We have examined the role of neurotrophins in promoting
survival of mammalian rod bipolar cells (RBC) in culture.
Retinas taken from 8- to 10-day-old Long-Evans rats were
dissociated and cultured in media supplemented with either
nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived
neurotrophic factor (BDNF), ciliary neurotrophic factor
(CNTF), or basic fibroblast growth factor (FGF-2). Survival
was measured by the number of cells that were immunoreactive
for α-, β-, γ-PKC, a bipolar cell-specific
marker. Compared to untreated cultures, CNTF had no effect
on RBC survival, while NGF and NT-3 increased survival
only slightly. BDNF, however, increased survival by approximately
300%. Similar results were obtained with FGF-2. Both nerve
growth factor (NGF) and an antibody (anti-REX) which interferes
with binding to the 75-kD low-affinity neurotrophin receptor
(p75NTR) eliminated BDNF-promoted survival,
but had no effect on FGF-2-mediated survival. Interestingly,
p75NTR was expressed by retinal glia (Müller
cells), but not by the bipolar cells themselves, providing
for the possibility that BDNF might induce Müller
cells to produce a secondary factor, perhaps FGF-2, which
directly rescues RBCs. In support of this hypothesis, an
antibody that neutralizes FGF-2 attenuated the trophic
effects of BDNF, and dramatically reduced survival in cultures
with no added growth factors, indicating that there may
be an endogenous source of FGF-2 that promotes survival
of RBCs in culture. We suggest that BDNF increases production
or release of FGF-2 by binding to p75NTR on
Müller cells.
Nerve growth factor promotes the proliferation of Müller cells co-cultured with internal limiting membrane by regulating cell cycle via Trk-A/PI3K/Akt pathway
