Antigen Identification in Occult Chorioretinopathies

隐匿性脉络膜视网膜病变中的抗原鉴定

• 批准号: 6725212
• 负责人: Jeffrey L Bennett
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725212
• 关键词: affinity chromatography; antibody specificity; antigen antibody reaction; antiserum; biomarker; chorioretinitis; choroid uvea; choroiditis; clinical research; confocal scanning microscopy; enzyme linked immunosorbent assay; eye disorder diagnosis; genetic library; genetic screening; human subject; in situ hybridization; molecular cloning; nucleic acid sequence; open reading frames; pathologic process; peptide library; polymerase chain reaction; retina disorder; serology /serodiagnosis; uveitis; western blottings

DESCRIPTION (provided by applicant): Acute zonal occult outer retinopathy, multiple evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic blind spot enlargement syndrome, multifocal choroiditis, punctuate inner choroidopathy, and diffuse subretinal fibrosis syndrome are a group of chorioretinal inflammatory disorders of unknown etiology. These disorders possess common clinical features, and affected individuals may evolve from one condition to another during their clinical course. Vision loss may vary from mild to severe. To date, however, there are no absolute criteria to define disease subtypes, no available markers to diagnose disease or gauge prognosis, and no effective therapies. As a result, debate remains as to whether these disorders represent a related spectrum of inflammatory chorioretinopathies. Pathologic specimens have revealed a B-cell predominant inflammatory infiltrate with antibody deposition providing a rationale for our hypothesis that antibodies play a role in the pathogenesis of these disorders and are directed against retinal or choroidal antigens that trigger or propagate disease. To identify an antigen specific to occult chorioretinopathies (OC) we will: (1) identify clones in a human uveal cDNA expression Library and a random peptide library whose products react with serum from OC patients; (2) determine the disease-specificity of candidate QC-specific antigens and peptides by screening sera from patients with QC and control ocular uveitides; and (3) characterize, using molecular biologic techniques, OC-specific clones and study their pattern of expression in the retina and choroid. Identification of OC-specific markers will help classify these occult inflammatory disorders as a specific nosologic entity, generate biologic markers to diagnose preclinical and clinical disease, and develop therapeutic strategies to prevent loss of vision in affected individuals.

描述（申请人提供）：急性带状隐匿性外视网膜病变、多发性消失性白点综合征、急性黄斑神经视网膜病变、急性特发性盲点扩大综合征、多灶性脉络膜炎、点状内脉络膜病、弥漫性视网膜下纤维化综合征是一组病因不明的脉络膜视网膜炎性疾病。这些疾病具有共同的临床特征，受影响的个体可能在其临床过程中从一种情况演变到另一种情况。视力丧失可能从轻微到严重不等。然而，到目前为止，还没有确定疾病亚型的绝对标准，没有可用的标志物来诊断疾病或衡量预后，也没有有效的治疗方法。因此，关于这些疾病是否代表炎症性脉络膜视网膜病变的相关谱仍存在争议。病理标本显示以b细胞为主的炎症浸润伴抗体沉积，这为我们的假设提供了基本原理，即抗体在这些疾病的发病机制中起作用，并针对触发或传播疾病的视网膜或脉络膜抗原。为了鉴定隐匿性绒毛膜视网膜病变（occ）的特异性抗原，我们将：(1)在人类葡萄膜cDNA表达文库和随机肽文库中鉴定克隆，其产物与OC患者的血清发生反应；(2)通过筛选QC患者血清和对照眼黄素，确定候选QC特异性抗原和肽的疾病特异性；(3)利用分子生物学技术鉴定oc特异性克隆并研究其在视网膜和脉络膜中的表达模式。识别oc特异性标志物将有助于将这些隐匿性炎性疾病分类为特定的病理性实体，产生生物标志物来诊断临床前和临床疾病，并制定治疗策略以防止受影响个体的视力丧失。