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Mechanism of Retinal Damage in Autoimmune Retinopathy

自身免疫性视网膜病变的视网膜损伤机制

基本信息

批准号：
7455030
负责人：
GRAZYNA ADAMUS
金额：
$ 36.93万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7455030
关键词：
Affect Antibodies Antibody Specificity Antisense Oligonucleotides Apoptosis Apoptotic Autoantibodies Autoimmune Process Biological Markers Blindness Blood-Retinal Barrier Calcium Cell Death Cells Cessation of life Clinical Clinical Treatment Complex Development Electroretinography Evaluation Eye diseases Goals Grant In Vitro Malignant Neoplasms Mediating Medical Methods Modeling Numbers Pathogenicity Pathway interactions Patient Care Patients Phenotype Photoreceptors Phototransduction Property Proteins Range Rate Rattus Research Personnel Retina Retinal Retinal Degeneration Retinal Diseases Retinal Ganglion Cells Role Serum Specificity Symptoms Therapeutic Agents Therapeutic Intervention Time Tissues Visual impairment base caspase-3 cell type cytotoxicity enolase in vitro Model in vivo melanoma prevent programs recoverin protein response retinal damage

项目摘要

DESCRIPTION (provided by applicant): Retinal degeneration is one of the leading causes of visual loss in the world. Autoimmune retinopathies, including paraneoplastic retinopathies such as cancer-associated retinopathy and melanoma-associated retinopathy, are progressive visual impairments that are mediated by autoantibodies against retinal proteins. Autoimmune retinopathy is currently an untreatable eye disease, and an understanding of its pathogenicity is still incomplete. The proposed hypothesis is that autoantibodies induce retinopathy through the activation of apoptotic death in retinal cells by increasing intracellular calcium. A massive death of retinal cells leads to significant tissue damage, loss of vision, and finally, blindness. To determine general treatment strategies, assessment is needed of a common mechanism of retinopathy that is associated with autoantibodies of various retinal specificities. The long-term goal is to define the mechanism of retinal damage in autoimmune retinopathy and, based on these findings, to identify precise, critical time points for therapeutic intervention to treat clinical symptoms. The objectives of this proposal are to establish pathogenic properties of patients' anti-retinal antibodies using an in vivo rat model and in vitro methods, and to define clinical and electrophysiological markers (indicators) for seropositive patients in order to initiate optimum medical evaluation and care for these patients. To achieve these objectives, the following specific aims are proposed: (1) To determine whether autoantibodies of different anti-retinal specificities activate the same mechanism in initiating apoptosis in vitro, (2) To define the phenotype of retinopathy patients with specific anti-retinal autoantibodies, (3) To determine the role of autoantibodies in altering the function of retinal cells using the rat model and electroretinography, and (4) To examine possible pathways to stop apoptosis in treating retinal degeneration in the rat model of antibody-induced retinopathy.

描述（由申请人提供）：视网膜变性是世界上视力丧失的主要原因之一。自身免疫性视网膜病变，包括副肿瘤视网膜病变，如癌症相关视网膜病变和黑色素瘤相关视网膜病变，是由针对视网膜蛋白的自身抗体介导的进行性视力损害。自身免疫性视网膜病变目前是一种无法治愈的眼病，对其致病性的了解仍然不完整。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Electroretinographic findings in transplant chorioretinopathy.

移植脉络膜视网膜病变的视网膜电图检查结果。

DOI：
10.2147/opth.s12057
发表时间：
2010
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
0
作者：
Chan-Kai,BrianT;Yeh,Steven;Weleber,RichardG;Francis,PeterJ;Adamus,Grazyna;Witherspoon,SRobert;Lauer,AndreasK
通讯作者：
Lauer,AndreasK

Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy.

自身抗体靶标及其在副肿瘤性视网膜病的致病性中的癌症关系。

DOI：
10.1016/j.autrev.2009.01.002
发表时间：
2009-03
期刊：
AUTOIMMUNITY REVIEWS
影响因子：
13.6
作者：
Adamus, Grazyna
通讯作者：
Adamus, Grazyna

Molecular biomarkers for autoimmune retinopathies: significance of anti-transducin-alpha autoantibodies.

DOI：
10.1016/j.yexmp.2009.08.003
发表时间：
2009-12
期刊：
EXPERIMENTAL AND MOLECULAR PATHOLOGY
影响因子：
3.6
作者：
Adamus, Grazyna;Brown, Lori;Weleber, Richard G.
通讯作者：
Weleber, Richard G.

Antirecoverin antibodies and autoimmune retinopathy.

抗恢复蛋白抗体和自身免疫性视网膜病变。

DOI：
10.1001/archopht.118.11.1577
发表时间：
2000
期刊：
Archives of ophthalmology (Chicago, Ill. : 1960)
影响因子：
0
作者：
Adamus,G
通讯作者：
Adamus,G

Bilateral paraneoplastic optic neuropathy and unilateral retinal compromise in association with prostate cancer: a differential diagnostic challenge in a patient with unexplained visual loss.

与前列腺癌相关的双侧副肿瘤性视神经病变和单侧视网膜损害：对不明原因视力丧失患者的鉴别诊断挑战。

DOI：
10.1007/s10633-012-9327-0
发表时间：
2012
期刊：
Documenta ophthalmologica. Advances in ophthalmology
影响因子：
0
作者：
Carboni,Giovannella;Forma,Gina;Bond,AprilD;Adamus,Grazyna;Iannaccone,Alessandro
通讯作者：
Iannaccone,Alessandro