Abstract
We investigated the effects of endogenous neurotrophin signaling on the death-survival of immature retinal ganglion cells (RGCs) in vivo. Null mutation of brain-derived neurotrophic factor [(BDNF) alone or in combination with neurotrophin 4 (NT4)] increases the peak rate of developmental RGC death as compared with normal. Null mutation of NT4 alone is ineffective. Null mutation of the full-length trkB (trkBFL) receptor catalytic domain produces a dose-dependent increase in the peak RGC death rate that is negatively correlated with retinal levels of trkBFL protein and phosphorylated (activated) trkBFL. Depletion of target-derived trkB ligands by injection of trkB-Fc fusion protein into the superior colliculus increases the peak rate of RGC death compared with trkA-Fc-treated and normal animals. Adult trkBFL+/- mice have a normal number of RGCs, despite an elevated peak death rate of immature RGCs. Thus, target-derived BDNF modulates the dynamics of developmental RGC death through trkBFL activation, but BDNF/trkB-independent mechanisms determine the final number of RGCs.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Brain-Derived Neurotrophic Factor / genetics
-
Brain-Derived Neurotrophic Factor / metabolism
-
Cell Count
-
Cell Death / drug effects
-
Cell Death / genetics
-
Cell Survival / drug effects
-
Cell Survival / genetics
-
Cricetinae
-
Immunoglobulin Fc Fragments / genetics
-
Injections, Spinal
-
Ligands
-
Mesocricetus
-
Mice
-
Mice, Mutant Strains
-
Nerve Growth Factors / genetics
-
Nerve Growth Factors / metabolism
-
Receptor, trkB / genetics
-
Receptor, trkB / metabolism*
-
Recombinant Fusion Proteins / administration & dosage
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Retina / cytology
-
Retina / growth & development
-
Retina / metabolism
-
Retinal Ganglion Cells / cytology*
-
Retinal Ganglion Cells / drug effects
-
Retinal Ganglion Cells / metabolism*
-
Signal Transduction / drug effects
-
Signal Transduction / physiology*
-
Superior Colliculi / drug effects
Substances
-
Brain-Derived Neurotrophic Factor
-
Immunoglobulin Fc Fragments
-
Ligands
-
Nerve Growth Factors
-
Recombinant Fusion Proteins
-
Receptor, trkB
-
neurotrophin 4