐induced MMP expression. Our findings revealed how regulates STAT3/TIMP3/MMP pathway uncovered its photoreceptors.
Язык: Английский
Процитировано
4