Copolymer-1 immunization reduces damage in retinal ganglion cells under high intraocular pressure through altering the expression of retinal neurotrophins

J Ocul Pharmacol Ther. 2010 Feb;26(1):11-9. doi: 10.1089/jop.2009.0037.

Abstract

Purpose: To evaluate expression changes in retina neurotrophic factors (NTs) in glaucomatous rats with copolymer-1 (COP-1) immunization.

Methods: Three episcleral veins in rat eyes were cauterized to produce chronic high intraocular pressure (IOP). Qualified rats were divided into 3 groups: glaucoma group, COP-1 immunization group, and PBS control group. Using immunohistochemistry and RT-PCR, we compared the expression of retinal NTs in these 3 groups.

Results: NGF, BDNF, and NT-4 expression increased to different degrees and the levels of their RNAs had transient increases under elevated IOP, but there were no statistical differences with respect to the RNAs of interest in the COP-1 immunization group compared with the 2 control groups. Expression of NT-3 appeared earlier and stronger in the rats immunized with COP-1 than in rats with glaucoma. Moreover, the expression of the COP-1 receptor, TrkC, increased accordingly.

Conclusions: COP-1 immunization might increase NT-3 expression by some unknown mechanism in high IOP rats and the change may be related to COP-1 therapeutic intervention.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • CCN Intercellular Signaling Proteins
  • Cell Count
  • Female
  • Glaucoma / immunology*
  • Glaucoma / metabolism*
  • Glaucoma / pathology
  • Glaucoma / physiopathology
  • Immunization*
  • Immunohistochemistry / methods
  • Intraocular Pressure
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Neurotrophin 3 / genetics
  • Neurotrophin 3 / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, trkC / genetics
  • Receptor, trkC / metabolism
  • Receptors, Nerve Growth Factor
  • Repressor Proteins / immunology*
  • Retinal Ganglion Cells / immunology
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Staining and Labeling

Substances

  • Brain-Derived Neurotrophic Factor
  • CCN Intercellular Signaling Proteins
  • CCN5 protein, rat
  • Nerve Growth Factors
  • Neurotrophin 3
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • Repressor Proteins
  • Nerve Growth Factor
  • Receptor, trkC
  • neurotrophin 4