Article
Genetics & Heredity
Akio Oishi, Kaoru Fujinami, Go Mawatari, Nobuhisa Naoi, Yasuhiro Ikeda, Shinji Ueno, Kazuki Kuniyoshi, Takaaki Hayashi, Hiroyuki Kondo, Atsushi Mizota, Kei Shinoda, Sentaro Kusuhara, Makoto Nakamura, Takeshi Iwata, Akitaka Tsujikawa, Kazushige Tsunoda
Summary: This study reported 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy and identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort, showcasing different phenotypes and ages of onset.
Article
Cell Biology
Maria Jose Ruiz-Pastor, Xavier Sanchez-Saez, Oksana Kutsyr, Henar Albertos-Arranz, Carla Sanchez-Castillo, Isabel Ortuno-Lizaran, Natalia Martinez-Gil, Lorena Vidal-Gil, Lucia Mendez, Manuel Sanchez-Martin, Victoria Maneu, Pedro Lax, Nicolas Cuenca
Summary: This study successfully generated and characterized a mouse model carrying the p.Arg195Leu mutation, which simulates the retinal degeneration characteristic of central areolar choroidal dystrophy. The generated mouse models can be used to study the mechanisms involved in the onset and progression of the disease, as well as to test the efficacy of new therapeutic strategies.
CELL DEATH & DISEASE
(2023)
Article
Clinical Neurology
Emrah Gumusgoz, Sahba Kasiri, Dikran R. Guisso, Jun Wu, Matthew Dear, Brandy Verhalen, Berge A. Minassian
Summary: Adult polyglucosan body disease (APBD) and Lafora disease (LD) are two autosomal recessive neurological disorders caused by gene mutations. Both diseases share a common pathology of abnormal glycogen accumulation. By reducing the expression of glycogen synthase, we were able to decrease the formation of pathological polyglucosan bodies and improve early neuroinflammatory markers of disease. This study provides proof of principle for a lifelong treatment for APBD and LD, and may be applicable to other glycogen storage diseases.
Article
Medicine, General & Internal
Giulio Antonelli, Mariacristina Parravano, Lucilla Barbano, Eliana Costanzo, Matteo Bertelli, Maria Chiara Medori, Vincenzo Parisi, Lucia Ziccardi
Summary: PRPH2 gene mutations are frequently found in inherited retinal dystrophies (IRD) and cause a wide range of clinical phenotypes. In this study, 28 subjects with IRD carrying pathogenic PRPH2 mutations were analyzed. The results showed that these patients presented with reduced visual acuity and abnormal dark adaptation in their 40s. Various imaging methods, such as fundus autofluorescence and optical coherence tomography angiography, were found to be effective in the early recognition and detection of this dystrophy.
Article
Neurosciences
Tal Brandwine, Reut Ifrah, Tzofia Bialistoky, Rachel Zaguri, Elisheva Rhodes-Mordov, Liliana Mizrahi-Meissonnier, Dror Sharon, Vladimir L. Katanaev, Offer Gerlitz, Baruch Minke
Summary: DHDDS is a widely expressed enzyme that is highly conserved in various tissues and animal species. Using the Drosophila model, it has been shown that compromising DHDDS in developing retina can result in a unique pattern of retinal degeneration. This study suggests that DHDDS is essential for normal retinal formation.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Chemistry, Medicinal
Song Zhang, Zhujun Cheng, Yanan Wang, Tianyu Han
Summary: The progress of miRNA drugs in clinical trials is slow due to the characteristic of targeting multiple genes, leading to inevitable adverse effects.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Plant Sciences
Yan Yan
Summary: This review assesses recent progress in the identification of new mobile sRNAs, discussing their functions in coordinating developmental, physiological, and defense-related processes in plants. The forms of mobile sRNAs and their trafficking mechanisms are also discussed. The authors highlight the importance of this field for future research.
Article
Genetics & Heredity
Jana Zernant, Winston Lee, Jun Wang, Kerry Goetz, Ehsan Ullah, Takayuki Nagasaki, Pei-Yin Su, Gerald A. Fishman, Stephen H. Tsang, Santa J. Tumminia, Brian P. Brooks, Robert B. Hufnagel, Rui Chen, Rando Allikmets
Summary: Variants in the ABCA4 locus cause phenotypic heterogeneity, and some of the complexity is likely explained by trans-modifiers in unlinked loci. This study identified significant enrichment of variants in the ROM1 and PRPH2 genes in patients with ABCA4 disease. The associations were replicated in an independent cohort, indicating the importance of rare and common variants in these two unlinked loci in modulating the penetrance of ABCA4 disease.
Article
Biochemistry & Molecular Biology
Larissa Ikelle, Mustafa Makia, Tylor Lewis, Ryan Crane, Mashal Kakakhel, Shannon M. Conley, James R. Birtley, Vadim Y. Arshavsky, Muayyad R. Al-Ubaidi, Muna I. Naash
Summary: Mutations in the PRPH2 gene can lead to retinal degeneration. Contrary to previous understanding, new research reveals that these mutations affect PRPH2 function by interfering with oligomerization, resulting in highly affected rod cells and less affected cone cells. This finding is important for the development of therapeutic approaches for PRPH2-associated diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lars Tebbe, Haarthi Sakthivel, Mustafa S. Makia, Mashal Kakakhel, Shannon M. Conley, Muayyad R. Al-Ubaidi, Muna Naash
Summary: Prph2, a photoreceptor-specific protein, is essential for the structure and function of photoreceptor outer segments. Mutations in PRPH2 can lead to various retinal diseases, including degeneration of photoreceptors and defects in neighboring tissues such as the RPE. Research shows that these mutations also cause structural and functional abnormalities in the RPE, which can vary in severity and contribute to the clinical phenotype observed in patients.
Editorial Material
Biochemistry & Molecular Biology
Huiya Yang, Robert H. Brown, Dan Wang, Kevin A. Strauss, Guangping Gao
Summary: De novo glycosphingolipid (GSL) biosynthesis defects cause severe neurological diseases with no effective treatment currently available. Recombinant adeno-associated virus (AAV)-mediated gene therapy has emerged as a promising treatment for monogenic diseases and may be particularly suitable for these neurological conditions.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Sweta Khanal, Beatriz Schueng Zancanela, Jacob Oche Peter, Alex Sutton Flynt
Summary: This study provides a comprehensive analysis of small RNAs in annelids, revealing a large number of microRNAs and piRNAs. The study also identifies the expression patterns and pathway composition of miRNAs and piRNAs related to animal development and metamorphosis. Additionally, the study finds that the configuration of RNAi factors in annelids is similar to that of other annelids and mollusks, suggesting the presence of similar biology in a wider clade.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Agronomy
Farzad Bidari, Yaghoub Fathipour, Sassan Asgari, Mohammad Mehrabadi
Summary: This study characterized and analyzed the expression of miRNA core genes in B. tabaci and investigated the impact of their silencing on the insect's fitness. The results showed that silencing the miRNA core genes reduced miRNA levels and affected the fertility and survival of B. tabaci. The miRNA core genes could serve as attractive targets for developing an RNAi-based strategy against this insect pest.
PEST MANAGEMENT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Chen Zhu, Jia-Hui Liu, Jian-Hua Zhao, Ting Liu, Yun-Ya Chen, Chun-Han Wang, Zhong-Hui Zhang, Hui-Shan Guo, Cheng-Guo Duan
Summary: A study has found that the fungal pathogen Verticillium dahliae counters cross-kingdom antifungal RNA interference (RNAi) by secreting a protein called VdSSR1. This protein suppresses the movement of small RNAs (sRNAs) between the host plant and the fungus, increasing the virulence of the fungus in plants.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Fisheries
Thaneeya Nantapojd, Sakol Panyim, Chalermporn Ongvarrasopone
Summary: The study found that wsv-miR-9 plays an important role in early viral gene expression, leading to a delay in viral replication when its expression is inhibited. This highlights the potential for wsv-miR-9 as a target for controlling WSSV infection in shrimp.
Article
Ophthalmology
Errol W. Chan, Elizabeth Yang, Mohab Eldeeb, James W. Bainbridge, Lyndon Cruz, Paul S. Sullivan, Mahi M. Muqit, David G. Charteris, Miriam Minihan, Eric Ezra, Louisa Wickham
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2020)
Review
Ophthalmology
Thales Antonio Cabral de Guimaraes, Michalis Georgiou, James W. B. Bainbridge, Michel Michaelides
Summary: Age-related macular degeneration is a leading cause of irreversible blindness, and antivascular endothelial growth factor therapy has improved the management of neovascular AMD. Gene therapy approaches show promise in addressing challenges, but there are still controversies and safety concerns.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Cell Biology
Matthew J. Annear, Freya M. Mowat, Laurence M. Occelli, Alexander J. Smith, Paul G. Curran, James W. Bainbridge, Robin R. Ali, Simon M. Petersen-Jones
Summary: The Rpe65-deficient dog model has been crucial for studying LCA2 translational therapies. This study provided a comprehensive report on the natural history of retinal changes in this model, showing age-related decline in retinal sensitivity and thickness. The findings suggest that photoreceptor loss leads to vision impairment, but some desensitized photoreceptors may still exist in older dogs.
Article
Hematology
Giulia De Rossi, Maria Vahatupa, Enrico Cristante, Samantha Arokiasamy, Sidath E. Liyanage, Ulrike May, Laura Pellinen, Hannele Uusitalo-Jarvinen, James W. Bainbridge, Tero A. H. Jarvinen, James R. Whiteford
Summary: This study establishes the crucial role of SDC4 in pathological angiogenesis, particularly in eye diseases and tumor development. SDC4 is identified as a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization, representing a potential target for antiangiogenic therapies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cell Biology
Qitao Zhang, Feriel Presswalla, Robin R. Ali, David N. Zacks, Debra A. Thompson, Jason M. L. Miller
Summary: The autophagy inducer FLBZ shows promise as a potential therapeutic approach for dry AMD by increasing RPE autophagy flux, reducing lipid deposits, and promoting the production of energy sources.
Article
Cell Biology
Joana Ribeiro, Christopher A. Procyk, Emma L. West, Michelle O'Hara-Wright, Monica F. Martins, Majid Moshtagh Khorasani, Aura Hare, Mark Basche, Milan Fernando, Debbie Goh, Neeraj Jumbo, Matteo Rizzi, Kate Powell, Menahil Tariq, Michel Michaelides, James W. B. Bainbridge, Alexander J. Smith, Rachael A. Pearson, Anai Gonzalez-Cordero, Robin R. Ali
Summary: The research demonstrates restoration of visual function by transplanting purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration, resulting in complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals.
Article
Neurosciences
Claire Hippert, Anna B. Graca, Mark Basche, Aikaterini A. Kalargyrou, Anastasios Georgiadis, Joana Ribeiro, Ayako Matsuyama, Nozie Aghaizu, James W. Bainbridge, Alexander J. Smith, Robin R. Ali, Rachael A. Pearson
Summary: Gliosis is a complex process involving upregulation of IF proteins, changes in glial morphology, and increased deposition of inhibitory ECM molecules. Through RNAi approaches, it was found that GFAP and vimentin play crucial roles in the establishment of glial hypertrophy during disease progression. Suppression of both proteins led to severe changes in the retina's cytoarchitecture, suggesting potential therapeutic implications for modulating scar formation.
Article
Cell Biology
Ceniz Zihni, Anastasios Georgiadis, Conor M. Ramsden, Elena Sanchez-Heras, Alexis J. Haas, Britta Nommiste, Olha Semenyuk, James W. B. Bainbridge, Peter J. Coffey, Alexander J. Smith, Robin R. Ali, Maria S. Balda, Karl Matter
Summary: This study identifies a Cdc42-based dual effector signaling mechanism that drives actomyosin remodeling and, thereby, internalization of phagocytic ligands in retinal pigment epithelial cells.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Pathology
Enrico Cristante, Sidath E. Liyanage, Alexander J. Smith, Robin R. Ali, James W. B. Bainbridge
Summary: The study reveals that HIF1a promotes RPE degeneration and choroidal neovascularization in CreTrp1 mice, while HIF2a has a protective effect.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Review
Medicine, General & Internal
Mahiul M. K. Muqit, Manjit Mehat, Catey Bunce, James W. Bainbridge
Summary: This study aimed to assess the potential role of combined pars plana vitrectomy and intravitreal antibiotics in the acute management of exogenous endophthalmitis. A randomized controlled trial was conducted, and the results showed no significant difference in visual acuity between the two treatment groups at three and six months of follow-up. There was also no clear evidence of a difference in the need for additional surgical procedures.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2022)
Meeting Abstract
Ophthalmology
Michel Michaelides, Jialin Xu, Dai Wang, Peggy Wong, Albert Fung, Alexandra Forbes, Stuart Naylor, Robert Zeldin, Maria A. Parker, Richard Weleber, Thales Antonio Cabral de Guimaraes, Cagri Besirli, Yesa Yang, James Bainbridge
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
Olivia Jane Cundy, Ameenat Lola Solebo, Clemens Lange, Catey Bunce, James Bainbridge
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Review
Medicine, General & Internal
Ammar M. Yusuf, Mukhtar Bizrah, Catey Bunce, James W. Bainbridge
Summary: This study included one RCT on 53 patients with epiretinal membrane, finding that the immediate surgery group had slightly higher visual acuity at 12 months compared to the deferred surgery group. The effects of immediate surgery on visual acuity gains of 0.3 logMAR or more were uncertain, but at 12 months, no participants experienced a loss of visual acuity exceeding 0.3 logMAR.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)