May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
T Cell-Mediated Autoimmune Component of Glaucomatous Neurodegeneration in a Chronic Pressure-Induced Rat Model of Glaucoma
Author Affiliations & Notes
  • G. Tezel
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • X. Yang
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • C. Luo
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • Y. Peng
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • D. Sun
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • H. J. Kaplan
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, Kentucky
  • Footnotes
    Commercial Relationships  G. Tezel, None; X. Yang, None; C. Luo, None; Y. Peng, None; D. Sun, None; H.J. Kaplan, None.
  • Footnotes
    Support  NEI grants, 2R01 EY013813, 1R01 EY017131, and R24 EY015636, and RPB
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3699. doi:https://doi.org/
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    • Get Citation

      G. Tezel, X. Yang, C. Luo, Y. Peng, D. Sun, H. J. Kaplan; T Cell-Mediated Autoimmune Component of Glaucomatous Neurodegeneration in a Chronic Pressure-Induced Rat Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3699. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Growing evidence supports an aberrant activation of the immune system in glaucoma, in which glial cells activated in response to glaucomatous stress and/or injury serve as antigen presenting cells. In this study, we aimed to determine whether T cells are activated in ocular hypertensive rats, and if so, whether the adoptive transfer of T cells elicits any neurodegenerative injury in naïve animals.

Methods: : IOP elevation was induced in rats by hypertonic saline injections into episcleral veins. During an ocular hypertensive period of up to 12 weeks, T cells were isolated from regional lymph nodes and the spleen. To determine T cell response to retinal proteins, T cell proliferation was determined by [3H]-thymidine incorporation, and cytokine secretion was measured using enzyme-linked immunosorbent assay. Autoantibody profiles were also obtained through western blot analysis of serum samples. Following a 2-day in vitro stimulation of T cells with retinal antigens, activated T cell blasts were isolated and injected into naïve animals as well as animals with ocular hypertension. At different time points (post-injection day 1, 3, 5, 10), glial reactivity was determined by CD11b and GFAP immunolabeling, and T cell invasion was determined by CD45 immunolabeling of the retina and optic nerve sections. In addition, neuronal damage was evaluated by counting retinal ganglion cells and their axons.

Results: : T cells isolated from ocular hypertensive animals exhibited an approximately three-fold stimulated response to retinal proteins compared with normotensive controls, which was correlated with elevated IOP and neuronal damage. Sera from ocular hypertensive animals also exhibited increased immunoreactivity to retinal proteins. Retinas and optic nerves obtained from T cell-injected animals exhibited microglial activation and a transient T cell invasion. Although there was no detectable neuronal damage in T cell-injected naïve animals, T cell-injected ocular hypertensive rats exhibited more advanced damage compared with un-injected ocular hypertensive animals.

Conclusions: : This study revealed that the immune system is activated in ocular hypertensive rats and that the stimulated T cell response may lead to secondary autoimmune injury contributing to the progression of neurodegeneration. Continuing studies should clarify mechanisms of immune dysregulation in glaucoma, identify organ-specific antigens, and provide immunomodulatory treatment strategies for neuroprotection.

Keywords: optic nerve • autoimmune disease • neuroprotection 
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