Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury

作者：Zhe Liu, Jingfei Xue, Canying Liu, Jiahui Tang, Siting Wu, Jicheng Lin, Jiaxu Han, Qi Zhang, Caiqing Wu, Haishun Huang, Ling Zhao, Yehong Zhuo, Yiqing Li · 发表于：Neural Regeneration Research · 年份：2023 · DOI：10.4103/1673-5374.373660 · 被引用次数：19 · 研究领域：Trace Elements in Health、Ocular Disorders and Treatments、RNA regulation and disease

Abstract JOURNAL/nrgr/04.03/01300535-202312000-00057/figure1/v/2026-05-25T161558Z/r/image-tiff Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn 2+ ) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn 2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGAT Cre ZnT3 fl/fl and VGLUT2 Cre ZnT3 fl/fl , respectively). We obtained direct evidence that the rapidly increased mobile Zn 2+ in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn...