Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal retina and following optic nerve crush in adult rats

Hao Chen, Arthur J. Weber

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) is a well-known retinal neuroprotectant, but its effectiveness is limited; higher doses do not yield increased cell survival, multiple applications are not additive, and long-term delivery does not reverse, ganglion cell death. These limitations might reflect either injury- or BDNF-induced retinal changes in TrkB, the high affinity tyrosine kinase receptor used by BDNF. Retinal levels of TrkB protein and mRNA were measured in rats following intravitreal application of BDNF alone, optic nerve crush alone, and both. Full-length receptor protein levels (TrkB.FL) were determined by Western blot analysis and mRNA (trkB.FL) levels were measured using RNAse protection assay (RPA). BDNF alone produced a rapid and prolonged decrease in normal retina TrkB.FL. Nerve crush also resulted in decreased TrkB.FL, but the reduction was not apparent before 2-week post-crush. BDNF applied at the time of the crush yielded reductions in TrkB.FL similar to that of BDNF alone. With respect to TrkB mRNA levels, injection of BDNF into normal eyes and optic nerve crush alone showed bell-shaped patterns of change: ∼50% below normal at 24-h post-procedure, ∼50% above normal at 3 days, normal at 7 days, and ∼50% below normal at 2-week post-procedure. When BDNF and nerve crush were combined, trkB-FL levels reached 90% of normal 1-week post-crush/injection. The data suggest that the limitation of BDNF in promoting ganglion cell survival following optic nerve injury results, in part, due to drug-induced down-regulation of the full-length TrkB receptor needed to activate intracellular pathways.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalBrain Research
Volume1011
Issue number1
DOIs
StatePublished - Jun 11 2004

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Nerve Crush
Brain-Derived Neurotrophic Factor
Optic Nerve
Retina
Messenger RNA
Proteins
Ganglia
Cell Survival
trkB Receptor
Optic Nerve Injuries
Injections
Receptor Protein-Tyrosine Kinases
Neuroprotective Agents
Cell Death
Down-Regulation
Western Blotting

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal retina and following optic nerve crush in adult rats. / Chen, Hao; Weber, Arthur J.

In: Brain Research, Vol. 1011, No. 1, 11.06.2004, p. 99-106.

Research output: Contribution to journalArticle

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