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
Neurosciences
Chulbul M. Ahmeda, Michael T. Massengill, Cristhian J. Ildefonso, Archana Jalligampala, Ping Zhu, Hung Li, Anil P. Patel, Maureen A. McCall, Alfred S. Lewin
Summary: This study found that AAV-RHO820-shRNA820 can slow the loss of photoreceptor cells and preserve retinal function in P23H RHO transgenic mice. Moreover, the untreated contralateral eyes also showed the same protective effect. This suggests that RNA replacement therapy may provide clinical benefit to both eyes of adRP patients.
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
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
Medicine, Research & Experimental
Sean K. Wang, Yunlu Xue, Constance L. Cepko
Summary: Microglial phagocytosis is upregulated during cone degeneration in retinitis pigmentosa, suggesting that the expression of the CD47 signal may protect cones. Augmentation of CD47/SIRP alpha signaling could be a potential treatment strategy for RP and other forms of neurodegeneration.
Review
Biochemistry & Molecular Biology
Nicole C. L. Noel, Ian M. MacDonald, W. Ted Allison
Summary: Zebrafish are instrumental in generating models for photoreceptor degeneration, providing insights into causes and treatments of photoreceptor diseases. These models offer detailed information and important insights for disease research and therapeutic approaches.
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.
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
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
Biochemistry & Molecular Biology
Xing Li, Reem Hasaballah Alhasani, Yanqun Cao, Xinzhi Zhou, Zhiming He, Zhihong Zeng, Niall Strang, Xinhua Shu
Summary: Retinitis pigmentosa (RP) is a visual disorder caused by mutations in over 70 genes, characterized by degeneration of rod cells and cone cell death. Treatment with Gypenosides (Gyp) reduced cone cell death in rpgrip1 mutant zebrafish by decreasing oxidative stress and inflammation, promoting antioxidant gene expression, and reducing endoplasmic reticulum stress and proinflammatory cytokines expression. This suggests that Gyp may be beneficial in treating RP patients.
Article
Medicine, Research & Experimental
Ziyang Huang, Qiuling Huang, Kai Xu, Lina Liang, Yamin Li, Wei Zhou, Na Ning, Jiewen Zhou, Jiajia Hu, Shanshan Liu, Lei Dang
Summary: The aim of this study was to investigate the protective effect of Zhangyanming Tablets (ZYMT) on a mouse model of Retinitis pigmentosa (RP) and explore the underlying mechanism. The results showed that ZYMT significantly improved retinal function and structure, reduced cell apoptosis, and regulated the expressions of antioxidant and anti-/pro-apoptotic factors. Therefore, this study indicated that ZYMT has a protective effect on retinal function and morphology of inherited RP mice in the early stage.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Jason C. Park, Oksana Persidina, Giri Balasubramanian, Tara Nguyen, Anubhav Pradeep, John R. Hetling, J. Jason McAnany
Summary: This study evaluated the changes in full-field flash and flicker electroretinogram (ERG) that accompany normal aging in mice. The results showed a significant decrease in the amplitude of a-wave and b-wave over time, but no significant effect on response timing. These findings provide important guidance for future pre-clinical therapeutic studies.
SCIENTIFIC REPORTS
(2023)
Article
Ophthalmology
Xuan-Thanh-An Nguyen, Jan Koopman, Maria M. van Genderen, Henk L. M. Stam, Camiel J. F. Boon
Summary: The study found that OrCam mainly improves reading domains in patients with advanced stages of RP or CRD. Following OrCam testing, significant improvements were observed in various aspects, and some patients continued rehabilitation with OrCam after the study.
ACTA OPHTHALMOLOGICA
(2022)
Article
Pharmacology & Pharmacy
Saba Shahin, Hui Xu, Bin Lu, Augustus Mercado, Melissa K. Jones, Benjamin Bakondi, Shaomei Wang
Summary: Retinitis pigmentosa (RP) is a group of inherited retinal degenerative disorders. Gene therapy has been effective in treating autosomal recessive RP, but limited options are available for autosomal dominant RP. In vivo gene editing may be a therapeutic option, and this study shows the successful rescue of vision in rats with autosomal dominant RP through AAV delivery of a CRISPR/Cas9 construct.
Article
Biochemistry & Molecular Biology
Lorena Fuentes-Broto, Lorena Perdices, Francisco Segura, Elvira Orduna-Hospital, Gema Insa-Sanchez, Ana Sanchez-Cano, Nicolas Cuenca, Isabel Pinilla
Summary: Retinitis pigmentosa (RP) is characterized by progressive loss of visual function, primarily affecting photoreceptors. Melatonin treatment showed beneficial effects on visual function, circadian rhythm, and oxidative stress in RP animal models and wild-type rats, suggesting its potential therapeutic value in age-related visual damage.
Article
Medicine, Research & Experimental
David M. Wu, Xuke Ji, Maryna Ivanchenko, Michelle Chung, Mary Piper, Parimal Rana, Sean K. Wang, Yunlu Xue, Emma West, Sophia R. Zhao, Hongbin Xu, Marcelo Cicconet, Wenjun Xiong, Constance L. Cepko
Summary: Overexpression of Nrf2 in the RPE can rescue RPE and cone photoreceptors in mice, improve visual acuity, and reverse declines in oxidative defense pathways. This method may be a potential therapy for diseases involving RPE degeneration.
Article
Cell Biology
Emma R. West, Sylvain W. Lapan, ChangHee Lee, Kathrin M. Kajderowicz, Xihao Li, Constance L. Cepko
Summary: This study provides a comprehensive analysis of bipolar subtypes in the mouse retina, revealing the ordered birthdates and spatial distribution patterns of these subtypes. The study also suggests clonal restriction on the production of homotypic subtypes. These findings shed light on the development of neuronal subtypes and establish a framework for studying subtype diversification.
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
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)
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.
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
Biology
John G. Dingus, Jonathan C. Y. Tang, Ryoji Amamoto, Grace K. Wallick, Constance L. Cepko, Liqun Luo
Summary: Conventional antibodies and their derived fragments face challenges in targeting intracellular sites in live cells due to their larger size and complex structure. In contrast, nanobodies offer an alternative approach with documented success in intracellular expression. However, a systematic study on the intracellular expression of nanobodies has been lacking. This study investigated the intracellular expression of 75 nanobodies from the Protein Data Bank and found that a majority of them were unstable in cells, leading to aggregation and clearance. By using comparative analysis and framework mutagenesis, a general approach was developed to stabilize these originally unstable nanobodies without compromising their target binding. The stability of the mutated nanobodies extended to in vivo contexts, demonstrating the potential for improved nanobody engineering in intracellular applications. This study contributes to the growing field of intracellular interrogation and intervention.
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)
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)
Article
Biochemical Research Methods
Jocelyn Y. Kishi, Ninning Liu, Emma R. West, Kuanwei Sheng, Jack J. Jordanides, Matthew Serrata, Constance L. Cepko, Sinem K. Saka, Peng Yin
Summary: Light-Seq is an approach that utilizes light-directed DNA barcoding for multiplexed spatial indexing in fixed cells and tissues. It enables in situ selection of multiple cell populations for sequencing, allowing analysis of rare cell types without dissociation. This method combines spatial and omics information, providing a workflow for in situ imaging, protein staining, and next generation sequencing of the same cells.