Article
Biochemistry & Molecular Biology
Jacqueline Kajtna, Stephen H. Tsang, Susanne F. Koch
Summary: This study used a mouse model of retinitis pigmentosa (RP) to demonstrate that genetic rescue can halt photoreceptor degeneration and functional decline, as well as inner retinal remodeling, when fewer than 13% of rods remain. Treatment at 16 weeks of age or earlier resulted in restored visual function, while no efficacy was observed in mice treated at 24 weeks of age. Remodeling in the retinal pigment epithelium and retinal vasculature was not halted, but there was some slowing of blood vessel degradation. These findings provide insights into the potential and limitations of RP treatment and suggest nonphotoreceptor targets for gene therapy optimization.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yunlu Xue, Xiaomei Sun, Sean K. Wang, Gayle B. Collin, Vladimir J. Kefalov, Constance L. Cepko
Summary: Retinitis pigmentosa (RP) is an ocular disease characterized by the loss of night vision, followed by the loss of daylight vision. The timing of cone electroretinogram (ERG) decline in RP mouse models was investigated using physiological assays, and a correlation with the loss of rods was found. Abnormally high chromophore supply to cones upon the loss of rods is toxic to cones, suggesting a potential therapy in some forms of RP to slow down the turnover or reduce the level of visual chromophore in the retina.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Andy Shao, Antonio Jacobo Lopez, JiaJia Chen, Addy Tham, Seanne Javier, Alejandra Quiroz, Sonia Frick, Edward M. Levine, K. C. Kent Lloyd, Brian C. Leonard, Christopher J. Murphy, Thomas M. Glaser, Ala Moshiri
Summary: This study shows that the loss of Arap1 gene is related to the occurrence of retinitis pigmentosa (RP). Arap1 is not expressed in photoreceptors themselves, but is expressed in Mu'' ller glia and retinal pigment epithelium (RPE). By knocking out the Arap1 gene in RPE, the study demonstrates that the function of Arap1 in RPE phagocytosis is necessary for the survival of photoreceptors.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Tongdan Zou, Ting Wang, Fangyuan Zhen, Xu He, Shuqian Dong, Houbin Zhang
Summary: Exogenous expression of PDE5 prevents photoreceptor degeneration and promotes outer segment development in RD1 mice. Unlike the photoreceptor-specific PDE6, PDE5 shows different distribution and expression patterns. Lowering cGMP levels in photoreceptors rescues photoreceptors in RD1 retinas.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ana Artero-Castro, Kathleen Long, Andrew Bassett, Almudena Avila-Fernandez, Marta Corton, Antonio Vidal-Puig, Pavla Jendelova, Francisco Javier Rodriguez-Jimenez, Eleonora Clemente, Carmen Ayuso, Slaven Erceg
Summary: Hereditary retinal dystrophies are a significant cause of blindness due to lack of effective treatments. Patient-derived human-induced pluripotent stem cells can potentially provide autologous cells for therapy, but the presence of gene mutations remains a challenge.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Wei Du, Jiarui Li, Xin Tang, Wenzhen Yu, Mingwei Zhao
Summary: In this study, a CRISPR/SaCas9-mediated gene reduction system was developed to inactivate Rho gene mutation and replace normal rhodopsin in a specific mouse model, leading to improved retinal function. These findings suggest that CRISPR/SaCas9-based reduction and replacement gene therapy could potentially offer therapeutic benefits for Rho mutant ADRP.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Alonso Sanchez-Cruz, Andrea C. Mendez, Ignacio Lizasoain, Pedro de la Villa, Enrique J. de la Rosa, Catalina Hernandez-Sanchez
Summary: The research indicates that TLR2 plays a key role in the progression of retinitis pigmentosa (RP). Complete elimination of Tlr2 can help alleviate the loss of visual function and mitigate the loss of photoreceptor cell numbers in RP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Merve Sen, Oksana Kutsyr, Bowen Cao, Sylvia Bolz, Blanca Arango-Gonzalez, Marius Ueffing
Summary: Misfolding mutations of Rhodopsin (RHO) are a common cause of autosomal dominant retinitis pigmentosa (adRP), and targeting the degradation processes of misfolded proteins could be a potential therapeutic approach for currently untreatable adRP patients.
Article
Biology
Ryoji Amamoto, Grace K. Wallick, Constance L. Cepko
Summary: Retinitis Pigmentosa (RP) is a progressive visual disorder caused by mutations in genes. Research has found that retinoic acid (RA) signaling is crucial for the survival of peripheral cones in the retina, providing a potential strategy for preserving cone-mediated vision.
Article
Biochemistry & Molecular Biology
Natalia Martinez-Gil, Oksana Kutsyr, Agustina Noailles, Laura Fernandez-Sanchez, Lorena Vidal, Xavier Sanchez-Saez, Carla Sanchez-Castillo, Pedro Lax, Nicolas Cuenca, Antonio G. Garcia, Victoria Maneu
Summary: P2X7R and P2X4R play important roles in retinal diseases and their expression increases during disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Harshini Surendran, Swapna Nandakumar, Vijay Bhaskar K. Reddy, Jonathan Stoddard, Varsha K. Mohan, Pramod K. Upadhyay, Trevor J. McGill, Rajarshi Pal
Summary: This study demonstrated the in vivo functionality of RPE and PRP cells derived from a clinical-grade hiPSC line, showing promise for potential regenerative cell therapies in patients. The extensively characterized RPE and PRP cells expressed specific markers and demonstrated functional activity after transplantation, indicating strong efficacy and safety data for future clinical trials.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Debora Napoli, Martina Biagioni, Federico Billeri, Beatrice Di Marco, Noemi Orsini, Elena Novelli, Enrica Strettoi
Summary: The study reveals structural abnormalities in the RPE of RP patients, leading to dysfunction of the inner barrier. Findings also suggest a correlation between the extent of photoreceptor loss and interruption zones of ZO-1. Treatment with dexamethasone in RP mice not only rescues cones but also restores RPE structure, highlighting a potential feedback loop for simultaneous protection of cones and the RPE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Rocio Garcia-Arroyo, Aleix Gavalda-Navarro, Francesc Villarroya, Gemma Marfany, Serena Mirra
Summary: CERKL, a causative gene for Retinitis Pigmentosa, is involved in regulating autophagy, stress granules, and mitochondrial metabolism. Depletion of CERKL increases vulnerability of RPE mitochondria, leading to altered mitochondrial shape and respiratory dysfunction under oxidative stress conditions. Overexpression of CERKL protects the mitochondrial network against oxidative stress, suggesting its resilience in regulating mitochondrial function in RPE cells.
Article
Ophthalmology
Yang Liu, Xin Wang, Ruowen Gong, Gezhi Xu, Min Zhu
Summary: Overexpression of WT RHO and its mutants leads to energy failure and cell death, with distinct impacts on the two energy metabolic pathways.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Cell Biology
Ying Kai Chan, Sean K. Wang, Colin J. Chu, David A. Copland, Alexander J. Letizia, Helena Costa Verdera, Jessica J. Chiang, Meher Sethi, May K. Wang, William J. Neidermyer, Yingleong Chan, Elaine T. Lim, Amanda R. Graveline, Melinda Sanchez, Ryan F. Boyd, Thomas S. Vihtelic, Rolando Gian Carlo O. Inciong, Jared M. Slain, Priscilla J. Alphonse, Yunlu Xue, Lindsey R. Robinson-McCarthy, Jenny M. Tam, Maha H. Jabbar, Bhubanananda Sahu, Janelle F. Adeniran, Manish Muhuri, Phillip W. L. Tai, Jun Xie, Tyler B. Krause, Andyna Vernet, Matthew Pezone, Ru Xiao, Tina Liu, Wei Wang, Henry J. Kaplan, Guangping Gao, Andrew D. Dick, Federico Mingozzi, Maureen A. McCall, Constance L. Cepko, George M. Church
Summary: The study engineered AAV vectors by incorporating short DNA oligonucleotides to antagonize TLR9 activation, reducing innate immune responses and enhancing gene expression in clinically relevant animal models. The engineered vectors can avoid adverse reactions in some models, demonstrating a potential wider therapeutic window for AAV therapies.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biology
Yunlu Xue, Sean K. Wang, Parimal Rana, Emma R. West, Christin M. Hong, Helian Feng, David M. Wu, Constance L. Cepko
Summary: Research has found that an adeno-associated virus vector expressing the Txnip gene can prolong the survival of cone photoreceptors and improve vision in RP mouse models. Additionally, a Txnip allele called C247S offers even greater benefits, and the rescue effect of Txnip relies on lactate dehydrogenase b (Ldhb).
Review
Immunology
Sean K. Wang, Constance L. Cepko
Summary: This review discusses the roles of microglia in various eye disorders and explores the potential of targeting microglia for disease treatment. Different approaches include depleting microglia, reprogramming microglia, and inhibiting their downstream effects. Future research is needed to fully utilize the therapeutic value of microglia in eye diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Maryna Ivanchenko, Artur A. Indzhykulian, David P. Corey
Summary: Hair cells in the vertebrate inner ear have actin-filled protrusions called stereocilia which mediate mechanosensitivity. Hereditary deafness is often linked to abnormalities in stereocilia bundles, making them essential for understanding genetic hearing loss models. Electron microscopy techniques, such as TEM and SEM, are crucial for studying stereocilia morphology and protein localization.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Sean K. Wang, Edward Korot, Moosa Zaidi, Marco H. Ji, Ahmad Al-Moujahed, Natalia F. Callaway, Jochen Kumm, Darius M. Moshfeghi
Summary: The treatment outcomes in retinopathy of prematurity (ROP) are influenced by the location of the disease, with poorer outcomes in more posterior zones. This study estimated the area of Zone I in relation to various ocular parameters and found that variability in eye size and refractive power may affect the zoning. The findings suggest potential implications for optimizing treatment decisions for ROP.
SCIENTIFIC REPORTS
(2022)
Correction
Biotechnology & Applied Microbiology
Robert Chen, Sean K. Wang, Julia A. Belk, Laura Amaya, Zhijian Li, Angel Cardenas, Brian T. Abe, Chun-Kan Chen, Paul A. Wender, Howard Y. Chang
NATURE BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Robert Chen, Sean K. Wang, Julia A. Belk, Laura Amaya, Zhijian Li, Angel Cardenas, Brian T. Abe, Chun-Kan Chen, Paul A. Wender, Howard Y. Chang
Summary: In this study, a systematic approach was developed to optimize vector design and enhance protein expression from circRNAs. The optimized circRNAs showed increased translation in vitro, durable translation in vivo, and can be applied to multiple transgenes.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Marco H. Ji, Moosa Zaidi, Zachary Bodnar, Sean K. Wang, Jochen Kumm, Darius M. Moshfeghi
Summary: The study found variations in the effective composite field-of-view among different patients, but it was not correlated with the presence of ROP, gestational age, birth weight, or postmenstrual age.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Yunlu Xue, Xiaomei Sun, Sean K. Wang, Gayle B. Collin, Vladimir J. Kefalov, Constance L. Cepko
Summary: Retinitis pigmentosa (RP) is an ocular disease characterized by the loss of night vision, followed by the loss of daylight vision. The timing of cone electroretinogram (ERG) decline in RP mouse models was investigated using physiological assays, and a correlation with the loss of rods was found. Abnormally high chromophore supply to cones upon the loss of rods is toxic to cones, suggesting a potential therapy in some forms of RP to slow down the turnover or reduce the level of visual chromophore in the retina.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Maryna V. Ivanchenko, Daniel M. Hathaway, Alex J. Klein, Bifeng Pan, Olga Strelkova, Pedro De-la-Torre, Xudong Wu, Cole W. Peters, Eric M. Mulhall, Kevin T. Booth, Corey Goldstein, Joseph Brower, Marcos Sotomayor, Artur A. Indzhykulian, David P. Corey
Summary: USH1F is caused by PCDH15 mutations, leading to deafness and blindness. A gene therapy with mini-PCDH15 engineered to fit in AAV rescues hearing in mouse models of USH1F.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Ophthalmology
Christine Xu, Joel Adu-Brimpong, Henry Moshfeghi, Tatiana Rosenblatt, Michael Yu, Sean Wang, Moosa Zaidi, Hashem Ghoraba, Suzanne Michalak, Natalia Callaway, Edward Wood, Andreas Stahl, Domenico Lepore, Darius Moshfeghi
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Meeting Abstract
Ophthalmology
Sean K. Wang, Howard Y. Chang
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Meeting Abstract
Ophthalmology
Yunlu Xue, Sean Wang, Parimal Rana, Emma West, Christin Hong, Helian Feng, David M. Wu, Connie L. Cepko
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)