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    Date Issued2021 (1)2020 (1)AuthorLi, Xiaorong (2)Lin, Haijiang (2)Su, Wenqi (2)
    Sun, Shuo (2)
    Tian, Bo (2)View MoreUMass Chan AffiliationDepartment of Ophthalmology and Visual Sciences (2)Department of Microbiology and Physiological Systems (1)Horae Gene Therapy Center (1)Li Weibo Institute for Rare Diseases Research (1)Viral Vector Core (1)Document TypeJournal Article (2)KeywordEye Diseases (2)Ophthalmology (2)anti-VEGF (1)corneal neovascularization (1)COVID-19 (1)View MoreJournalDiscovery medicine (1)Molecular therapy. Methods and clinical development (1)

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    Efficacious, safe, and stable inhibition of corneal neovascularization by AAV-vectored anti-VEGF therapeutics

    Su, Wenqi; Sun, Shuo; Tian, Bo; Tai, Phillip W. L.; Luo, Yongwen; Ko, Jihye; Zhan, Wei; Ke, Xiao; Zheng, Qiang; Li, Xiaorong; et al. (2021-06-24)
    Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8-KH902 far exceeded that of rAAV2-KH902. A single-dose rAAV8-KH902 treatment at 8 x 10(8) genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10-14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8-KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV.
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    COVID-19: the novel coronavirus disease and its manifestations and management in ophthalmology

    Sun, Shuo; Su, Wenqi; Lin, Christopher Q.; Li, Xiaorong; Yan, Hua; Tian, Bo; Lin, Haijiang (2020-05-28)
    Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.
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