中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (3): 815-816.doi: 10.4103/NRR.NRR-D-24-00133

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

青光眼和视神经损伤的单基因治疗

  

  • 出版日期:2025-03-15 发布日期:2024-06-26

Monogenic gene therapy for glaucoma and optic nerve injury

Chikako Harada, Xiaoli Guo, Takayuki Harada*   

  1. Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
  • Online:2025-03-15 Published:2024-06-26
  • Contact: Takayuki Harada, MD, PhD, harada-tk@igakuken.or.jp.
  • Supported by:
    This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grants-in-Aid for Scientific Research (JP22K09804 to CH; JP21K09688 to XG; JP19KK0229, JP21H04786, JP21H02819 and JP21K18279 to TH), the Shiseido Female Researcher Science Grant (to XG), Mitsubishi Foundation and Takeda Science Foundation (to TH).

摘要: https://orcid.org/0000-0001-6167-0997 (Takayuki Harada)

Abstract: The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells (RGCs) causes visual field defects and eventual blindness. Elevated intraocular pressure (IOP) stands out as the best-known factor affecting glaucoma. However, there exists a subtype of glaucoma, known as normal tension glaucoma, that is not associated with high IOP. A recent study has identified various factors involved in glaucoma pathogenesis, including altered retinal blood flow, glutamate neurotoxicity, oxidative stress, and others (Shinozaki et al., 2024). Furthermore, glaucoma patients may exhibit reduced amounts of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) or ciliary neurotrophic factor compared with age-matched controls. Studies indicate that intraocular injections of BDNF can rescue RGCs in a mouse model of optic nerve crush (ONC) through activation of its high-affinity receptor Tropomyosin receptor kinase B (TrkB). However, the transient nature of ligand-dependent activation poses limitations on the efficacy of this treatment. We have developed several systems, described in the following sections, to address and overcome these limitations.