Sensitized heat shock protein 27 induces retinal ganglion cells apoptosis in rat glaucoma model

Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.

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Simvastatin promotes heat shock protein 27 expression and Akt activation in the rat retina and protects axotomized retinal ganglion cells in vivo

Neurobiology of Disease ◽

10.1016/j.nbd.2005.08.003 ◽

2006 ◽

Vol 21 (2) ◽

pp. 421-430 ◽

Cited By ~ 52

Author(s):

Alexandra Kretz ◽

Christian Schmeer ◽

Svetlana Tausch ◽

Stefan Isenmann

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Heat Shock Protein 27 ◽

Retinal Ganglion ◽

Rat Retina ◽

Akt Activation

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Heat Shock Protein 27 Delays Ca2+-Induced Cell Death in a Caspase-Dependent and -Independent Manner in Rat Retinal Ganglion Cells

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.04-0042 ◽

2005 ◽

Vol 46 (3) ◽

pp. 1085 ◽

Cited By ~ 38

Author(s):

N. Andrew Whitlock ◽

Kristie Lindsey ◽

Neeraj Agarwal ◽

Craig E. Crosson ◽

Jian-Xing Ma

Keyword(s):

Cell Death ◽

Heat Shock ◽

Heat Shock Protein ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Heat Shock Protein 27 ◽

Retinal Ganglion ◽

Independent Manner

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Heat shock protein 90 in retinal ganglion cells: Association with axonally transported proteins

Visual Neuroscience ◽

10.1017/s0952523801183094 ◽

2001 ◽

Vol 18 (3) ◽

pp. 429-436 ◽

Cited By ~ 14

Author(s):

STEVEN L. BERNSTEIN ◽

PAUL RUSSELL ◽

PAUL WONG ◽

RITA FISHELEVICH ◽

LOIS E.H. SMITH

Keyword(s):

Optic Nerve ◽

Heat Shock ◽

Heat Shock Protein ◽

Map Kinase ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Heat Shock Protein 90 ◽

Kinase Assay ◽

Neurotrophin Receptor ◽

Retinal Ganglion

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.

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