Article
Genetics & Heredity
Young Hoon Jung, Jay Jiyong Kwak, Kwangsic Joo, Hyuk Jun Lee, Kyu Hyung Park, Min Seok Kim, Eun Kyoung Lee, Suk Ho Byeon, Christopher Seungkyu Lee, Jinu Han, Junwon Lee, Chang Ki Yoon, Se Joon Woo
Summary: This study investigated the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). The study found that the generalized RP group had a higher rate of visual field impairment progression to late-stage RP compared to the sector RP group. Best-corrected visual acuity deterioration was observed only in the generalized RP group. The study also identified several RHO gene mutations, including some that presented with both generalized and sector RP phenotypes.
FRONTIERS IN GENETICS
(2023)
Review
Pharmacology & Pharmacy
Joseph Thomas Ortega, Beata Jastrzebska
Summary: The retina is a multilayer neuronal tissue at the back of the eye that transduces light into neural impulses. Many eye diseases lead to retina degeneration, with RP being a common hereditary disorder related to mutations in rhodopsin. In RP, sustained inflammation exacerbates due to abnormal genetic background, leading to photoreceptor decline.
Article
Multidisciplinary Sciences
Divya Ail, Diane Nava, In Pyo Hwang, Elena Brazhnikova, Celine Nouvel-Jaillard, Alexandre Dentel, Corentin Joffrois, Lionel Rousseau, Julie Degardin, Stephane Bertin, Jose-Alain Sahel, Olivier Goureau, Serge Picaud, Deniz Dalkara
Summary: To test novel therapies, suitable nonhuman primate models are needed, but there is a lack of relevant macaque models of retinal degeneration. Researchers have generated three distinct inducible cynomolgus macaque models of retinal degeneration to address this issue. Among the three models, the CRISPR-Cas9-based approach is the most advantageous for recapitulating disease-specific features and ease of implementation. The acute model, on the other hand, degenerates the fastest and is the most relevant for testing end-stage vision restoration therapies.
Article
Genetics & Heredity
Brian G. Ballios, Emily M. Place, Luis Martinez-Velazquez, Eric A. Pierce, Jason I. Comander, Rachel M. Huckfeldt
Summary: Sector and pericentral forms of hereditary retinitis pigmentosa are rare, and studies suggest that they may have distinct disease spectra. Analysis of a specific genotype revealed a wide phenotypic range in patients, with significant intrafamilial variability in phenotype. Long-term follow-up showed good prognosis for central visual acuity in the absence of macular disease, but disease progression over extended periods was observed.
Article
Ophthalmology
Wei Liu, Ruru Guo, Huijie Hao, Jian Ji
Summary: A novel heterozygous nonsense mutation of RHO gene was identified in a Chinese family with retinitis pigmentosa through targeted region sequencing. Bioinformatics analysis indicated that the mutation is pathogenic, expanding the spectrum of RHO gene mutations and enriching the phenotype-genotype correlation of retinitis pigmentosa.
Article
Ophthalmology
Xuan-Thanh-An Nguyen, Mays Talib, Caroline van Cauwenbergh, Mary J. van Schooneveld, Marta Fiocco, Jan Wijnholds, Jacoline B. Ten Brink, Ralph J. Florijn, Nicoline E. Schalij-Delfos, Gislin Dagnelie, Maria M. van Genderen, Elfride de Baere, Magda A. Meester-Smoor, Julie De Zaeytijd, Irina Balikova, Alberta A. Thiadens, Carel B. Hoyng, Caroline C. Klaver, L. Ingeborgh van den Born, Arthur A. Bergen, Bart P. Leroy, Camiel J. F. Boon
Summary: By reviewing medical charts of 100 patients with autosomal dominant RHO-associated RP, the study found significant differences in disease progression between patients with generalized RP phenotype and those with sector RP phenotype in terms of central visual field, suggesting that the optimal window for intervention should be before the 5th decade of life. The study also suggests that the PR + RPE complex could be a potential surrogate endpoint for BCVA in future studies.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Tongdan Zou, Ting Wang, Fangyuan Zhen, Xu He, Shuqian Dong, Houbin Zhang
Summary: Exogenous expression of PDE5 prevents photoreceptor degeneration and promotes outer segment development in RD1 mice. Unlike the photoreceptor-specific PDE6, PDE5 shows different distribution and expression patterns. Lowering cGMP levels in photoreceptors rescues photoreceptors in RD1 retinas.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Yoko Ozawa, Eriko Toda, Kohei Homma, Hideto Osada, Norihiro Nagai, Kazuo Tsubota, Hideyuki Okano
Summary: In this study, the researchers demonstrated that 4-phenylbutyric acid (PBA) can protect photoreceptor function and prevent death in a hereditary blinding disease called retinitis pigmentosa (RP). They found that constant PBA treatment preserved a greater number of photoreceptors and upregulated key mitochondrial regulators, leading to improved mitochondrial function. This protection was also achieved through epigenetic changes. These findings provide evidence for the potential use of PBA as a treatment for RP and highlight its neuroprotective effects.
Article
Medicine, Research & Experimental
Wei Du, Jiarui Li, Xin Tang, Wenzhen Yu, Mingwei Zhao
Summary: In this study, a CRISPR/SaCas9-mediated gene reduction system was developed to inactivate Rho gene mutation and replace normal rhodopsin in a specific mouse model, leading to improved retinal function. These findings suggest that CRISPR/SaCas9-based reduction and replacement gene therapy could potentially offer therapeutic benefits for Rho mutant ADRP.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Genetics & Heredity
Maria Kaukonen, Michelle E. McClements, Robert E. MacLaren
Summary: Retinitis pigmentosa (RP) is a common inherited retinal degenerative disease, and pathogenic variants in the Rhodopsin (RHO) gene are the main cause of autosomal dominant RP (adRP). Base editing technology provides exciting possibilities for treating adRP, but further research is needed for optimization.
Article
Ophthalmology
Xiaozhen Liu, Ruixuan Jia, Xiang Meng, Ying Li, Liping Yang
Summary: Studies on treating adRP using CRISPR/Cas9 targeting RHO show potential therapeutic effects, but the development of humanized mouse models is still in its early stages.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Ophthalmology
Dawiyat Massoudi, Sean Gorman, Yien-Ming Kuo, Takao Iwawaki, Scott A. Oakes, Feroz R. Papa, Douglas B. Gould
Summary: This study evaluated the contribution of IRE1a to photoreceptor development, homeostasis, and degeneration. The results suggest that IRE1a is dispensable for photoreceptor development but important for photoreceptor homeostasis in aging retinas and for protecting against ER stress-mediated photoreceptor degeneration.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Review
Neurosciences
Fangyuan Zhen, Tongdan Zou, Ting Wang, Yongwei Zhou, Shuqian Dong, Houbin Zhang
Summary: Rhodopsin is a light-sensitive receptor that initiates the phototransduction cascade. Mutations in the rhodopsin-encoding gene are the leading cause of retinitis pigmentosa. The high allelic heterogeneity suggests complex pathogenic mechanisms related to protein misfolding and dysfunction.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Chemistry, Medicinal
Francesca Picarazzi, Marika Zuanon, Gaia Pasqualetto, Silvia Cammarone, Isabella Romeo, Mark T. Young, Andrea Brancale, Marcella Bassetto, Mattia Mori
Summary: A computational-boosted workflow was used to select potential chaperones for P23H opsins using homology modeling, molecular dynamics simulations, and virtual screening. In vitro studies confirmed the reliability of the generated structural model and identified new chemotypes of safe and effective chaperones that can enhance P23H opsin trafficking to the outer cell membrane.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Multidisciplinary Sciences
Ammanie Abdul-Fatah, Leila Esmaeilisaraji, Crisel Mae Juan, Martin Holcik
Summary: This paper provides support for the creation of a mitochondrial disease patient registry in Canada through a systematic scoping review. It also fills a knowledge gap by providing a narrative synthesis of published literature on these registries.