Role of neurotrophin receptor TrkB in the maturation of rod photoreceptors and establishment of synaptic transmission to the inner retina.
Brain-derived neurotrophic factor (BDNF) acts through TrkB, a receptor with kinase activity, and mitigates light-induced apoptosis in adult mouse rod photoreceptors. To determine whether TrkB signaling is necessary for rod development and function, we examined the retinas of mice lacking all isoforms of the TrkB receptor. Rod migration and differentiation occur in the mutant retina, but proceed at slower rates than in wild-type mice. In postnatal day 16 (P16) mutants, rod outer segment dimensions and rhodopsin content are comparable with those of photoreceptors in P12 wild type (WT). Quantitative analyses of the photoreceptor component in the electroretinogram (ERG) indicate that the gain and kinetics of the rod phototransduction signal in dark-adapted P16 mutant and P12 WT retinas are similar. In contrast to P12 WT, however, the ERG in mutant mice entirely lacks a b-wave, indicating a failure of signal transmission in the retinal rod pathway. In the inner retina of mutant mice, although cells appear anatomically and immunohistochemically normal, they fail to respond to prolonged stroboscopic illumination with the normal expression of c-fos. Absence of the b-wave and failure of c-fos expression, in view of anatomically normal inner retinal cells, suggest that lack of TrkB signaling causes a defect in synaptic signaling between rods and inner retinal cells. Retinal pigment epithelial cells and cells in the inner retina, including Müller, amacrine, and retinal ganglion cells, express the TrkB receptor, but rod photoreceptors do not. Moreover, inner retinal cells respond to exogenous BDNF with c-fos expression and extracellular signal-regulated kinase phosphorylation. Thus, interactions of rods with TrkB-expressing cells must be required for normal rod development.
Rohrer
B
B
Howard Hughes Medical Institute, School of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
Korenbrot
J I
JI
LaVail
M M
MM
Reichardt
L F
LF
Xu
B
B
D000375:Aging / Q000502:physiology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D004596:Electroretinography; D007150:Immunohistochemistry; D008027:Light; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout / Q000235:genetics; D009154:Mutation / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000254:growth & development*; D012243:Rhodopsin / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D016760:Proto-Oncogene Proteins c-fos; D012243:Rhodopsin; D020813:Receptor, trkB