Spatiotemporal distribution of chondroitin sulfate proteoglycans after optic nerve injury in rodents

Exp Eye Res. 2020 Jan:190:107859. doi: 10.1016/j.exer.2019.107859. Epub 2019 Nov 6.

Abstract

The accumulation of chondroitin sulfate proteoglycans (CSPGs) in the glial scar following acute damage to the central nervous system (CNS) limits the regeneration of injured axons. Given the rich diversity of CSPG core proteins and patterns of GAG sulfation, identifying the composition of these CSPGs is essential for understanding their roles in injury and repair. Differential expression of core proteins and sulfation patterns have been characterized in the brain and spinal cord of mice and rats, but a comprehensive study of these changes following optic nerve injury has not yet been performed. Here, we show that the composition of CSPGs in the optic nerve and retina following optic nerve crush (ONC) in mice and rats exhibits an increase in aggrecan, brevican, phosphacan, neurocan and versican, similar to changes following spinal cord injury. We also observe an increase in inhibitory 4-sulfated (4S) GAG chains, which suggests that the persistence of CSPGs in the glial scar opposes the growth of CNS axons, thereby contributing to the failure of regeneration and recovery of function.

Keywords: Extracellular matrix; Glycosaminoglycan sulfation; Immunocytochemistry; Optic nerve crush.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / metabolism
  • Animals
  • Brevican / metabolism
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Crush Injuries / metabolism*
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Glycosaminoglycans / metabolism
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Neurocan / metabolism
  • Optic Nerve / metabolism*
  • Optic Nerve Injuries / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Retina / metabolism*
  • Sulfamonomethoxine
  • Trimethoprim
  • Versicans / metabolism

Substances

  • Aggrecans
  • Brevican
  • Chondroitin Sulfate Proteoglycans
  • Drug Combinations
  • Glycosaminoglycans
  • Neurocan
  • Versicans
  • sulfaton
  • Trimethoprim
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5
  • Sulfamonomethoxine