The mRNAs for heat shock protein 90 (HSP90) are found at highest
levels (differentially expressed) in the primate retinal fovea,
the region of highest visual acuity, compared to the peripheral
retina. HSP90 expression and retinal associations were analyzed
by immuno-localization, in situ hybridization, and
western analysis. Retinal ganglion cells (RGCs) express much
of the HSP90 mRNA present in the primate retinal fovea. A large
fraction of RGC synthesized HSP90 is apparently present in the
axonal compartment. To identify the role of HSP90 protein in
the optic nerve and retina, co-immunoprecipitation experiments
were performed, using antibodies specific for HSP90 isoforms.
The immunoprecipitates were analyzed for neurotrophin receptor
and ligand activities, and MAP kinase activity. MAP kinase assay
was used to determine the activation state of MAP kinase associated
with HSP90. HSP90 proteins selectively associate with the inactive
form of full-length tyrosine kinase growth factor receptor trkB,
suggesting utilization during anterograde axonal transport.
Activated MAP kinase, associated with the trk downstream signaling
cascade, was found to co-immunoprecipitate with optic nerve
HSP90, suggesting that HSP90 may be utilized in retrograde
transport of the secondary messengers associated with neurotrophin
signaling. HSP90 can thus be hypothesized to play a role in
bidirectional RGC axonal protein transport.
Heat shock protein 72 confers protection in retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model
