About this item:

120 Views | 1,604 Downloads

Author Notes:

Correspondence to: Eldon E. Geisert, Emory University, 1365B Clifton Road NE; Atlanta GA 30322; Phone: (404) 778-4239; FAX: (404) 778-2231; email: egeiser@emory.edu

The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Subject:

Research Funding:

This study was supported by an Unrestricted Grand from Research to Prevent Blindness, NEI grant R01EY017841 (E.E.G.), W81XWH-12–1-0225 (E.E.G.) Owens Family Glaucoma Research Fund, P30EY006360 (Emory Vision Core).

We thank the Emory Viral Vector Core for the production of AAV (NINDS Core Facilities Grant P30NS055077) and the Emory Integrated Genomics Core (subsidized by the Emory University School of Medicine and NIH UL1TR002378).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Ophthalmology
  • RETINAL GANGLION-CELLS
  • CNS AXON REGENERATION
  • RNA-BINDING PROTEIN
  • PROMOTES REGENERATION
  • IN-VIVO
  • SYSTEMS GENETICS
  • GROWTH-STATE
  • ADULT CNS
  • INJURY
  • EXPRESSION

Optic nerve regeneration in the mouse is a complex trait modulated by genetic background

Tools:

Journal Title:

Molecular Vision

Volume:

Volume 24

Publisher:

, Pages 174-186

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains (C57BL/6J and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods: To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adenoas-sociated virus (AAV) delivery of shRNA, and a mild inflammatory response was induced with an intravitreal injection of zymosan with CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by cholera toxin B, and 2 days later, the regenerating axons within the optic nerve were examined. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that five axons had grown down the nerve and the longest distance a single axon reached. Results: The analysis revealed a considerable amount of differential axonal regeneration across the seven BXD strains and the parental strains. There was a statistically significant difference (p=0.014 Mann–Whitney U test) in the regenerative capacity in the number of axons reaching 0.5 mm from a low of 236.1±24.4 axons in the BXD102 mice to a high of 759.8±79.2 axons in the BXD29 mice. There were also statistically significant differences (p=0.014 Mann–Whitney U test) in the distance axons traveled. Looking at a minimum of five axons, the shortest distance was 787.2±46.5 µm in the BXD102 mice, and the maximum distance was 2025.5±223.3 µm in the BXD29 mice. Conclusions: Differences in genetic background can have a profound effect on axonal regeneration causing a threefold increase in the number of regenerating axons at 0.5 mm from the crush site and a 2.5-fold increase in the distance traveled by at least five axons in the damaged optic nerve.

Copyright information:

© 2018 Molecular Vision.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote