Immunologic determinants of age-related macular degeneration

年龄相关性黄斑变性的免疫学决定因素

• 批准号: 9221330
• 负责人: Douglas A Jabs
• 金额: $ 40.44万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9221330
• 关键词: AIDS population; Acquired Immunodeficiency Syndrome; Age; Age related macular degeneration; Age-Years; Aging; Anti-Retroviral Agents; Archives; Biological; Biological Markers; Blindness; Blood specimen; C-reactive protein; CD8-Positive T-Lymphocytes; Cardiovascular Diseases; Cell Aging; Cohort Studies; Collaborations; Complement; Complex; Data; Defect; Deposition; Development; Diabetes Mellitus; Disease; Drusen; Elderly; Enrollment; Epidemiology; Eye diseases; Genetic Polymorphism; HIV; Immune; Immune response; Immune system; Immunologics; Incidence; Inflammation; Leukocytes; Longevity; Longitudinal Studies; Malignant Neoplasms; Medical; Metabolic Bone Diseases; Morbidity - disease rate; National Eye Institute; Neurocognitive Deficit; Opportunistic Infections; Organism; Participant; Pathogenesis; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Plasma; Population; Prevalence; Reading; Retinal; Risk; Risk Factors; Role; Serum; Specimen; Stroke; T-Cell Depletion; T-Lymphocyte; United States; Vaccines; Visit; Visual impairment; age related; aged; antiretroviral therapy; case control; chemokine; clinical application; cohort; design; follow-up; immune activation; immunosenescence; improved; monocyte; mortality; public health relevance; repository; senescence

 DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the major cause of visual impairment and blindness in persons > 65 years in the United States and the 3rd leading cause of blindness worldwide. Several lines of evidence have implicated immune activation and inflammation in the pathogenesis of AMD, including biomarkers of systemic inflammation as risk factors for AMD, complement deposition in drusen, complement factor and chemokine genetic polymorphisms as risk factors for AMD, and circulating activated monocytes in patients with AMD. Antiretroviral (ART) -treated, immunorestored, HIV-infected patients have accelerated/accentuated aging and a shortened life span due to age-related diseases, such as cardiovascular disease, stroke, and diabetes. Immunorestored, HIV-infected persons have immune system changes similar to those of >70 year-old HIV- uninfected persons, known as immunosenescence. Enrollment data from the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort show a ~4-fold greater prevalence (prevalence ~10%) of intermediate- stage AMD vs. that seen in an age-matched, HIV-uninfected cohort. LSOCA has enrolled 2092 participants with AIDS, has medical and treatment data, cryopreserved plasma and blood leukocyte specimens in a specimen repository from enrollment and every-6-month follow-up visits, and has an archive of 5- and 10-year follow-up retinal photographs, which will be graded at a Reading Center for incident AMD. Cryopreserved blood specimens will be evaluated for evidence of inflammation, immune (particularly monocyte) activation, and immunosenescence markers as risk factors for both prevalent and incident AMD, using a nested case-control design. Pathways and markers will be those known to be operative in both ART-treated, HIV infected persons, and in HIV-uninfected older persons. Biomarkers and pathways identified as relevant to AMD in the LSOCA cohort will be evaluated in cryopreserved specimens from the Age-Related Eye Disease Study (AREDS) cohort. These studies will lead to an improved understanding of the roles of inflammation, immune activation, and immunosenescence in the pathogenesis of AMD.

 描述(由申请人提供)：老年性黄斑变性(AMD)是美国65岁人群视力受损和失明的主要原因，也是全球第三大致盲原因。已有多条证据表明免疫激活和炎症与AMD的发病有关，包括全身炎症的生物标志物作为AMD的危险因素，补体在玻璃体中的沉积，补体因子和趋化因子基因多态性作为AMD的危险因素，以及AMD患者循环激活的单核细胞。经抗逆转录病毒(ART)治疗、免疫储存的艾滋病毒感染患者由于与年龄相关的疾病，如心血管疾病、中风和糖尿病，加速/加剧了衰老和寿命缩短。免疫储存，艾滋病毒感染者的免疫系统变化与70岁未感染艾滋病毒的人相似，称为免疫衰老。来自艾滋病眼部并发症纵向研究(LSOCA)队列的登记数据显示，与年龄匹配的未感染HIV的队列相比，中期AMD的患病率(患病率~10%)高出约4倍。LSOCA已经招募了2092名艾滋病患者，拥有医疗和治疗数据，从登记和每6个月的随访中将血浆和血液白细胞样本冷冻保存在样本库中，并有5年和10年随访视网膜照片的档案，这些照片将在AMD事件阅读中心评分。采用嵌套式病例对照设计，对冷冻保存的血液样本进行评估，以确定炎症、免疫(特别是单核细胞)激活和免疫衰老标记物作为AMD流行和发病的危险因素的证据。途径和标志物将是那些已知在接受抗逆转录病毒治疗的艾滋病毒感染者和未感染艾滋病毒的老年人中起作用的途径和标记物。在LSOCA队列中被确定为与AMD相关的生物标记物和途径将在年龄相关眼病研究(AREDS)队列的冷冻保存样本中进行评估。这些研究将有助于更好地理解炎症、免疫激活和免疫衰老在AMD发病机制中的作用。