Review
Biochemistry & Molecular Biology
Lyes Toualbi, Maria Toms, Mariya Moosajee
Summary: Inherited retinal diseases (IRDs) are a group of disorders causing progressive vision loss and affecting approximately one in 1000 people worldwide. While gene augmentation therapy using viral vectors has shown promise, non-viral gene augmentation strategies using plasmids with minimal bacterial backbones and S/MAR sequences offer potential advantages such as accommodating larger genes and reducing immune responses. Despite challenges like low retinal transfection rates, various approaches including using nanoparticles and electrical methods show promise in preclinical studies, suggesting non-viral gene therapy as a safer and effective option for future IRD treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Endocrinology & Metabolism
Zhongjie Fu, Lois E. H. Smith
Summary: Pathologic angiogenesis in eye diseases leading to blindness can be attributed to cell senescence, as demonstrated by the bioinformatics study conducted by Crespo-Garcia, Tsuruda, and Dejda. Their findings were validated in human and mouse retina models, where clearance of senescent cells effectively suppressed neovessel growth.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2021)
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
Pharmacology & Pharmacy
Song Yang, Jun Zhou, Dengwen Li
Summary: The retinal pigment epithelium is crucial for visual functions, but damage to its structure and function can lead to various retinopathies with no cure currently available. Understanding the development, function, and pathobiology of the retinal pigment epithelium is essential for preventing and treating retinopathies. This review discusses potential strategies for treatment and provides new perspectives for future research in this field.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Albert M. Maguire, Jean Bennett, Elena M. Aleman, Bart P. Leroy, Tomas S. Aleman
Summary: Luxturna, the first FDA-approved gene therapy product for a genetic disease, has reversed blindness in individuals with retinal degenerative disease. It has not only transformed the lives of many previously destined to live a life of blindness, but also sparked interest in developing gene therapy treatments for other inherited retinal diseases.
Article
Immunology
Inbal Benhar, Jiarui Ding, Wenjun Yan, Irene E. Whitney, Anne Jacobi, Malika Sud, Grace Burgin, Karthik Shekhar, Nicholas M. Tran, Chen Wang, Zhigang He, Joshua R. Sanes, Aviv Regev
Summary: Non-neuronal cells play a vital role in the intricate cellular interactions following central nervous system damage. By analyzing immune, glial, and retinal pigment epithelial cells from adult mouse retina at different time points after axonal transection, we identified rare subsets and delineated injury-induced changes in cell composition, expression programs, and interactions. Computational analysis revealed a three-phase inflammatory cascade after injury, involving reactivation of retinal macroglia and microglia in the early phase, differentiation of infiltrating monocytes into macrophages in the intermediate phase, and inflammatory resolution in the late phase. Our findings provide insights into the cellular circuitry, spatial relationships, and molecular interactions following tissue injury.
Article
Pharmacology & Pharmacy
Jinyuan Luo, Greymi Tan, Kai Xin Thong, Konstantinos N. Kafetzis, Neeru Vallabh, Carl M. Sheridan, Yusuke Sato, Hideyoshi Harashima, Aristides D. Tagalakis, Cynthia Yu-Wai-Man
Summary: This study demonstrates the successful delivery of MRTF-B siRNA into human trabecular meshwork cells using a novel lipid nanoparticle (LNP). The results show that both LNP formulations effectively silenced the MRTF-B gene without cytotoxicity. The study also found that LNP significantly reduced cell contractility. These findings suggest that LNP could be a promising non-viral gene therapy for preventing fibrosis in minimally invasive glaucoma surgery (MIGS).
Article
Nanoscience & Nanotechnology
Hannah J. Vaughan, Camila G. Zamboni, Kathryn M. Luly, Ling Li, Kathleen L. Gabrielson, Laboni F. Hassan, Nicholas P. Radant, Pranshu Bhardwaj, Florin M. Selaru, Martin G. Pomper, Jordan J. Green
Summary: This study investigated a new approach of local delivery of polymeric nanoparticles (NPs) via intra-arterial injection for targeted local gene delivery to hepatocellular carcinoma (HCC) tumors. The results showed that this method had a better effect in treating HCC compared to intravenous administration.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Ophthalmology
Line Kessel, Ulrik Correll Christensen, Kristian Klemp
Summary: This study retrospectively analyzed the prevalence of intraocular inflammation in patients receiving subretinal gene therapy. The results showed that vitritis was observed in 9 out of 23 eyes, and some eyes also had outer retinal infiltrates. The inflammation could be alleviated with immunosuppressant therapy, but close monitoring is necessary. Inflammation did not have a significant adverse effect on visual function, but it could lead to atrophy of the retinal pigment epithelium and outer retina.
Article
Chemistry, Multidisciplinary
Sun Young Park, Kangmin Park, Jin-Woo Oh, Geuntae Park
Summary: This paper presents a method for synthesizing Tagetes erecta L. gold nanoparticles (TE-GNPs) using an aqueous extract of Tagetes erecta L. The extract serves as a reducing and stabilizing agent with significant antioxidant activity. The TE-GNPs are successfully synthesized and characterized through spectroscopy and microscopy techniques, demonstrating their nanoscale dimensions, stability, and crystalline nature.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Antoine Hakim, Benjamin Guido, Lokesh Narsineni, Ding-Wen Chen, Marianna Foldvari
Summary: Glaucoma is a progressive disease caused by the death of retinal ganglion cells and axonal loss in the optic nerve. Elevated intraocular pressure is a major risk factor contributing to this condition. Current management mainly focuses on lowering intraocular pressure, but it does not address optic nerve degeneration. Gene therapy, especially non-viral delivery systems, shows promise in controlling genes involved in glaucoma pathophysiology and providing neuroprotection.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Cell Biology
Jinying Li, Chen Qiu, Yang Wei, Weixin Yuan, Jia Liu, Wenyu Cui, Jiayi Zhou, Cong Qiu, Lihe Guo, Liquan Huang, Zhen Ge, Luyang Yu
Summary: Human amniotic epithelial stem cells can differentiate into RPE like cells with the help of trichostatin A and nicotinamide, showing potential therapeutic effects for age-related macular degeneration. Subretinal transplantation of these cells in RCS rats resulted in rescued visual function and retinal structure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Ophthalmology
M. Helena Cardoso, Michael J. Hall, Thomas Burgoyne, Pedro Fale, Tina Storm, Cristina Escrevente, Pedro Antas, Miguel C. Seabra, Clare E. Futter
Summary: This study aimed to model the effects of chloroquine on the retinal pigment epithelium in vivo and investigate the impact of mild chloroquine treatment on lysosome function and turnover. The research found that low-dose chloroquine treatment inhibits lysosome reformation, leading to a gradual depletion of lysosomes' ability to interact with cargo-carrying vacuoles and degrade their content. The accumulation of pro-cathepsin D and LAMP1 reflects the inhibition of normal turnover of lysosomal constituents and possibly lysosomes themselves. Understanding the mechanisms underlying lysosome reformation may contribute to the development of new treatments for chloroquine-induced retinopathy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Cell Biology
Miwa Hara, Hara Wenjing, Volha V. Malechka, Yusuke Takahashi, Jian-Xing Ma, Gennadiy Moiseyev
Summary: PNPLA2 acts as a phospholipase in the endoplasmic reticulum, mobilizing retinyl esters from retinosomes and playing a crucial role in the visual cycle.
Article
Pharmacology & Pharmacy
Sepanta Hosseinpour, Maria Natividad Gomez-Cerezo, Yuxue Cao, Chang Lei, Huan Dai, Laurence J. Walsh, Saso Ivanovski, Chun Xu
Summary: This study compared the capacity of mesoporous bioactive glass nanoparticles and mesoporous silica nanoparticles to deliver miRNA to bone marrow mesenchymal stem cells, demonstrating that mesoporous bioactive glass nanoparticles had a stronger osteogenic effect.
Article
Engineering, Biomedical
Lin-Lin Luo, Jie Xu, Bing-Qiao Wang, Chen Chen, Xi Chen, Qiu-Mei Hu, Yu-Qiu Wang, Wan-Yun Zhang, Wan-Xiang Jiang, Xin-Ting Li, Hu Zhou, Xiao Xiao, Kai Zhao, Sen Lin
Summary: A novel AAV serotype, AAVYC5, introduced in this study, showed more efficient transduction into multiple retinal layers compared to AAV2, and enabled successful delivery of anti-angiogenic molecules in mice and non-human primates.