RESUMEN
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-2(k)) corneal epithelium over a C57BL/6 (H-2(b)) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2(d)) 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]-gamma(+)) 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.
Asunto(s)
Trasplante de Córnea/inmunología , Supervivencia de Injerto/inmunología , Donantes de Tejidos , Quimera por Trasplante/inmunología , Animales , Proliferación Celular , Células Cultivadas , Endotelio/inmunología , Interferón gamma/metabolismo , Masculino , Ratones , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Trasplante Homólogo/inmunologíaRESUMEN
PURPOSE: To refine the phenotype of idiopathic macular hypoplasia, also referred to as ateliotic macula, by describing a series of cases with this diagnosis. METHODS: A review of the clinical characteristics of four patients as documented in medical records with regard to refractive error, visual acuity, anterior segment examination, retinal findings, and ancillary tests such as electroretinography (ERG). RESULTS: All patients had oval circumscribed or diffuse areas in the posterior pole where the retina appeared not to have developed normally; the fovea was involved in three patients with reduced visual acuity, and one patient had parafoveal lesions with preserved visual acuity. There were three males and one females. Patients' age ranged from 4 to 16 years. Errors of refraction ranged from severe myopia to hypermetropia and mild astigmatism. The anterior segment was normal in all patients. Three patients had strabismus and two had nystagmus. ERG was normal in the one patient in whom it was performed. One patient was mosaic for trisomy of chromosome 9. CONCLUSIONS: The term idiopathic macular hypoplasia can be applied to a spectrum of abnormalities in which a localized area of the posterior pole has a primordial or underdeveloped appearance. Lesions involving the fovea result in poor acuity. Generalized retinal dysfunction is absent. At least one of the genes involved in macular development may be located on chromosome 9.