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Corneal Transplantation (corneal + transplantation)
Selected Abstracts,Chimeric' Grafts Assembled from Multiple Allodisparate Donors Enjoy Enhanced Transplant SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009D. R. Saban Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium,which shares the same alloantigens,is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such ,chimeric' allografts consisted of a C3H/He (H-2k) corneal epithelium over a C57BL/6 (H-2b) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2d) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4+ interferon [IFN]-,+) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds. [source] 3135: Modulation of apoptotic signaling pathways to promote survival of endothelial cells by gene therapyACTA OPHTHALMOLOGICA, Issue 2010T FUCHSLUGER Purpose Corneal transplantation is the most common transplantation worldwide. Surgeons and eye banks face major problems: (1) shortage of tissue in aging populations, (2) loss of high-quality tissue due to cell loss during storage, (3) graft failure. It has been demonstrated that EC loss is mediated by the cells' intrinsic death machinery resulting in apoptosis. Identification of survival strategies could raise the availability of tissue, with a significant impact on transplantation by lowering graft rejection rate. The purpose of this study different apoptotic pathways and to determine the protective effect of the anti-apoptotic proteins bcl-xL and p35. Methods Intrinsic (mitochondria-mediated) and extrinsic (ligand-mediated) apoptotic pathways were selectively activated to provoke apoptosis of murine and human corneal endothelial cells suspensions and corneas. Gene transfer of bcl-xL or p35 was accomplished, survival of EC was determined by flow cytometry and laser scanning microscopy. Results Interestingly, we were able to determine distinct differences in cell survival enhancement depending on the type of overexpressed protein. Whereas uninfected controls showed significant EC death, gene-therapeutically treated EC demonstrated significantly increased cell survival. We will present data on the efficacy of certain anti-apoptotic proteins in select pathways. Conclusion Exploring inhibitory strategies of EC death can lead to clinically relevant survival strategies with significant impact on corneal grafting. [source] History of and necessity for KProsACTA OPHTHALMOLOGICA, Issue 2009C LIU The history of keratoprostheses goes back over 200 years. There was a resurgence in interest in the second half of the twentieth century as it was recognised that keratoplasty could not solve all types of corneal blindness. Many devices have been described but few have survived. Corneal transplantation is complicated by graft rejection and astigmatism. There is also a problem with adequate supply, and there is a risk of transmission of infection. There is a desire for an artificial cornea which surpasses cadaveric transplantation. There is much ongoing work, but the majority of clinical work on keratoprostheses are for corneal blindness not amenable to cadaveric grafts. These can be separated into two main groups. The wet blinking eye which have had multiple graft failures, and the dry eye with a keratinised ocular surface which may also have a deficiency in lid cover. The approaches to these are quite different. [source] The taming of the shrew?ACTA OPHTHALMOLOGICA, Issue 5 2009The immunology of corneal transplantation Abstract. Corneal transplantation, first reported a century ago, is the oldest and most frequent form of solid tissue transplantation. Although keratoplasty is also considered as the most successful transplant procedure, several studies indicate that the long term survival of corneal grafts is even lower than that of transplanted parenchymatous organs. Despite the immune privilege enjoyed by the cornea and anterior segment of the eye, immunologic graft rejection is a major limitation to corneal transplantation. This review gives an update on corneal immunobiology and the mechanisms of corneal graft rejection, focusing on antigen presentation, as well as on the molecular and cellular mediators of this particular immune response. [source] Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2006Abstract Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-, and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts. [source] Decay Accelerating Factor is Essential for Successful Corneal EngraftmentAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010A. Esposito In contrast to immune restrictions that pertain for solid organ transplants, the tolerogenic milieu of the eye permits successful corneal transplantation without systemic immunosuppression, even across a fully MHC disparate barrier. Here we show that recipient and donor expression of decay accelerating factor (DAF or CD55), a cell surface C3/C5 convertase regulator recently shown to modulate T-cell responses, is essential to sustain successful corneal engraftment. Whereas wild-type (WT) corneas transplanted into multiple minor histocompatibility antigen (mH), or HY disparate WT recipients were accepted, DAF's absence on either the donor cornea or in the recipient bed induced rapid rejection. Donor or recipient DAF deficiency led to expansion of donor-reactive IFN-, producing CD4+ and CD8+ T cells, as well as inhibited antigen-induced IL-10 and TGF-,, together demonstrating that DAF deficiency precludes immune tolerance. In addition to demonstrating a requisite role for DAF in conferring ocular immune privilege, these results raise the possibility that augmenting DAF levels on donor corneal endothelium and/or the recipient bed could have therapeutic value for transplants that clinically are at high risk for rejection. [source] Immune responses to gene therapy vectors in the context of corneal transplantationACTA OPHTHALMOLOGICA, Issue 2009T RITTER Purpose The genetic engineering of grafts or cells prior to transplantation is an attractive approach to protect the graft from allogeneic rejection. Virus vector-based gene therapy is a promising method for successful ex-vivo gene transfer however, the induction of an immune response against gene-modified tissues raises concern. Methods Different virus families (Adenovirus, Retrovirus, Adeno-associated virus, Herpesvirus) have been studied as gene therapy vehicles for the delivery of therapeutic molecules. Moreover, different serotypes or envelope proteins have been used to modulate transduction efficiencies of target cells or to evade pre-existing immunity. Results Here we review gene therapeutic applications using viral vectors in the context of cornea transplantation. Both local and systemic expression of immunomodulatory molecules have led to the prevention of corneal graft rejection. However, different results have been obtained with regard to the induction of immune responses after local or systemic expression of the gene therapy vector. Not surprisingly over-expression of anti-inflammatory molecules not only modulated allograft rejection but also influenced the immune response against the viral vector and virally transduced cells. Conclusion Recent clinical trials indicate that the application of viral vectors in ophthalmology is promising however, the generation of immune responses against the viral vector or virally transduced cells are still a serious obstacle for a broader application of gene therapy. Supported by Deutsche Forschungsgemeinschaft (DFG Pl 150/14-1 and Ri 764/10-1) and Science Foundation of Ireland (SFI 06/RFP/BIC056 and SFI 07/IN.1/B925) [source] Gene therapy for corneal transplantationACTA OPHTHALMOLOGICA, Issue 2009U PLEYER [source] Gene therapy: can we prevent/modulate apoptosis in EC?ACTA OPHTHALMOLOGICA, Issue 2009T FUCHSLUGER Purpose Regardless of the inciting cause, CEC loss is a common denominator of corneal graft failure. CEC loss during storage results in significant loss of suitable tissue for grafting, CEC loss after transplantation is a major cause of graft failure. The purpose of this study is to investigate the role of apoptosis in CEC in order to prevent CEC loss during storage. Methods Gene transfer of Lenti-Bcl-xL or ,p35 was accomplished in human donor corneas, primary cultured CEC and an immortalized CEC line and compared to untreated controls. Cell death (apoptosis) was induced by Actinomycin or Etoposide (external vs. internal apoptotic pathway, respectively). In addition, CEC loss during preservation was studied both during Optisol GS (4C) and organ culture storage (37C, Biochrome Medium I). Both storage media were diluted with PBS to promote cell loss. CEC were enumerated, apoptosis was detected by TUNEL staining and confocal microscopy. Results The percentage of TUNEL-positive CEC provoked by the apoptotic inducers was significantly reduced relative to controls. Transfected corneas preserved an almost intact endothelial monolayer while controls nearly entirely lost vital CEC. During long-term storage experiments at 4C and at 37C, CEC counts in corneas expressing anti-apoptotic genes remained significantly higher compared to the controls. Conclusion Protection of CEC by anti-apoptotic genes appears to be an effective method to reduce CEC loss during storage. The application of this technique could increase the amount of high quality grafts in eye banking and further reduce graft failure following corneal transplantation, and is be of specific interest as to precut corneas and DSAEK procedures. [source] The Boston keratoprosthesis in autoimmune diseaseACTA OPHTHALMOLOGICA, Issue 2009J CHODOSH Purpose Patients with corneal blindness due to mucous membrane pemphigoid and Stevens Johnson syndrome who undergo corneal transplantation carry a poor prognosis for visual recovery. The Boston keratoprosthesis has been demonstrated to provide excellent retention rates and postoperative visual acuity in patients with corneal graft failure, however, poor visual outcomes still occur in patients with underlying autoimmune disease. Methods We reviewed the current literature to determine the results of keratoprosthesis in patients with blinding autoimmune diseases. Results Much of the published literature on keratoprosthesis fails to clearly differentiate outcomes on the basis of the underlying disorder. Based on available evidence, inflammation, retinal detachment, and glaucoma appear to be the most significant complications after keratoprosthesis in autoimmune patients, and a diagnosis of mucous membrane pemphigoid or Stevens Johnson Syndrome appears to be associated with a significantly higher complication rate than other preoperative conditions. Conclusion Patients with autoimmune diseases carry the worst prognosis for success with keratoprosthesis. Improvement in clinical outcomes might be achieved with changes in keratoprosthesis design and material, perioperative therapy, and/or surgical technique. Possible approaches to complications after Boston keratoprosthesis in patients with underlying autoimmune diseases will be discussed. [source] The taming of the shrew?ACTA OPHTHALMOLOGICA, Issue 5 2009The immunology of corneal transplantation Abstract. Corneal transplantation, first reported a century ago, is the oldest and most frequent form of solid tissue transplantation. Although keratoplasty is also considered as the most successful transplant procedure, several studies indicate that the long term survival of corneal grafts is even lower than that of transplanted parenchymatous organs. Despite the immune privilege enjoyed by the cornea and anterior segment of the eye, immunologic graft rejection is a major limitation to corneal transplantation. This review gives an update on corneal immunobiology and the mechanisms of corneal graft rejection, focusing on antigen presentation, as well as on the molecular and cellular mediators of this particular immune response. [source] Corneal oedema after cataract surgery: predisposing factors and corneal graft outcomeACTA OPHTHALMOLOGICA, Issue 2 2009Margareta Claesson Abstract. Purpose:, Pseudophakic bullous keratopathy (PBK) is one of the main indications for corneal transplantation. Graft survival and visual outcome in this group are often poorer than for other indications. The aim of this study was to find risk factors for developing corneal oedema after cataract surgery and factors that influence the subsequent survival of the graft and the visual outcome. Methods:, We carried out an observational, retrospective cohort study using data from the Swedish Cornea Transplant Register and patient medical records. A total of 273 patients whose indication for corneal transplantation was corneal oedema after cataract surgery were included in the study. Multiple logistic regression analysis and, where appropriate, univariate analyses were applied. Results:, A total of 43% of the patients developed persistent corneal oedema immediately after cataract surgery, the main risk factors for which were phacoemulsification and pre-existing endothelial disease. Almost a third (32%) of the transplants for PBK failed within 2 years, for which rejection and other postoperative complications increased the risk. Half (50%) the patients had visual acuity , 0.1 at 2 years after keratoplasty. Comorbidity, increasing duration of the bullous keratopathy and increasing age affected the visual outcome negatively. Conclusions:, Phacoemulsification was a risk factor for immediate persistent corneal oedema after cataract surgery, although it did not increase the overall risk of developing PBK. However, transplants for immediate PBK had a better survival rate than those for later onset PBK. Shorter duration of PBK and intraocular lens exchange at the time of penetrating keratoplasty increased the likelihood of good visual acuity. [source] The taming of the shrew or corneal transplantation: past, present and futureACTA OPHTHALMOLOGICA, Issue 2008U PLEYER Keratoplasty has definitely its paradoxes. It has been the first successful transplantation in man and is with approx. 100. 000 grafts/year easily the most frequent allograft in human medicine. At the same time it is still the least understood form of transplantation in respect to its biology. It is both, the most successfull as well as probably the most underestimated procedure regarding its risks in clinical transplantation. Indeed, the common assumtion, that corneal transplantation is a safe procedure with good prognosis may have hindered more intensive effort of research in this field. This lecture aims to highlight significant milestones in the rich history of corneal transplantation, and to pay tribute to the many inspired and dedicated individuals involved in the development of keratoplasty. There are still limitations to corneal transplantation, and corneal allograft rejection still poses the greatest challenge to the modern corneal surgeon. Therefore, particular emphasis will be paid to recent efforts and developments to overcome this challenge. [source] A century of corneal transplantationCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2005Douglas J Coster FRANZCO No abstract is available for this article. [source] | ||||||||||