Expression of trkA, trkB, and trkC in injured and regenerating retinal ganglion cells of adult rats

Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1954-64.

Abstract

Purpose: To investigate changes in percentage of tyrosine kinase (trk)A-, trkB-, and trkC-immunopositive ((+)) retinal ganglion cells (RGCs) at various times after optic nerve (ON) axotomy; the proportion of RGCs regenerating axons into peripheral nerve (PN) grafts that are trkA(+), trkB(+), and trkC(+); whether intravitreal PN-ON implants affect trk immunoreactivity; and the levels of trk mRNAs in ON-injured retinas.

Methods: The ON was transected intraorbitally. Proportions of trkA(+), trkB(+), and trkC(+) RGCs and levels of trk mRNAs were studied by using immunocytochemistry and Northern blot methods, respectively, in injured and RGC-regenerating retinas.

Results: In normal retinas, only small numbers of trkB(+) and trkC(+), but not trkA(+), RGCs were seen. The optic fiber layer was intensively immunolabeled with trkB. After ON injury, the proportions of trkA(+), trkB(+), and trkC(+) RGCs rapidly increased and reached their peaks by 3 to 5 days. During the next 3 weeks, the proportion of trkA(+) or trkB(+) RGCs gradually decreased, but the proportion of trkC(+) RGCs remained high. Intravitreal implants of PN+ON segments transiently but significantly suppressed injury-induced increases in all these trk(+) RGC proportions for approximately 5 days. In contrast, 3 days after ON injury, quantitative retinal expression of trkA mRNA, and to a lesser extent trkC mRNA, was downregulated, whereas trkB mRNA expression remained unaffected. Higher proportions of trkA(+) and trkB(+) RGCs and higher levels of all trk mRNAs were seen in regenerating RGCs and retinas, respectively.

Conclusions: This study provides a kinetic analysis of expression of trk in RGCs and retinas after ON injury and during regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axotomy
  • Blotting, Northern
  • Cell Survival
  • DNA Probes
  • Down-Regulation
  • Fluorescent Antibody Technique, Indirect
  • Nerve Regeneration / physiology*
  • Optic Nerve / physiology*
  • Optic Nerve Injuries / enzymology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkA / genetics*
  • Receptor, trkA / metabolism
  • Receptor, trkB / genetics*
  • Receptor, trkB / metabolism
  • Receptor, trkC / genetics*
  • Receptor, trkC / metabolism
  • Retina / metabolism
  • Retinal Ganglion Cells / enzymology*
  • Time Factors

Substances

  • DNA Probes
  • RNA, Messenger
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC