NEUROIMMUNOMODULATION WITHIN THE EYE

Summary

Principal Investigator: Andrew W Taylor
Affiliation: Boston University
Country: USA
Abstract: The eye normally possesses a unique physiological adaptation that regionally modifies the expression of immunity. This physiological adaptation is part of ocular immune privilege. The physiological role of immune privilege is to impart upon the eye immune protection that avoids the destructive side effects of immunogenic inflammation. Immunogenic inflammation associated with delayed hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Consequently, immune protection within the eye involves a selective deficiency of delayed type hypersensitivity T-cells. To control immunogenic inflammation, the cells and neurons within the ocular microenvironment produce immunomodulating factors that regionally suppress T-cell inflammatory-mediating activities. A biochemical examination of aqueous humor has shown that some of its immunosuppressive activity is associated with alpha-melanocyte stimulating hormone (alpha-MSH). Through alpha-MSH, aqueous humor suppresses IFN-gamma production but promotes proliferation of TGF-beta-producing effector T cells. These effector T cells act as regulatory T cells in that they can suppress immunogenic inflammation mediated by other inflammatory T cells. Moreover, if such regulatory T cells respond specifically to ocular autoantigens, they can suppress the severity and incidence of autoimmune retinitis. The induction of regulatory T cells is a result of alpha-MSH influencing the ability of antigen presenting cells (APC) to activate T cells and directly on T cells responding to presented antigen. It is our plan to characterize the effects of alpha-MSH on the mechanisms of T cell activation. We will also test the possibility that an injection of either alpha-MSH itself or alpha-MSH-induced regulatory T cells can suppress the incidence and severity of ocular autoimmune disease. The results of this project will allow us to understand the molecular and cellular features of immunity within the normal eye. By understanding the activity of intraocular immunomodulatory factors, such as alpha-MSH, it will be possible to induce an immune response that promotes the elimination of pathogens and tumors without the blinding consequences of immunogenic inflammation, that prevents or cures autoimmune diseases of the eye, and that promotes success of corneal, retinal and other tissue transplants.
Funding Period: 1995-04-01 - 2006-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Inducible immune regulation following autoimmune disease in the immune-privileged eye
    Nobuyoshi Kitaichi
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Leukoc Biol 77:496-502. 2005
  2. ncbi Review of the activation of TGF-beta in immunity
    Andrew W Taylor
    Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA
    J Leukoc Biol 85:29-33. 2009
  3. ncbi Local treatment with alpha-melanocyte stimulating hormone reduces corneal allorejection
    Pedram Hamrah
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    Transplantation 88:180-7. 2009
  4. ncbi The immune privileged retina mediates an alternative activation of J774A.1 cells
    Chun H Lau
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02116, USA
    Ocul Immunol Inflamm 17:380-9. 2009

Scientific Experts

  • A W Taylor
  • Pedram Hamrah
  • Chun H Lau
  • Nobuyoshi Kitaichi
  • Zdenka Haskova
  • M Reza Dana
  • Bruce R Ksander
  • Qiang Zhang
  • Kenichi Namba

Detail Information

Publications4

  1. ncbi Inducible immune regulation following autoimmune disease in the immune-privileged eye
    Nobuyoshi Kitaichi
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    J Leukoc Biol 77:496-502. 2005
    ....
  2. ncbi Review of the activation of TGF-beta in immunity
    Andrew W Taylor
    Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA
    J Leukoc Biol 85:29-33. 2009
    ..A mechanistic understanding of the process activating TGF-beta can lead to regulating multiple biological systems by enhancing or inhibiting TGF-beta activation...
  3. ncbi Local treatment with alpha-melanocyte stimulating hormone reduces corneal allorejection
    Pedram Hamrah
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
    Transplantation 88:180-7. 2009
    ..The purpose of this study was to determine the role of local therapy with alpha-MSH on corneal allograft survival, and the mechanisms by which it may influence graft outcome...
  4. ncbi The immune privileged retina mediates an alternative activation of J774A.1 cells
    Chun H Lau
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02116, USA
    Ocul Immunol Inflamm 17:380-9. 2009
    ..We further assessed the possibility that the RPE is alternatively activating macrophages...