CORNEAL WOUND HEALING, REJECTION, IMMUNOTHERAPY

Henry Ford Health System, Detroit MI

Investigators

Linked publications & trials

Abstract

The Candidate will be involved in a comprehensive didactic and laboratory research program, including course work in immunology, cell biology, and molecular biology, as well as seminars, workshops, and regularly scheduled laboratory meetings focused on cellular and molecular immunology. The intensive research program for the Candidate involves the study of wound healing and wound apposition in corneal allografts, the characterization of the initiation of the immune response to corneal allografts, and the investigation of single and multiple drug therapies to prevent corneal allograft rejection. The confocal microscope is a newly developed clinical and research tool that will allow studies of graft rejection to be carried out largely in vivo, first in animal models and then in human eyes. This unique approach will, for the first time, be able to document the interaction of leukocytes and endothelial cells. Our previous confocal studies show that leukocytes can be seen in the rabbit stroma and that the human endothelium can be visualized even through an edematous cornea. These two observations suggest that this methodology will yield a much more complete understanding of the development of graft rejection and may eventually be useful in establishing guidelines for clinical diagnosis. Specific Aim 1 involves obtaining the fundamental basic science and research expertise needed as a basis for a career as an academic scientist, teacher, and clinician. Specific Aim 2a focuses on the cellular events involved in corneal allograft transplantation and rejection. The time course and cell types involved in these processes will be characterized by slit lamp examination, immunocytologic staining, and confocal and electron microscopy. Using available fluorochrome-tagged antibodies, it will be possible to identify lymphocyte subsets as they migrate into corneal allografts and mediate graft cell death. Specific Aim 2b is designed to compare efficacy and determine specific cytocellular differences in inhibition using topical corticosteroids and one the newer generation of immunosuppressive drugs such as Cyclosporine A, FK-506, and/or Rapamycin. In later phases, combination drug therapy will be tested for possible synergistic effects on cornea graft survival. The clinical confocal microscope will be used to perform early diagnosis of immune graft reactions. The prompt treatment of such reactions with effective immunosuppressive drug regimens will represent a major advance in the clinical management of post-keratoplasty immune graft reactions. This comprehensive program of didactic study seminar presentation, and laboratory investigation will allow the Candidate to earn a Ph.D. in Anatomy and will ensure that he is a capable, well trained, independent investigator upon completing the program.