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Background The conventional drugs for preventing and treating graft rejection have the risks of inducing adverse responses.Researches showed that resolvinE1 (RvE1) can regulate Th1 cell-mediated immunoreaction.However,whether RvE1 has an inhibit effect on high-risk corneal graft is unclear now.Objective This study was to investigate the effects of RvE1 on immune rejection in high-risk corneal grafting mouse models.Methods SPF BALB/c mice were used as recipients,C57BL/6 mice were as donors.Ninety BALB/c mice were divided into corneal allograft group,corneal allograft+RvE1 group and corneal autograft group according to random number table.High-risk corneal graft models were established by corneal suturing for 14 days and followed by penetrating keratoplasty in recipients.Allograft keratoplasty was performed on the right eyes in the mice of corneal allograft group and corneal allograft+RvE1 group,and self-corneal graft rotated 180°was transplanted on the right eyes in the mice of autograft group.Normal saline solution of 10 μl was subconjunctivally injected after surgery once per day for 7 days in the corneal allograft group and corneal autograft group,and 10 μl RyE1 (1 μg) was used in the same way in the corneal allograft+RvE1 group.The recipient eyes were examined for potential rejection signals with slit lamp microscope and calculated the mean survival time and rejection index (RI).The histopathology was examined 21 days after modeling by hemotoxylin and eosin staining.The expressions of CD4 and interferon-γ (IFN-γ)in the corneas were detected by immunohistochemistry.Th1 cell (CD3+CD8a-IFN-γ+) percentage in draining lymph nodes were measured by flow cytometry.The mRNA expression levels of interleukin-2 (IL-2),tumor mecrosis factor-α (TNF-α),IFN-γ and T-bet were detected by real-time fluorescence quantitative PCR.Results The mean survival time of grafts was (28.5± 1.7) days in the corneal allograft group,and that in the corneal allograft+RvE1 group was (14.0±1.6) days,showing a significant difference between them (t =4.14,P＜0.001),while the survival rate was 100％ at 50 days after modeling in the corneal autograft group.Corneal edema and inflammatory cell infiltration were slight in the corneal allograft+RvE1 group and corneal autograft group compared with corneal allograft group.CD4 was positively expressed in corneal tissue,and IFN-γ was expressed in corneal epithelium.The CD4+ and IFN-γ+ cell number was decreased in the corneal allograft+RvE1 group and corneal autograft group compared with corneal allograft group under the fluorescence microscope.The percentages of Th1 cells in lymph cells of corneal allograft +RvE1 group and corneal autograft group were (1.07 ±0.25) ％,(0.85 ±0.12) ％,respectively,which were significnatly lower than (1.56±0.20) ％ in the corneal allograft group (both at P＜0.05).The expressions of IL-2,TNF-α,IFN-γ and T-bet mRNA in the corneal tissue in the corneal allograft group were higher than those in the corneal allograft+RvE1 group and corneal autograft group (all at P＜0.05).Conclusions RyE1 inhibits graft rejection in high-risk allograft mouse models probably by down-regulating the Th1 cell percentage in lymph cells and the expression of inflammationrelated cytokines in corneal grafts.
RESUMO
Objetive: The purpose of this study is to map the serological profile of candidates to corneal donation at Irmandade Santa Casa de Misericórdia de Porto Alegre, identifying the percentage of disposal by serology and the marker involved. Methods: There have been analised – retrospectively – the results of serology of all corneal donors, made between the period of 1st january 2006 and 31st december 2012. Data analised were related to age, gender and the results of serology pertinent to viral markers (HBsAg, anti-HBc, anti-HCV and anti-HIV), these, determined by immunosorbent tests (ELISA). Results: In the period of the study, there were 2476 corneal donors at the institution, with a major incidence on the male gender, on an average of 58.7 years old. 23% of retention because of serological unfitness was also identified, that is, 570 samples were non-negative to any of the used tests. The marker anti- HBc was the most prevalent on the studied population, followed by the Hepatitis C virus (HCV) and by the Human Immunodeficiency Virus (HIV). Conclusion: From the data found through this study, it is essential to have the participation of an efficient service on the serological evaluation of the candidates to corneal donation, once the security of the receptor must be taken into consideration in a population of donors with 23% of unfitness prevalence, in which the most prevalent marker is the one of Hepatits B. .
Objetivo: O intento deste desígnio é mapear o perfil sorológico dos candidatos a doação de córneas na Irmandade Santa Casa de Misericórdia de Porto Alegre, identificando o percentual de descarte por sorologia e o marcador envolvido. Métodos: Foram analisados – retrospectivamente – os resultados da sorologia de todos os doadores de córneas compreendidos entre 01 de janeiro de 2006 a 31 de dezembro de 2012. Foram avaliados os dados de idade, sexo e os resultados da sorologia pertinentes aos marcadores virais (HBsAg, anti-HBc, anti-HCV e anti-HIV) determinados por testes imunoenzimáticos (ELISA). Resultados: No período coberto pelo estudo, houve 2476 doadores de córneas na instituição, com maior ocorrência do sexo masculino e média de 58,7 anos de idade. Foram verificados 23,0% de retenção por inaptidão sorológica, ou seja, 570 amostras mostraram-se não-negativas para qualquer dos testes empregados. O marcador anti-HBc foi o mais prevalente na população aferida, seguido pelo vírus da hepatite C (HCV) e pelo vírus da imunodeficiência humana (HIV). Conclusão: Diante dos dados encontrados por este estudo, torna-se decisiva a participação de um serviço eficaz no tangente à avaliação sorológica dos candidatos à doação de córnea, uma vez que a segurança do receptor deve ser considerada numa população de doadores com prevalência de retenção por inaptidão sorológica de 23,0%, donde o marcador mais prevalente é o de hepatite B. .
