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An effective pharmacological hydrogel induces optic nerve repair and improves visual function

Science China(Life Sciences) 2024年第3期67卷 529-542页

作者： Lipeng Wang Shan Zhang Yawen Han Shuo Tang Jiarui Li Lina Bu Dongyu Zhao Hongkui Deng Department of Cell Biology Schoolof Basic Medical SciencesPeking University Stem Cell Research CenterStateKey Laboratoryof Naturaland Biomimetic DrugsPeking University Health Science Center Beijing 100191China MOE Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Changping Laboratory Beijing 102206China Department of Ophthalmology Peking University People's Hospital Eye Diseases and Optometry InstituteBeijing 100871China Department of Biomedical Informatics School of Basic Medical SciencesPeking UniversityBeijing 100191China

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

关键词： retinal ganglion cell axon regeneration old-age glaucoma small molecules pharmacological hydrogel visual function repair

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