Article
Cell & Tissue Engineering
Eric D. Jong, Sabiha Hacibekiroglu, Lily Guo, Evan Sawula, Biao Li, Chengjin Li, Margaret T. Ho, Molly S. Shoichet, Valerie A. Wallace, Andras Nagy
Summary: A combined cell and gene therapy was developed for the treatment of retinitis pigmentosa (RP). Human embryonic stem cells (hESCs) were genetically engineered to differentiate into retinal pigment epithelium (hRPE) cells, which were used to protect and preserve photoreceptor cells in mouse models. This study reveals the potential of this therapy for RP treatment and the possibility of using hRPE cells for long-term delivery of therapeutic biologics.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Panpan Zhu, Jingjin Xu, Yadong Wang, Chengtian Zhao
Summary: Research reveals that deletion of the ift74 gene in zebrafish results in ciliogenesis defects in multiple organs, with photoreceptor cell degeneration occurring at a slower pace compared to other ift-b mutants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Abhishek Vats, Yibo Xi, Bing Feng, Owen D. Clinger, Anthony J. St Leger, Xujie Liu, Archisha Ghosh, Chase D. Dermond, Kira L. Lathrop, Gregory P. Tochtrop, Serge Picaud, Yuanyuan Chen
Summary: This study demonstrates the effectiveness of a nonretinoid chaperone in treating RHO-associated RP, showing improvement in retinal proteostasis and delay in photoreceptor death.
Article
Medicine, Research & Experimental
Elliot H. Choi, Susie Suh, David E. Einstein, Henri Leinonen, Zhiqian Dong, Sriganesh Ramachandra Rao, Steven J. Fliesler, Seth Blackshaw, Minzhong Yu, Neal S. Peachey, Krzysztof Palczewski, Philip D. Kiser
Summary: This study presents a novel RPE-specific knockin mouse line with accurate introduction of the CreER(T2) gene into retinal pigment epithelial cells, demonstrating high efficiency and absolute RPE-specific recombination ability for studying gene function and pathophysiology in the RPE.
Article
Biology
Xue Yang, Jin-Yong Chung, Usha Rai, Noriko Esumi
Summary: The study characterized the damage caused by sodium iodate (NaIO3) in mouse retinal pigment epithelium (RPE), which was divided into three regions: periphery with normal-shaped RPE, transitional zone with elongated cells, and center with severely damaged or lost RPE. Elongated cells in the transitional zone displayed molecular characteristics of epithelial-mesenchymal transition. Central RPE was more susceptible to stresses than peripheral RPE. Additionally, SIRT6, a protein deacylase, depletion was observed in the nucleus under stress, which could be overcome by SIRT6 overexpression in transgenic mice, protecting RPE from NaIO3-induced damage.
LIFE SCIENCE ALLIANCE
(2023)
Article
Ophthalmology
Megumi Matsuo, Makoto Matsuyama, Tomoe Kobayashi, Shinji Kanda, Satoshi Ansai, Taichi Kawakami, Erika Hosokawa, Yutaka Daido, Takehiro G. Kusakabe, Kiyoshi Naruse, Shoji Fukamachi
Summary: The study aimed to assess the effects of SWS1 deficiency on retinal structure using sws1-mutant medaka. The results showed that the deletion of SWS1 did not cause retinal degeneration and had no impact on the expression of long wavelength sensitive opsin.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Francesco Testa, Paolo Melillo, Valentina Di Iorio, Claudio Iovino, Francesco Farinaro, Marianthi Karali, Sandro Banfi, Settimio Rossi, Michele Della Corte, Francesca Simonelli
Summary: This retrospective study evaluated the quantitative retinal changes in children treated with VN using SD-OCT. The results showed significant improvement in BCVA, central foveal retinal thickness, and central foveal ONL thickness after treatment. The findings suggest that the improvement in visual acuity could be related to partial recovery of retinal morphology.
SCIENTIFIC REPORTS
(2022)
Review
Clinical Neurology
Udo Bartsch, Stephan Storch
Summary: This review discusses the key findings of different experimental approaches in NCL animal models aimed at attenuating progressive retinal degeneration and the decline in retinal function. Experimental enzyme replacement therapy, gene therapy, cell-based therapy, and immunomodulation therapy were evaluated and showed encouraging therapeutic benefits. Gene-based approaches, in particular, have shown strong potential in treating retinal dystrophies in NCLs.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Hui Peng, Prerana Ramadurgum, DaNae R. Woodard, Steffi Daniel, Emi Nakahara, Marian Renwick, Bogale Aredo, Shyamtanu Datta, Bo Chen, Rafael Ufret-Vincenty, John D. Hulleman
Summary: The DHFR DD system can be effectively applied in various mouse models of ocular diseases, providing a foundation for the conditional control of gene therapy to treat multiple eye diseases.
Article
Biochemistry & Molecular Biology
Manas R. Biswal, Zhaoyao Wang, Ryan J. Paulson, Rukshana R. Uddin, Yao Tong, Ping Zhu, Hong Li, Alfred S. Lewin
Summary: Modified form of EPO, EPO-R76E, attenuates erythropoietic activity but effectively inhibits apoptosis, oxidative stress, and inflammation in retinal degeneration. Long-term sustained delivery of EPO-R76E using AAV can prevent RPE oxidative stress-induced retinal degeneration, potentially providing a tool for preventing Age-Related Macular Degeneration.
Review
Neurosciences
Fangyuan Zhen, Tongdan Zou, Ting Wang, Yongwei Zhou, Shuqian Dong, Houbin Zhang
Summary: Rhodopsin is a light-sensitive receptor that initiates the phototransduction cascade. Mutations in the rhodopsin-encoding gene are the leading cause of retinitis pigmentosa. The high allelic heterogeneity suggests complex pathogenic mechanisms related to protein misfolding and dysfunction.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyuan Ren, Thierry Leveillard
Summary: The human retina is exposed to reactive oxygen species (ROS) from both internal and external sources, which can cause oxidative stress and lead to damage and cell death. This review focuses on the antioxidant systems in the retina and how they protect against oxidative stress. Both small antioxidants and antioxidant enzymes are involved in the removal of ROS, with the thioredoxin and glutaredoxin systems playing a major role in regulating redox signaling. Additionally, the proteins RdCVFL and TXNIP are involved in metabolic regulation and promoting survival in photoreceptors. Increasing antioxidant capacity in the retina shows promise as a therapy for inherited retinal degeneration.
Article
Ophthalmology
Bhubanananda Sahu, Laura Moreno Leon, Wei Zhang, Nikita Puranik, Ramesh Periasamy, Hemant Khanna, Michael Volkert
Summary: The study demonstrates that the human OXR1 gene can protect neurons from oxidative stress and delay photoreceptor cell death. Results from cell experiments and mouse models show that OXR1 can enhance cell resistance, reduce ROS levels and caspase cleavage, ultimately delaying retinal degeneration. OXR1 has the potential to be a therapeutic candidate for various retinal degenerative diseases targeting oxidative stress.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Neurosciences
Junling Liu, Mahmoud Bassal, Stefanie Schlichting, Ingke Braren, Alessandro Di Spoezio, Paul Saftig, Udo Bartsch
Summary: In this study, the efficacy of a cell-based enzyme substitution strategy and a gene therapy approach in attenuating retinal pathology was compared. The gene therapy approach proved to be more effective in restoring the disrupted autophagy-lysosomal pathway and attenuating retinal degeneration.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Pharmacology & Pharmacy
Xun Zhang, Reem Hasaballah Alhasani, Xinzhi Zhou, James Reilly, Zhihong Zeng, Niall Strang, Xinhua Shu
Summary: Retinal degeneration, the most common cause of visual impairment, is associated with oxysterols which regulate cholesterol homeostasis in the retina. Different oxysterols have toxic or protective roles in different types of retinal degeneration. Understanding the pathophysiology related to oxysterols will aid in the development of effective therapies for retinal degeneration.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Sylvain Darnet, Steven J. Fliesler, Hubert Schaller
JOURNAL OF LIPID RESEARCH
(2020)
Article
Cell Biology
Marci L. DeRamus, Stephanie J. Davis, Sriganesh Ramachandra Rao, Cyril Nyankerh, Delores Stacks, Timothy W. Kraft, Steven J. Fliesler, Steven J. Pittler
Article
Cell Biology
Sriganesh Ramachandra Rao, Steven J. Fliesler, Pravallika Kotla, Mai N. Nguyen, Steven J. Pittler
Article
Multidisciplinary Sciences
Sriganesh Ramachandra Rao, Lara A. Skelton, Fuguo Wu, Agnieszka Onysk, Grzegorz Spolnik, Witold Danikiewicz, Mark C. Butler, Delores A. Stacks, Liliana Surmacz, Xiuqian Mu, Ewa Swiezewska, Steven J. Pittler, Steven J. Fliesler
Article
Biochemistry & Molecular Biology
Sriganesh Ramachandra Rao, Steven J. Fliesler
Summary: This article provides an overview of cholesterol synthesis, uptake, metabolism, and efflux in the retina, focusing on studies involving animal models of monogenic disorders and in vitro models. Current knowledge gaps and opportunities for further research in this field are also identified.
JOURNAL OF LIPID RESEARCH
(2021)
Editorial Material
Ophthalmology
Steven J. Fliesler
EXPERIMENTAL EYE RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Steven J. Fliesler
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Bruce A. Pfeffer, Libin Xu, Steven J. Fliesler
Summary: Transcriptomic analysis on a SLOS animal model revealed up-regulation of pathways such as endoplasmic reticulum stress, oxidative stress, DNA damage and repair, and autophagy in cells treated with oxysterols. The two oxysterols exert their effects through different molecular mechanisms, with changes in expression of key genes confirmed by immunofluorescence confocal microscopy. These findings expand our understanding of retinal degeneration and SLOS pathobiology, identifying potential new druggable targets for therapeutic intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Min-Kyoo Shin, Edwin Vazquez-Rosa, Yeojung Koh, Matasha Dhar, Kalyani Chaubey, Coral J. Cintron-Perez, Sarah Barker, Emiko Miller, Kathryn Franke, Maria F. Noterman, Divya Seth, Rachael S. Allen, Cara T. Motz, Sriganesh Ramachandra Rao, Lara A. Skelton, Machelle T. Pardue, Steven J. Fliesler, Chao Wang, Tara E. Tracy, Li Gan, Daniel J. Liebl, Jude P. J. Savarraj, Glenda L. Torres, Hilda Ahnstedt, Louise D. McCullough, Ryan S. Kitagawa, H. Alex Choi, Pengyue Zhang, Yuan Hou, Chien-Wei Chiang, Lang Li, Francisco Ortiz, Jessica A. Kilgore, Noelle S. Williams, Victoria C. Whitehair, Tamar Gefen, Margaret E. Flanagan, Jonathan S. Stamler, Mukesh K. Jain, Allison Kraus, Feixiong Cheng, James D. Reynolds, Andrew A. Pieper
Summary: Traumatic brain injury induces tau acetylation, leading to neurodegeneration and neurobehavioral impairment. Protecting mice from TBI can be achieved by blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1. Ac-tau may serve as a therapeutic target and potential blood biomarker of TBI.
Article
Medicine, Research & Experimental
Elliot H. Choi, Susie Suh, David E. Einstein, Henri Leinonen, Zhiqian Dong, Sriganesh Ramachandra Rao, Steven J. Fliesler, Seth Blackshaw, Minzhong Yu, Neal S. Peachey, Krzysztof Palczewski, Philip D. Kiser
Summary: This study presents a novel RPE-specific knockin mouse line with accurate introduction of the CreER(T2) gene into retinal pigment epithelial cells, demonstrating high efficiency and absolute RPE-specific recombination ability for studying gene function and pathophysiology in the RPE.
Article
Cell Biology
Sriganesh Ramachandra Rao, Steven J. Fliesler
Summary: The tandem-tagged autophagy reporter mouse model is a useful tool for studying autophagy in the retina, but its application depends on various technical and biological factors, including microscope settings, transgene expression, choice of fluorophores, and the presence of lipofuscin autofluorescence.
Article
Neurosciences
Rachael S. Allen, Cara T. Motz, Anayesha Singh, Andrew Feola, Lauren Hutson, Amber Douglass, Sriganesh Ramachandra Rao, Lara A. Skelton, Lidia Cardelle, Katie L. Bales, Kyle Chesler, Kaavya Gudapati, C. Ross Ethier, Matthew M. Harper, Steven J. Fliesler, Machelle T. Pardue
Summary: The configuration of animal holders used in blast exposure studies significantly affects outcomes, with enclosed holders potentially causing secondary damage to the contralateral eye and open holders potentially damaging the brain through rapid head movement.
Editorial Material
Ophthalmology
Bruce A. A. Pfeffer, Steven J. J. Fliesler
EXPERIMENTAL EYE RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Steven J. Fliesler, Sriganesh Ramachandra Rao, Mai N. Nguyen, Mahmoud Tawfik KhalafAllah, Steven J. Pittler
Summary: This review focuses on the phenotypic characteristics and genetic mutations of RP59 models and patients. The ocular phenotypes are particularly emphasized. The findings address knowledge gaps in the underlying pathobiology mechanism of RP59 and have potential implications for developing therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Khanichi N. Charles, Janis E. Shackelford, Phyllis L. Faust, Steven J. Fliesler, Herbert Stangl, Werner J. Kovacs
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
