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
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)
Article
Pharmacology & Pharmacy
Masashi Tawa, Takashi Shimosato, Keisuke Nakagawa, Tomio Okamura, Mamoru Ohkita
Summary: This study found that renovascular hypertension did not affect the vasorelaxant responses mediated by NO-sensitive and NO-insensitive forms of sGC, suggesting that sGC may not be responsible for the reduced NO bioavailability observed during renovascular hypertension.
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)
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
Ophthalmology
Yuki Kanzaki, Hirofumi Fujita, Keita Sato, Mio Hosokawa, Hiroshi Matsumae, Yuki Morizane, Hideyo Ohuchi
Summary: This study investigated the mechanisms of morphological abnormalities in a Leber congenital amaurosis 16 (LCA16) cell model and found that the absence of the Kir.7.1 potassium channel makes human retinal pigment epithelial (RPE) cells vulnerable to oxidative stress and ultimately results in cell death and morphological abnormalities.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Endocrinology & Metabolism
Yazeid Alhaidan, Henrik Thybo Christesen, Elena Lundberg, Mohammed A. Al Balwi, Klaus Brusgaard
Summary: This study identified a novel candidate gene, ADCY7, to cause CHI via activation of the GSIS pathway.
FRONTIERS IN ENDOCRINOLOGY
(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)
Article
Biochemistry & Molecular Biology
Pedro R. L. Perdigao, Bethany Ollington, Hali Sai, Amy Leung, Almudena Sacristan-Reviriego, Jacqueline van der Spuy
Summary: Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is involved in the assembly of phosphodiesterase 6 (PDE6) in photoreceptors, and genetic variations in AIPL1 cause Leber congenital amaurosis (LCA4) which leads to vision loss. Generating patient-derived LCA4 models for studying AIPL1 mutations may have limitations, therefore, a CRISPR/Cas9 approach was used to create an induced pluripotent stem cell line with a frameshift mutation in AIPL1. This model showed dysregulation of the phototransduction cascade, providing a novel platform for studying AIPL1 silencing and potential therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Multidisciplinary Sciences
Elliot H. Choi, Susie Suh, Andrzej T. Foik, Henri Leinonen, Gregory A. Newby, Xin D. Gao, Samagya Banskota, Thanh Hoang, Samuel W. Du, Zhiqian Dong, Aditya Raguram, Sajeev Kohli, Seth Blackshaw, David C. Lyon, David R. Liu, Krzysztof Palczewski
Summary: The study demonstrates that in vivo base editing can prolong the survival of cone photoreceptors and restore their function in a mouse model of Leber congenital amaurosis.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Kaitlyn R. Calabro, Sanford L. Boye, Shreyasi Choudhury, Diego Fajardo, James J. Peterson, Wei Li, Sean M. Crosson, Mi-Jung Kim, Dalian Ding, Richard Salvi, Shinichi Someya, Shannon E. Boye
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Neurosciences
Marshall S. Goodwin, Cara L. Croft, Hunter S. Futch, Daniel Ryu, Carolina Ceballos-Diaz, Xuefei Liu, Giavanna Paterno, Catalina Mejia, Doris Deng, Kimberly Menezes, Laura Londono, Kefren Arjona, Mary Parianos, Van Truong, Eva Rostonics, Amanda Hernandez, Sanford L. Boye, Shannon E. Boye, Yona Levites, Pedro E. Cruz, Todd E. Golde
MOLECULAR NEURODEGENERATION
(2020)
Review
Ophthalmology
Alexandra Garafalo, Artur Cideciyan, Elise Heon, Rebecca Sheplock, Alexander Pearson, Caberry WeiYang Yu, Alexander Sumaroka, Gustavo D. Aguirre, Samuel G. Jacobson
PROGRESS IN RETINAL AND EYE RESEARCH
(2020)
Article
Biotechnology & Applied Microbiology
Hyung-Joo Kwon, Keyun Qing, Selvarangan Ponnazhagan, Xu-Shan Wang, David M. Markusic, Siddhant Gupte, Shannon E. Boye, Arun Srivastava
HUMAN GENE THERAPY
(2020)
Article
Biotechnology & Applied Microbiology
Sanford L. Boye, Shreyasi Choudhury, Sean Crosson, Giovanni Di Pasquale, Sandra Afione, Russell Mellen, Victoria Makal, Kaitlyn R. Calabro, Diego Fajardo, James Peterson, Hangning Zhang, Matthew T. Leahy, Colin K. Jennings, John A. Chiorini, Ryan F. Boyd, Shannon E. Boye
Article
Behavioral Sciences
Joel D. Mainland, Linda A. Barlow, Steven D. Munger, Sarah E. Millar, M. Natalia Vergara, Peihua Jiang, James E. Schwob, Bradley J. Goldstein, Shannon E. Boye, Jeffrey R. Martens, Donald A. Leopold, Linda M. Bartoshuk, Richard L. Doty, Thomas Hummel, Jayant M. Pinto, Casey Trimmer, Christine Kelly, Edmund A. Pribitkin, Danielle R. Reed
Article
Biochemistry & Molecular Biology
Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon
Summary: The study evaluated two intracranially administered adeno-associated virus serotype 8 variants for potential treatment of MPS IIIB, with one variant (double Y-F + T-V) showing better efficacy. The IC6 method resulted in the widest biodistribution within the brain, indicating enhanced utility of the capsid modified AAV8 variant for therapeutic purposes.
Review
Biotechnology & Applied Microbiology
Jerry R. Mendell, Samiah A. Al-Zaidy, Louise R. Rodino-Klapac, Kimberly Goodspeed, Steven J. Gray, Christine N. Kay, Sanford L. Boye, Shannon E. Boye, Lindsey A. George, Stephanie Salabarria, Manuela Corti, Barry J. Byrne, Jacques P. Tremblay
Summary: Hereditary diseases are caused by gene mutations, affecting millions of Americans, and gene therapy using adeno-associated virus (AAV) has shown promise in treating these diseases. Five treatments have been approved for commercialization, with many more in clinical trials, showcasing the potential of gene therapy in treating a wide range of genetic disorders.
Article
Virology
Sean M. Crosson, Antonette Bennett, Diego Fajardo, James J. Peterson, Hangning Zhang, Wei Li, Matthew T. Leahy, Colin K. Jennings, Ryan F. Boyd, Sanford L. Boye, Mavis Agbandje-McKenna, Shannon E. Boye
Summary: Rationally designed AAV2-based capsid variants with specific hydrophilic and hydrophobic amino acid mutations can significantly enhance retinal transduction, especially when considering the impact of these mutations on HSPG binding and vector tropism in a clinically relevant animal model.
JOURNAL OF VIROLOGY
(2021)
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
Biotechnology & Applied Microbiology
Xiajie Ma, Emily R. Sechrest, Diego Fajardo, Ping Zhu, Frank Dyka, Yixiao Wang, Ekaterina Lobanova, Shannon E. Boye, Wolfgang Baehr, Wen-Tao Deng
Summary: The study demonstrates that AAV-mediated gene augmentation therapy can rescue cone structure and function in a mouse model with a congenital opsin deletion, emphasizing the importance of early intervention for successful therapy.
HUMAN GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Stephen R. Russell, Arlene Drack, Artur Cideciyan, Samuel G. Jacobson, Bart P. Leroy, Caroline Van Cauwenbergh, Allen C. Ho, Alina Dumitrescu, Ian C. Han, Mitchell Martin, Wanda L. Pfeifer, Elliott H. Sohn, Jean Walshire, Alexandra Garafalo, Arun K. Krishnan, Christian A. Powers, Alexander Sumaroka, Alejandro J. Roman, Eva Vanhonsebrouck, Eltanara Jones, Fanny Nerinckx, Julie De Zaeytijd, Rob W. J. Collin, Carel Hoyng, Peter Adamson, Michael E. Cheetham, Michael R. Schwartz, Wilhelmina den Hollander, Friedrich Asmus, Gerard Platenburg, David Rodman, Aniz Girach
Summary: The translation content introduces the results of a clinical trial on the treatment of CEP290-associated LCA10 with sepofarsen. Although patients experienced ocular adverse events in the treated eye, the lower dose group showed a better benefit-risk profile. The trial results suggest that the use of sepofarsen may improve patients' visual acuity and retinal sensitivity.
Article
Ophthalmology
Alejandro J. Roman, Artur V. Cideciyan, Vivian Wu, Abraham A. Mascio, Arun K. Krishnan, Alexandra V. Garafalo, Samuel G. Jacobson
Summary: This study developed a mobility task to quantify functional vision in patients with LCA. Combined with other measurements of rod and cone photoreceptor-mediated vision, dark-adapted functional vision can provide a more comprehensive understanding of the natural history and treatment effects in LCA patients.
Article
Biology
Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron DiAntonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt