| Background: Corneal transplantation has a high success rate, which is usually attributed to the avascular nature of cornea that confers a degree of immune privilege, but the corneal transplant rejection and angiogenesis is the major reason of the failure for corneal transplantation. Cytokines is a signal transmission molecule that play a critical role in adjusting inflammation and immune response. Interaction between cytokines and their forms a complex and integrity network that control physiological and pathological process of cells and tissues. One hand, some cytokines and their receptors adjust the immuneologic rejection of the tissue transplantation; on the other hand, it's advantageous to induce immunologic tolerance. Therefore, in-depth research on cytokines is useful in studying the immunopathologic process of rejection and pave new ways for probe the corneal graft rejection.The antigen-presenting cells (APCs) such as Langerhans cells (LC), an epithelial form of dendritic cells (DCs), in corneal tissue is critical for generation of immunological rejection. In normal condition, the central portion of the corneal epithelium is typically devoid of LC. The absence of la+Langerhans cells in the central cornea indicates the immunologic privilege that is characteristic of corneal allografts. Corneal LC is capable of migrating from the periphery to the central regions of the cornea following grafts rejection. Results from the experiments pointed out that the presence of donor-derived LC increased the incidence of corneal allograft rejection. Therefore, The consistent absence of LC in that portion of the cornea normally used for corneal transplantation offers an unusual opportunity, in the elicitation of alloimmune responses and allograft rejection. It was reported recently that Interluekin-1(IL-1) is able to induce LC from the periphery to the central regions of the cornea. Released by mononuclear phagocyte, DL-1 is an important multifunctional cytokine that has a wide range of activities, including the critical mediation of the acute phase response,chemotaxis and activation of inflammatory and antigen-presenting cells, up-regulation of adhesion molecules on cells, and stimulation of neovascularization. Importantly, IL-1 plays key role in LC migration which hosts allosensitization in the setting of corneal transplantation. IL-1 receptor antagonist (IL-1ra) is a recently characterized molecule that acts as a pure antagonist of biologically active IL-1. II-Ira blocks cellular responses to IL-1 by binding almost irreversibly to the IL-1 receptor without triggering signal transduction. The animal experiments indicated that IL-lra can markely prolong the survival time of corneal allografts by inhibiting graft rejection, and prevent vascular growth of corneal allografts, although the mechanism is still unclear.Vascular endothelial growth factor (VEGF) is unique polypeptide agent to effect intima. VEGF can accelerate the growth of corneal neovasculariza--tion. The experiment shows that IL-1 could markedly accelerate the expression of VEGF. The expressions of VEGF are in direct proportion to the growth of corneal neovascularization (CNV). Tumor necrosis factor- a (TNF-a ) is a important agent to attend inflammatory reaction and immune response. TNF- a is able to induce the expression of IL-1 antigen and accelerate the growth of CNV. Here we perform this experiment to further identify the relationship among interleukin-1, IL-lra, and cytokines during the acute immune rejection in experiment penetrating keratoplasty in rat modle. Objectives:1. To investigate LC distribution and the expressions of cytokines (VEGF, TNF- a ) on normal corneas in rat. And to analyze their roles in the corneal allograft rejection.2. To investigate the change of LC distribution and the expressions of cytokines (VEGF, TNF- a ) on the corneal allografts in rat, and their relationship with penetrating keratoplasty rejection.3. To study comparatively the immunosuppressive effect of II-Ira and CsAon the rejection duri...
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