Neurotrophin receptor TrkB activation is not required for the postnatal survival of retinal ganglion cells in vivo

During early postnatal development, apoptosis of retinal ganglion cells (RG Cs) is regulated by target contact with the optic tectum. The neurotrophins BDNF and NT-4, but not NGF, prevent the apoptosis of retinal ganglion cell s that is otherwise observed after target ablation or axotomy. Thus recepto rs activated by BDNF and NT-4 are candidates to mediate the early postnatal survival of RGCs. BDNF and NT-4, but not NGF, bind to all isoforms of the receptor TrkB, whether or not they contain a tyrosine kinase domain. To exa mine the roles of TrkB receptor isoforms in early postnatal survival, we co mpared RGC numbers in wild-type mice to those in a mutant lacking all isofo rms of TrkB. Surprisingly, no reduction in RGCs was observed in the mutant at postnatal day 16, the latest age at which these animals are consistently viable, so TrkB signaling is not essential for target-dependent survival o f these cells. In wild-type mice, RGCs also are lost gradually during adult hood, possibly due to oxidative stress. To determine whether TrkB signaling regulates this phase of RGC degeneration, RGC numbers were examined in a v iable mutant of TrkB that expresses only about 25% the normal level of TrkB receptor kinase. Compared to controls, approximately 20% of the RGC were l ost in mutant 3-month-old-animals. Thus, TrkB signaling is not required for survival of RGCs during the period of target-dependent survival, but does appear to reduce degeneration of RGCs in adult animals. (C) 2001 Academic P ress.