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Study On The Corneal Allogeneic Transplantation Immunological Tolerance And Immuno-suppression Induced By TGF-β1

Posted on:2003-10-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q HuFull Text:PDF
GTID:1104360065457057Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
Keratonosus is the main eye diseases that can lead to blind. Keratoplasty is the important vision restoration operation that can treat the corneal blind, and the important measure that can treat some chronic and stubborn keratopathies. Although keratoplasty has a high successful rate (the corneal allogeneic transplantation rejection rate is only 5-10% under the condition of avascular recipient beds), the rejection rate of the corneal allogeneic transplantation is higher than 50% under the condition of prevascularized recipient beds or second corneal transplantation. Therefore the corneal allograft rejection is still the main causes that can lead to corneal transplantation failure. The intensive study on the treatment and prevention of corneal allograft rejection will have very important meaning in order to increase the successful rate of the keratoplasty.The application with the immunodepressions is now the main methods to prevent and treat corneal allograft rejection after the keratoplasty. Although the application of immunodepressions can greatly increase the successful rate of the corneal transplantation and the survival rate of the corneal graft, there are still some cases that can not be healed, especially under the condition of the high-risk corneal transplantation in whichimmunodepression has little effectiveness. The immunodepressions now widely used are to depress the whole immunity system with the nonspecific way, the poison and side effect of itself also limits the its long-term and effective application. Therefore the specific immunological tolerance to induce corneal recipients to donors will be the more ideal method to prevent the corneal allograft rejection.In the allogeneic transplantation, the dendritic cells induce immune response by means of presenting allogeneic MHC antigen and expressing costimulator molecule such as CD80 and CD86 to activate recipient naive T cells. It is now recognized that DC can either cause the transplantation rejection, or induce the immunological tolerance, depending on the source of DC, its differentiation and maturity status. The mature DC can activate naive T cells to intermediate transplantation rejection. Immature DC can induce T cells non-responsiveness to cause the immunological tolerance because of the costimulator molecule expressive defects. The recent study has proved that the injection of the recipient mice with the immature DC before the operation can significantly prolong the mouse cardiac allograft survival.Transforming growth factor- 1 , (TGF- 1 ,) is strong immune depressive cytokine which can affect the proliferation and differentiation of hematopoietic progenitor cells (including DC), prevent the maturity of DC and induce allogeneic immunological tolerance. Therefore TGF- 3 j can induce the immunological tolerogen as tolerogenic factor. The recent study shows that TGF- 1 , can antagonize allograft rejection, and the application of TGF- P jto the allogeneic heart transplantation and pancreas islet cell transplantation model in the mice and rats can significantly prolong the allograft survival. This shows that TGF- 1 as an immunodepressive alsohas the potential to prolong the allograft survival.Therefore, this study will further study the possible mechanism that TGF- 1 ,can induce corneal allograft in order to prolong survival, based on the establishment of rat allogeneic corneal transplantation immunological tolerance model with the application of TGF- 3 ,. This study can provide the experimental basis to develop the study on allogeneic corneal transplantation immunological tolerance. At the same time, the preliminary clinical observation has been made, in which TGF- 3 , has been partially applied to the keratonosus such as the allograft rejection after the allogeneic keratoplasty, the mooren ulcer and herpes simplex stromal keratitis. The study mentioned above has not been reported in the references read.Part I Effects on rat bone marrow-deprived dendritic cell phenotype and immune stimulating activity produced by TGF- 1 ,...
Keywords/Search Tags:Transforming growth factor-β1, Penetrating keratoplasty, immunological tolerance, immuno-suppression
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