Article
Cell Biology
Magdalena Cardenas-Rodriguez, Christina Austin-Tse, Judith G. M. Bergboer, Elisa Molinari, Yuya Sugano, Ruxandra Bachmann-Gagescu, John A. Sayer, Iain A. Drummond
Summary: The phenotypic variability in CEP290 deficiencies may be attributed to genetic compensation through upregulation of genes involved in a common subcellular process, lipidated protein trafficking to cilia.
JOURNAL OF CELL SCIENCE
(2021)
Review
Ophthalmology
Bart P. Leroy, David G. Birch, Jacque L. Duncan, Byron L. Lam, Robert K. Koenekoop, Fernanda B. O. Porto, Stephen R. Russell, Aniz Girach
Summary: LCA10, caused by CEP290 mutations, is a genetic retinal disease leading to severe visual impairment in early childhood. There are currently no approved treatments, but investigational strategies include RNA editing using antisense oligonucleotides or CRISPR-based approaches. The antisense oligonucleotide therapy QR-110 has shown promising results in early trials, with ongoing phase 3 clinical trials.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2021)
Article
Cell & Tissue Engineering
Kamil Kruczek, Zepeng Qu, Emily Welby, Hiroko Shimada, Suja Hiriyanna, Milton A. English, Wadih M. Zein, Brian P. Brooks, Anand Swaroop
Summary: Mutations in the IQCB1/NPHP5 gene cause blinding disease and kidney dysfunction. In vitro disease modeling using patient-derived cells and retinal organoids revealed abnormal ciliary structure and impaired development of visual cell structures. Reduced levels of CEP290 protein were observed in all patient-derived cells. Gene augmentation therapy showed promising results in rescuing the disease phenotype in retinal organoids.
Article
Biotechnology & Applied Microbiology
Gustavo D. Aguirre, Artur Cideciyan, Valerie L. Dufour, Ana Ripolles-Garcia, Raghavi Sudharsan, Malgorzata Swider, Roman Nikonov, Simone Iwabe, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, William A. Beltran
Summary: Gene therapy using AAV-mediated NPHP5 gene augmentation successfully restores photoreceptor structure, function, and vision in a canine model of Leber congenital amaurosis, offering a potential path for translation to human treatment.
Article
Multidisciplinary Sciences
R. C. Feord, A. Gomoliszewska, A. Pienaar, J. W. Mouland, T. M. Brown
Summary: This study establishes a new method for studying cone function in mice and reveals the widespread presence of cone-opponent processing in the mouse visual system. This research provides new insights into the functional characteristics of color processing pathways in mice.
SCIENTIFIC REPORTS
(2023)
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
Ophthalmology
Timothy M. Boyce, S. Scott Whitmore, Katayoun Varzavand, Stephen R. Russell, Elliott H. Sohn, James C. Folk, Edwin M. Stone, Ian C. Han
Summary: Patients with ADNIV have a high lifetime risk of severe vision loss, with tractional retinal detachment being an important risk factor for poor vision.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Oncology
Kelly Mulfaul, Nathaniel K. Mullin, Joseph C. Giacalone, Andrew P. Voigt, Melette DeVore, Edwin M. Stone, Budd A. Tucker, Robert F. Mullins
Summary: Activation of the alternative complement pathway is a crucial event in the development of age-related macular degeneration (AMD). Uncontrolled complement activation leads to the formation of the membrane attack complex (MAC). This study demonstrates that reduced levels of complement factor H (FH) in the choroid can contribute to MAC deposition on choroidal endothelial cells (CECs), while overexpression of FH can protect against MAC deposition. These findings highlight the importance of local FH production in preventing MAC deposition in AMD.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Noor D. White, Zachary A. Batz, Edward L. Braun, Michael J. Braun, Karen L. Carleton, Rebecca T. Kimball, Anand Swaroop
Summary: The study used a probe set to capture 46 genes related to avian vision, achieving high success rates and saving sequencing resources, while avoiding the issue of chimeric assembly. By applying these data, positively selected genes in the evolution of night vision and high-speed vision were identified, providing a new perspective for evolutionary research.
MOLECULAR ECOLOGY RESOURCES
(2022)
Correction
Biotechnology & Applied Microbiology
Gustavo D. Aguirre, Artur V. Cideciyan, Valerie L. Dufour, Ana Ripolles-Garcia, Raghavi Sudharsan, Malgorzata Swider, Roman Nikonov, Simone Iwabe, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, William A. Beltran
Article
Biochemistry & Molecular Biology
Claire Marchal, Nivedita Singh, Ximena Corso-Diaz, Anand Swaroop
Summary: This article presents mathematical concepts for estimating and predicting the resolution of Hi-C datasets, and introduces HiCRes, a docker pipeline, for analyzing multiple Hi-C libraries.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Andrew J. Smith, Jayshree Advani, Daniel C. Brock, Jacob Nellissery, Jessica Gumerson, Lijin Dong, L. Aravind, Breandan Kennedy, Anand Swaroop
Summary: We identified a mitochondrial protein, GATD3A, with bacterial evolutionary affinities, that functions as a deglycase and restricts the formation of AGEs in mitochondria. GATD3A may play a role in maintaining the integrity of important biomolecules.
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
Biochemistry & Molecular Biology
Xulong Liang, Sharda P. Yadav, Zachary A. Batz, Jacob Nellissery, Anand Swaroop
Summary: During retinal development, NRL protein specifies the fate of rod photoreceptor cells by controlling the expression of genes such as Rhodopsin. Our study reveals that protein kinase CK2 can phosphorylate Ser117 residue of NRL, thereby modulating its transcriptional regulatory activity. The regulation of NRL by CK2 highlights the intricate interdependence of transcriptional and signaling pathways in maintaining the homeostasis of rod photoreceptors.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Claire Marchal, Nivedita Singh, Zachary Batz, Jayshree Advani, Catherine Jaeger, Ximena Corso-Diaz, Anand Swaroop
Summary: This study reveals the genomic regulation of the human retina using high-resolution chromatin contact maps, identifying candidate genes associated with retinal degeneration and susceptibility to eye diseases, and providing new insights into the genetic control of tissue-specific functions.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Artur Cideciyan, Samuel G. Jacobson, Alexander Sumaroka, Malgorzata Swider, Arun K. Krishnan, Rebecca Sheplock, Alexandra V. Garafalo, Karina E. Guziewicz, Gustavo D. Aguirre, William A. Beltran, Yoshitsugu Matsui, Mineo Kondo, Elise Heon
Summary: The only approved retinal gene therapy is for biallelic RPE65 mutations which cause a recessive retinopathy with a primary molecular defect located at the retinal pigment epithelium (RPE). For a distinct recessive RPE disease caused by biallelic BEST1 mutations, a pre-clinical proof-of-concept for gene therapy has been demonstrated in canine eyes. The current study was undertaken to consider potential outcome measures for a BEST1 clinical trial in patients demonstrating a classic autosomal recessive bestrophinopathy (ARB) phenotype.
Meeting Abstract
Ophthalmology
Stephen R. Russell, Arlene V. Drack, Artur V. Cideciyan, Samuel G. Jacobson, Bart P. Leroy, Caroline Van Cauwenbergh, Michael Schwartz, Aniz Girach
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
William A. Beltran, Artur V. Cideciyan, Ana Ripolles-Garcia, Valerie L. Dufour, Yu Sato, Alexa Gray, Malgorzata Swider, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, Gustavo D. Aguirre
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)