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: 6880001
• 负责人: Jeffrey L Bennett
• 金额: $ 15.4万
• 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/6880001
• 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（由申请方提供）：急性带状隐匿性外层视网膜病变、多发性渐逝性白色斑点综合征、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、点状内层脉络膜病变和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，并且受影响的个体在其临床过程中可能从一种状况演变为另一种状况。视力丧失可能从轻度到重度不等。然而，到目前为止，没有绝对的标准来定义疾病亚型，没有可用的标记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性脉络膜视网膜病变的相关谱仍然存在争议。 病理标本显示B细胞为主的炎症浸润与抗体沉积提供了一个理论基础，我们的假设，抗体在这些疾病的发病机制中发挥作用，并针对视网膜或脉络膜抗原，触发或传播疾病。 为筛选隐匿性脉络膜视网膜病变（OC）特异性抗原，我们将：（1）从人葡萄膜cDNA表达文库和随机肽文库中筛选能与OC患者血清发生反应的克隆;（2）从QC患者和对照眼葡萄膜炎患者血清中筛选候选QC特异性抗原和肽，以确定其疾病特异性;和（3）使用分子生物学技术表征OC特异性克隆并研究它们在视网膜和脉络膜中的表达模式。 OC特异性标志物的鉴定将有助于将这些隐匿性炎性疾病分类为特定的疾病分类实体，产生诊断临床前和临床疾病的生物标志物，并制定治疗策略以防止受影响个体的视力丧失。