Article
Multidisciplinary Sciences
Dongju Won, Joo-Yeon Hwang, Yeeun Shim, Suk Ho Byeon, Junwon Lee, Christopher Seungkyu Lee, Min Kim, Hyun Taek Lim, Jong Rak Choi, Seung-Tae Lee, Jinu Han
Summary: MEIs are often missed due to exceeding read lengths of short-read sequencing technologies, but a grep search program was developed in this study to efficiently detect the RP1 Alu insertion. The Alu insertion in RP1 exon 4 was found to be a common founder mutation in Korean population.
SCIENTIFIC REPORTS
(2021)
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)
Article
Biochemistry & Molecular Biology
Christina Zeitz, Cecile Mejecase, Christelle Michiels, Christel Condroyer, Juliette Wohlschlegel, Marine Foussard, Aline Antonio, Vanessa Demontant, Lisa Emmenegger, Audrey Schalk, Marion Neuille, Elise Orhan, Sebastien Augustin, Crystel Bonnet, Amrit Estivalet, Frederic Blond, Steven Blanchard, Camille Andrieu, Sandra Chantot-Bastaraud, Thierry Leveillard, Saddek Mohand-Said, Jose-Alain Sahel, Isabelle Audo
Summary: This study identified a novel pathogenic gene defect linked to a relatively mild inherited retinal disorder. It also revealed the localization of a specific protein in the retina for the first time, implicating its association with mitochondrial dysfunction. The findings contribute to the understanding of the pathogenic mechanisms in non-syndromic inherited retinal disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Genetics & Heredity
Maria Solaguren-Beascoa, Kinga M. Bujakowska, Cecile Mejecase, Lisa Emmenegger, Elise Orhan, Marion Neuille, Saddek Mohand-Said, Christel Condroyer, Marie-Elise Lancelot, Christelle Michiels, Vanessa Demontant, Aline Antonio, Melanie Letexier, Jean-Paul Saraiva, Christine Lonjou, Wassila Carpentier, Thierry Leveillard, Eric A. Pierce, Helene Dollfus, Jose-Alain Sahel, Shomi S. Bhattacharya, Isabelle Audo, Christina Zeitz
Summary: Rod-cone dystrophy, characterized by rod and cone photoreceptor degeneration, is associated with mutations in over 65 genes. A homozygous variant in WDR34 was identified through homozygosity mapping and whole-exome sequencing in a case of autosomal recessive non-syndromic RCD, marking the first report of such association with WDR34 mutation.
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
Amithavikram R. Hathibelagal, Shrikant R. Bharadwaj, Subhadra Jalali, Ahalya Subramanian, John L. Barbur
Summary: A new method for assessing rod and cone sensitivity was studied, indicating that cone-specific deficits were larger than rod-specific deficits in cone-dominated diseases, while rod-specific deficits were larger than cone-specific deficits in rod-dominated disease. This suggests that this new testing method could be valuable in detecting specific rod/cone losses without the need for dark adaptation.
OPHTHALMIC AND PHYSIOLOGICAL OPTICS
(2021)
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
Genetics & Heredity
Jin Kyun Oh, Jose G. Vargas Del Valle, Jose Ronaldo Lima de Carvalho, Young Joo Sun, Sarah R. Levi, Joseph Ryu, Jing Yang, Takayuki Nagasaki, Andres Emanuelli, Nailyn Rasool, Rando Allikmets, Janet R. Sparrow, Natalio J. Izquierdo, Jacque L. Duncan, Vinit B. Mahajan, Stephen H. Tsang
Summary: This study describes the phenotypic findings in three unrelated patients with novel mutations in TTLL5, expanding the understanding of TTLL5-mediated retinal disease. The study suggests that mutations in TTLL5 may not only cause cone-rod and cone dystrophies, but also sectoral retinal dystrophy.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Neurosciences
Joseph Thomas Ortega, Tanu Parmar, Miguel Carmena-Bargueno, Horacio Perez-Sanchez, Beata Jastrzebska
Summary: This study demonstrates the pharmacological potential of quercetin in slowing down the progression of retinitis pigmentosa and mitigating the detrimental effects of the P23H Rho mutation. Quercetin improves stability and function of P23H Rho, as well as retinal morphology and function in mice. It also downregulates UPR signaling and oxidative stress markers.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Biology
Mei Nakahara, Akio Oishi, Manabu Miyata, Hanako Ohashi Ikeda, Tomoko Hasegawa, Shogo Numa, Yuki Otsuka, Maho Oishi, Fumihiko Matsuda, Akitaka Tsujikawa
Summary: Concentric retinitis pigmentosa is a rare form of RP with better visual function, preserved ellipsoid zones, and subnormal but recordable responses on electroretinogram. Genetic testing may reveal different causative genes in patients with this condition. Myotonic dystrophy-associated retinopathy is an important differential diagnosis to consider.
Article
Genetics & Heredity
Xiao-Ru Yang, Faazil Kassam, A. Micheil Innes
Summary: GNB1-related disorder is a condition characterized by intellectual disability, abnormal tone, and other variable neurological and systemic symptoms. The GNB1 gene encodes the beta 1 subunit of a G-protein complex involved in signal transduction. While rod-cone dystrophy has not been established as a common feature of this disorder in humans, a new case study reports its presence, expanding the phenotype and contributing to a better understanding of GNB1-related disorder.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Nina Kobal, Tjasa Krasovec, Maja Sustar, Marija Volk, Borut Peterlin, Marko Hawlina, Ana Fakin
Summary: Mutations in the rhodopsin gene (RHO) are a common cause of retinitis pigmentosa (RP) and congenital stationary night blindness (CSNB). A study screening 60 patients with mutation p.G90D revealed that 53.3% of patients developed RP, contrary to previous reports. The clinical characteristics did not show significant associations with family, sex, or age, except for cystoid macular edema being observed in only one family.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Enzo M. Vingolo, Lorenzo Casillo, Laura Contento, Francesca Toja, Antonio Florido
Summary: The study aimed to evaluate the relationship between circulating free radicals in blood and cystoid macular edema (CME) in Retinitis Pigmentosa (RP) patients. The results showed a significant increase in free oxygen radicals levels in RP patients with CME, suggesting that oxidative stress may accelerate cone cell damage.
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.
Review
Biochemistry & Molecular Biology
M. Y. Cynthia Stafford, Colin E. Willoughby, Colum P. Walsh, Declan J. McKenna
Summary: This systematic review and meta-analysis investigates the value of miR-21 expression as a prognostic measurement in prostate cancer (PCa) patients. The findings suggest that elevated levels of miR-21 are associated with poor prognosis in PCa patients, and miR-21 expression may be a useful prognostic biomarker in this disease.
BIOSCIENCE REPORTS
(2022)
Article
Ophthalmology
Mohit Parekh, Vito Romano, Kareem Hassanin, Valeria Testa, Rintra Wongvisavavit, Stefano Ferrari, Colin Willoughby, Diego Ponzin, Vishal Jhanji, Namrata Sharma, Julie Daniels, Stephen B. Kaye, Sajjad Ahmad, Hannah Levis
Summary: This study summarized the graft loading, transporting and delivery devices used for endothelial keratoplasty, highlighting the importance of new techniques and devices in improving clinical outcomes and reducing the learning curve.
CURRENT EYE RESEARCH
(2022)
Article
Virology
Connor G. G. Bamford, Lindsay Broadbent, Elihu Aranday-Cortes, Mary McCabe, James McKenna, David G. Courtney, Olivier Touzelet, Ahlam Ali, Grace Roberts, Guillermo Lopez Campos, David Simpson, Conall McCaughey, Derek Fairley, Ken Mills, Ultan F. Power
Summary: This study finds that the evolution of SARS-CoV-2 is restrained in pediatric respiratory epithelial cells but still exhibits significant genetic plasticity shaped by both viral and host cell factors.
Review
Ophthalmology
Neeru A. Vallabh, Stephnie Kennedy, Riccardo Vinciguerra, Keri McLean, Hannah Levis, Davide Borroni, Vito Romano, Colin E. Willoughby
Summary: The corneal endothelium plays a crucial role in maintaining a healthy cornea, but its loss can occur naturally with age and can be exacerbated by glaucoma and its treatments. This review explores the abnormalities observed in the corneal endothelium in different glaucoma phenotypes and evaluates the use of Descemet membrane endothelial keratoplasty (DMEK) in managing corneal endothelial failure for glaucoma patients.
JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Medicine, Research & Experimental
Marc Fuchs, Clara Radulescu, Miao Tang, Arun Mahesh, Deborah Lavin, Syed Umbreen, James McKenna, Mark Smyth, Eilis McColgan, Zoltan Molnar, Chris Baxter, Timofey Skvortsov, Aditi Singh, Fiona Rogan, Julia Miskelly, Stephen Bridgett, Derek Fairley, David A. Simpson
Summary: This study developed a miniaturized library preparation protocol called Mini-XT, which is more cost-effective for sequencing SARS-CoV-2 genomes. The protocol reduces library preparation reagent volumes and overall tip usage while maintaining sequencing quality. Validation through sequencing a large number of samples demonstrated that Mini-XT has comparable sequencing quality and lineage calling results to standard protocols.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Kandasamy Kathirvel, Lester Karen, Ravinarayanan Haribalaganesh, Ramasamy Krishnadas, Veerappan Muthukkaruppan, Brian Lane, David A. Simpson, Kasia Goljanek-Whysall, Carl Sheridan, Devarajan Bharanidharan, Colin E. Willoughby, Srinivasan Senthilkumari
Summary: This study investigates the temporal changes in gene expression in response to dexamethasone treatment in human trabecular meshwork cells, and identifies potential therapeutic targets for the management of glucocorticoid-induced ocular hypertension and glaucoma.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Francisco Cammarata-Scalisi, Michele Callea, Diego Martinelli, Colin Eric Willoughby, Antonio Cardenas Tadich, Maykol Araya Castillo, Maria Angelina Lacruz-Rengel, Marco Medina, Piercesare Grimaldi, Enrico Bertini, Julian Nevado
Summary: Phelan-McDermid syndrome is a rare and complex neurodevelopmental disorder caused by microdeletion or mutations in the SHANK3 gene on chromosome 22. The clinical presentation is variable, and diagnosis requires genetic analysis and multidisciplinary care.
Article
Genetics & Heredity
Michele Callea, Diego Martinelli, Francisco Cammarata-Scalisi, Chiara Grimaldi, Houweyda Jilani, Piercesare Grimaldi, Colin Eric Willoughby, Antonino Morabito
Summary: Dyskeratosis congenita is a genetic syndrome with diverse clinical manifestations, including bone marrow failure and tumors. This review discusses the clinical characteristics, molecular genetics, disease progression, treatment options, and differential diagnosis of the disease, providing personalized medical assessment and family genetic counseling.
Review
Ophthalmology
Lauren J. Coan, Bryan M. Williams, Venkatesh Krishna Adithya, Swati Upadhyaya, Ala Alkafri, Silvester Czanner, Rengaraj Venkatesh, Colin E. Willoughby, Srinivasan Kavitha, Gabriela Czanner
Summary: Glaucoma is a major cause of irreversible vision impairment globally, and early detection plays a crucial role in preventing further loss. The use of artificial intelligence for glaucoma assessment, specifically in segmenting fundus images, is being explored as a potential solution to subjective expert assessments. This comprehensive review evaluates the existing approaches and identifies future research directions.
SURVEY OF OPHTHALMOLOGY
(2023)
Article
Respiratory System
Yue Su, Johnatas Dutra Silva, Declan Doherty, David A. Simpson, Daniel J. Weiss, Sara Rolandsson-Enes, Daniel F. McAuley, Cecilia M. O'Kane, Derek P. Brazil, Anna D. Krasnodembskaya
Summary: This study found that MSC EVs have immunomodulatory effects in ARDS through the miR-181a-PTEN-pSTAT5-SOCS1 pathway.
Article
Cell Biology
Breedge Callaghan, Neeru A. Vallabh, Colin E. Willoughby
Summary: Glaucoma is a complex neurodegenerative disease that causes irreversible sight loss. Oxidative stress plays a significant role in the pathogenesis of glaucoma. Deuterated polyunsaturated fatty acids (D-PUFAs) have shown potential in reducing cytotoxic oxidative stress in glaucoma. This study found that Tenon's ocular fibroblasts from glaucoma patients have increased basal oxidative stress and that D-PUFAs can rescue lipid peroxidation in these cells.
MECHANISMS OF AGEING AND DEVELOPMENT
(2023)
Article
Cell Biology
Eszter Emri, Oisin Cappa, Caoimhe Kelly, Elod Kortvely, John Paul SanGiovanni, Brian S. S. McKay, Arthur A. A. Bergen, David A. A. Simpson, Imre Lengyel
Summary: This study used single-cell RNA sequencing to investigate the transcriptomic changes induced by zinc supplementation in human primary retinal pigment epithelial (RPE) cells. The results showed that zinc supplementation had a multitude of effects on the RPE transcriptome, including modulation of genes involved in pigmentation, complement regulation, mineralization, and cholesterol metabolism processes associated with age-related macular degeneration (AMD).
Editorial Material
Pediatrics
Francisco Cammarata-Scalisi, Colin Eric Willoughby, Vito Romano, Michele Callea
Article
Genetics & Heredity
Kandasamy Kathirvel, Xiaochen Fan, Ravinarayanan Haribalaganesh, Devarajan Bharanidharan, Rajendrababu Sharmila, Ramasamy Krishnadas, Veerappan Muthukkaruppan, Colin E. Willoughby, Srinivasan Senthilkumari
Summary: This study identified key miRNAs that affect the development of ocular hypertension/glaucoma by comparing GC-responsiveness in human HTM cells. The unique miRNA signature between GC-R and GC-NR HTM cells was revealed for the first time, suggesting the possibility of developing new molecular targets.
Article
Cell Biology
Lee Armstrong, Colin E. Willoughby, Declan J. Mckenna
Summary: This study investigated the association between miR-143-3p and EMT in prostate cancer. The findings showed that miR-143-3p expression was significantly decreased in prostate cancer cells and it was associated with the EMT-associated gene AKT1. Further analysis suggested that miR-143-3p may serve as a predictor of disease recurrence in prostate cancer, making it a potential diagnostic and prognostic biomarker.
