1. Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma.
- Author
-
Li CP, Wu S, Sun YQ, Peng XQ, Gong M, Du HZ, Zhang J, Teng ZQ, Wang N, and Liu CM
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Cell Survival genetics, Semaphorins metabolism, Semaphorins genetics, N-Methylaspartate metabolism, Retinal Ganglion Cells metabolism, Retinal Ganglion Cells pathology, LIM-Homeodomain Proteins metabolism, LIM-Homeodomain Proteins genetics, Glaucoma genetics, Glaucoma pathology, Glaucoma metabolism, Transcription Factors metabolism, Transcription Factors genetics, Axons metabolism, Axons pathology, Disease Models, Animal, Nerve Regeneration genetics, Nerve Regeneration physiology
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF