Lhx2 Promotes Axon Regeneration of Adult Retinal Ganglion Cells and Rescues Neurodegeneration in Mouse Models of Glaucoma

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2024 May 10

PMID 38729157

Authors

Chang-Ping Li

Shen Wu

Yong-Quan Sun

Xue-Qi Peng

Maolei Gong

Hong-Zhen Du

Jingxue Zhang

Zhao-Qian Teng

Ningli Wang

Chang-Mei Liu

Affiliations

Soon will be listed here.

Abstract

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.

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