Inhibition of CRMP2 Phosphorylation Suppresses Microglia Activation in the Retina and Optic Nerve and Promotes Optic Nerve Regeneration After Optic Nerve Injury

Neuromolecular Med. 2024 Sep 12;26(1):37. doi: 10.1007/s12017-024-08805-1.

Abstract

As the primary connection between the eye and brain, the optic nerve plays a pivotal role in visual information transmission. Injuries to the optic nerve can occur for various reasons, including trauma, glaucoma, and neurodegenerative diseases. Retinal ganglion cells (RGCs), a type of neurons that extend axons through the optic nerve, can rapidly respond to injury and initiate cell death. Additionally, following optic nerve injury microglia, which serve as markers of neuroinflammation, transition from a resting state to an activated state. The phosphorylation of collapsin response mediator protein2 (CRMP2) in the semaphorin 3A (Sema3A) signalling pathway affects several processes, including axon guidance and neuron regeneration. In this study, we used an optic nerve crush (ONC) mouse model to investigate the effects of suppressing CRMP2 phosphorylation on microglia activation. We found that CRMP2 phosphorylation inhibitor suppressed RGCs loss and promoted neuronal regeneration following ONC. In addition, CRMP2 S522A mutant (CRMP2 KI) mice exhibited decreased microglial activation in both the retina and optic nerve following ONC. These results suggest that inhibiting the phosphorylation of CRMP2 can alleviate the loss of RGCs and microglial activation after optic nerve injury, providing insight into the development of treatments for optical neuropathies and neurodegenerative diseases.

Keywords: Collapsin mediator protein 2; Microglia; Optic nerve injury; Phosphorylation.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Intercellular Signaling Peptides and Proteins* / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia* / drug effects
  • Microglia* / metabolism
  • Nerve Crush
  • Nerve Regeneration* / drug effects
  • Nerve Tissue Proteins* / genetics
  • Optic Nerve Injuries* / drug therapy
  • Optic Nerve Injuries* / metabolism
  • Optic Nerve Injuries* / physiopathology
  • Optic Nerve* / metabolism
  • Phosphorylation
  • Retina* / drug effects
  • Retina* / metabolism
  • Retinal Ganglion Cells* / drug effects
  • Retinal Ganglion Cells* / metabolism
  • Semaphorin-3A* / genetics
  • Semaphorin-3A* / metabolism

Substances

  • collapsin response mediator protein-2
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Semaphorin-3A
  • Sema3a protein, mouse