Induced Autoimmunity to Heat Shock Proteins Elicits Glaucomatous Loss of Retinal Ganglion Cell Neurons via Activated T-Cell-Derived Fas-Ligand
| Autor: | Rebecca M. Sappington, Junjie Yang, Guanghua Peng, Gülgün Tezel, Martin B. Wax, Neeraj Agarwal, Rajkumar V. Patil, David J. Calkins |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Retinal Ganglion Cells Retinal degeneration Fas Ligand Protein genetic structures T-Lymphocytes Glaucoma Apoptosis Autoimmunity Biology Lymphocyte Activation Retinal ganglion Article Cell Line Rats Sprague-Dawley Autoimmune Diseases of the Nervous System Heat shock protein medicine Animals fas Receptor Heat-Shock Proteins Intraocular Pressure Autoantibodies Retina General Neuroscience Retinal Degeneration medicine.disease eye diseases Rats Cell biology medicine.anatomical_structure Animals Newborn Retinal ganglion cell Rats Inbred Lew Nerve Degeneration Immunology Optic nerve HSP60 Microglia sense organs |
| Zdroj: | The Journal of Neuroscience. 28:12085-12096 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3200-08.2008 |
| Popis: | Glaucomatous optic neuropathy causes blindness through the degeneration of retinal ganglion cells (RGCs) and their axons, which comprise the optic nerve. Glaucoma traditionally is associated with elevated intraocular pressure, but often occurs or may progress with intraocular pressure in the normal range. Like other diseases of the CNS, a subset of glaucoma has been proposed to involve an autoimmune component to help explain the loss of RGCs in the absence of elevated intraocular pressure. One hypothesis involves heat shock proteins (HSPs), because increased serum levels of HSP autoantibodies are prominent in some glaucoma patients with normal pressures. In the first direct support of this hypothesis, we found that HSP27 and HSP60 immunization in the Lewis rat induced RGC degeneration and axon loss 1–4 months laterin vivoin a pattern with similarities to human glaucoma, including topographic specificity of cell loss. Infiltration of increased numbers of T-cells in the retina occurred much earlier, 14–21 d after HSP immunization, and appeared to be transient.In vitrostudies found that T-cells activated by HSP immunization induced RGC apoptosis via the release of the inflammatory cytokine FasL, whereas HSP immunization induced activation of microglia cells and upregulation of the FasL receptor in RGCs. In summary, our results suggest that RGC degeneration in glaucoma for selected individuals likely involves failed immunoregulation of the T-cell-RGC axis and is thus a disturbance of both proapoptotic and protective pathways. |
| Databáze: | OpenAIRE |
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