Review
Genetics & Heredity
Wenhua Duan, Taicheng Zhou, Huawei Jiang, Minhui Zhang, Min Hu, Liwei Zhang
Summary: This study identified a novel variant in the CRB1 gene in a Chinese family with LCA, expanding the spectrum of CRB1 variants causing LCA.
BMC MEDICAL GENOMICS
(2022)
Article
Multidisciplinary Sciences
Samuel G. Jacobson, Artur Cideciyan, Allen C. Ho, Igor Peshenko, Alexandra Garafalo, Alejandro J. Roman, Alexander Sumaroka, Vivian Wu, Arun K. Krishnan, Rebecca Sheplock, Sanford L. Boye, Alexander M. Dizhoor, Shannon E. Boye
Summary: The ongoing first-in-human clinical trial of gene therapy for Leber congenital amaurosis due to mutations in the GUCY2D gene has shown promising early results, demonstrating safety and efficacy in both rod and cone photoreceptor function.
Article
Genetics & Heredity
Isabelle Perrault, Sylvain Hanein, Xavier Gerard, Nelson Mounguengue, Ryme Bouyakoub, Mohammed Zarhrate, Cecile Fourrage, Fabienne Jabot-Hanin, Beatrice Bocquet, Isabelle Meunier, Xavier Zanlonghi, Josseline Kaplan, Jean-Michel Rozet
Summary: This study investigates the non-coding regions of a non-syndromic LCA gene, identifying the most frequent disease allele.
Article
Genetics & Heredity
Amani Albakri, Phattrawan Pisuchpen, Jenina E. Capasso, Adele Schneider, Sarina Kopinsky, Tom Glaser, John P. -W. Chiang, Anamaria Akapito Yomai, Donna McNear, Alex V. Levin
Summary: The purpose of this article is to determine the cause of Leber congenital amaurosis (LCA) in Chuuk state, Federated States of Micronesia (FSM). Five patients with early-onset vision loss were examined in Chuuk state, FSM, and were initially misdiagnosed with microphthalmia. However, a complete ophthalmological exam established a clinical diagnosis of LCA. DNA sequencing revealed a homozygous CRB1 NM_201253.3:c.3134del pathogenic variant in affected individuals. This discovery of a founder pathogenic variant in CRB1 will lead to appropriate recurrence risk counseling.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Ophthalmology
Xufeng Dai, Xumin Jin, Qian Ye, Haixiao Huang, Lan Duo, Chunjie Lu, Jinhua Bao, Hao Chen
Summary: High expression of the RPE-specific RPE65 enzyme is crucial for generating 11-cis-retinal, a key component for vision. Deficiency in RPE65 can lead to severe retinal dysfunction, but early treatment with 11-cis-retinal in a mouse model shows promise in delaying cone degeneration and preserving retinal function.
EXPERIMENTAL EYE RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Wei Chiu, Ting-Yi Lin, Yun-Chia Chang, Henkie Isahwan-Ahmad Mulyadi Lai, Shen-Che Lin, Chun Ma, Aliaksandr A. Yarmishyn, Shiuan-Chen Lin, Kao-Jung Chang, Yu-Bai Chou, Chih-Chien Hsu, Tai-Chi Lin, Shih-Jen Chen, Yueh Chien, Yi-Ping Yang, De-Kuang Hwang
Summary: Inherited retinal dystrophies (IRDs) are rare eye diseases caused by gene mutations, and gene therapy has shown promising prospects in treating these diseases. Gene therapy for patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) has been approved by the FDA, marking a significant advancement in the field of genetic treatments for eye diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Anatomy & Morphology
Ankur Nahar, Seo-Hee Cho
Summary: Mutations in the CRB1 gene cause rare retinal diseases like RP12 and LCA8. While several mouse models have been proposed for RP12, few replicate the full spectrum of human LCA8 pathology. LCA8 is a unique type of retinal dystrophy driven by dysfunctional retinal progenitor cells, while other LCA subtypes and RP12 are caused by photoreceptor defects. Therefore, the most accurate LCA8-like mouse model should target both Crb1 and Crb2 genes in the early stages of eye development.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Yukari Takeda, Kazuma Sato, Yukari Hosoki, Shuji Tachibanaki, Chieko Koike, Akira Amano
Summary: This study investigates the divergent regulation of photoresponses in rods and cones. A detailed mathematical model based on the Hamer model was developed to analyze the differences in light sensitivity and desensitization between the two types of photoreceptor cells. The model successfully reconstructed the changes in concentrations of phosphorylated visual pigments, activated transducins, and phosphodiesterases in response to light intensity, ATP, and GTP.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Ditta Zobor, Britta Bruehwiler, Eberhart Zrenner, Nicole Weisschuh, Susanne Kohl
Summary: This study investigates the spectrum of LCA-associated genes in a large German cohort, providing valuable insights into the genetic and phenotypic diversity of LCA. The results indicate the importance of genetic information in gene therapeutic trials for LCA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Sriee Viswarubhiny, Rupa Anjanamurthy, Ayyasamy Vanniarajan, Devarajan Bharanidharan, Vijayalakshmi Perumalsamy, Periasamy Sundaresan
Summary: This study identified causative mutations in nine LCA patients through clinical exome sequencing, reporting novel mutations in PRPH2, CEP290, and ALMS1 in the Indian population, and observed a novel association of LCA phenotype with Jeune syndrome.
Article
Genetics & Heredity
Shijing Wu, Zhisheng Yuan, Zixi Sun, Fengxia Yao, Ruifang Sui
Summary: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder caused by a defective SLC19A2 gene, with characteristic triad manifestations of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Ophthalmic features such as retinitis pigmentosa and optic atrophy can also be present. This case illustrates that Leber congenital amaurosis may precede systemic manifestations in TRMA patients.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Maximilian J. Gerhardt, Claudia S. Priglinger, Guenther Rudolph, Karsten Hufendiek, Carsten Framme, Herbert Jaegle, Daniel J. Salchow, Andreas Anschuetz, Stylianos Michalakis, Siegfried G. Priglinger
Summary: This study presented the follow-up of the youngest treated patients in Germany with Leber congenital amaurosis caused by mutations in the RPE65 gene. The results showed significant improvement in vision and electrophysiological recovery in some patients after treatment with voretigene neparvovec gene therapy. These findings highlight the positive role of voretigene neparvovec in treating this devastating eye disease.
Article
Cardiac & Cardiovascular Systems
Mitsushige Murata, Takashi Kawakami, Masaharu Kataoka, Hidenori Moriyama, Takahiro Hiraide, Mai Kimura, Jin Endo, Takashi Kohno, Yuji Itabashi, Keiichi Fukuda
Summary: This study demonstrated that riociguat can improve cardiovascular conditions in patients with pulmonary hypertension, including enhancing cardiac output and right ventricular function. Echocardiography showed that riociguat can improve right ventricular structure and function in patients with varying degrees of pulmonary hypertension.
Article
Cardiac & Cardiovascular Systems
Javier Inserte, Jose A. Barrabes, David Aluja, Imanol Otaegui, Jordi Baneras, Laura Castellote, Ana Sanchez, Jose F. Rodriguez-Palomares, Victor Pineda, Elisabet Miro-Casas, Laia Mila, Rosa-Maria Lidon, Antonia Sambola, Filipa Valente, Agnes Rafecas, Marisol Ruiz-Meana, Antonio Rodriguez-Sinovas, Begona Benito, Irene Buera, Sara Delgado-Tomas, David Beneitez, Ignacio Ferreira-Gonzalez
Summary: Iron deficiency is associated with adverse left ventricular remodeling and larger infarct size in patients with anterior ST-segment elevation myocardial infarction. Studies in mice show that an iron deficiency diet reduces the activity of the endothelial nitric oxide synthase pathway, leading to oxidative stress and increased infarct size. Iron supplementation or sGC activators can prevent the negative effects of iron deficiency in mice.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2021)
Article
Ophthalmology
M. Dominik Fischer, Francesco Patalano, Christel Naujoks, Judit Banhazi, Christine Bouchet, Paul O'Brien, Christine Kay, Jane Green, Todd Durham, Helena Bradley, Nicola Williamson, Melissa Barclay, Joel Sims, Isabelle Audo
Summary: This study explores the psychometric properties of the ViSIO-PRO and ViSIO-ObsRO instruments in RP/LCA. The findings suggest that the questionnaires are reliable and valid measures in RP/LCA, and further research is needed to examine their responsiveness and interpretation of change scores.
OPHTHALMOLOGY AND THERAPY
(2023)
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
Multidisciplinary Sciences
A. Matsuyama, A. A. Kalargyrou, A. J. Smith, R. R. Ali, R. A. Pearson
Summary: The expression patterns of Chondroitin Sulphate Proteoglycans (CSPGs) in retinal degeneration are not well understood, but are recognized to play a crucial role in neuronal regrowth and regeneration. This study provides a comprehensive atlas of the expression patterns of individual CSPGs in different models of retinal degeneration, revealing significant heterogeneity in their expression. The findings suggest that better understanding the distribution of individual CSPGs can contribute to creating a more permissive microenvironment for neuro-regeneration and repair.
SCIENTIFIC REPORTS
(2022)
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)
Article
Biochemical Research Methods
Nozie D. Aghaizu, Katherine M. Warre-Cornish, Martha R. Robinson, Robin R. Ali, Rachael A. Pearson
Summary: This protocol outlines tracking retinal cell motility in live explanted mouse retinae, applicable to any fluorescently labeled cell, with careful tissue handling and further guidance for semi-automated data processing. For detailed usage and execution, refer to Aghaizu et al. (2021).
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)