Biomarkers of Systemic Inflammation in Intermediate Age-Related Macular Degeneration

中度年龄相关性黄斑变性全身炎症的生物标志物

• 批准号: 10388398
• 负责人: ANNE M. LYNCH
• 金额: $ 39.13万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10388398
• 关键词: Address; Advanced Development; Affect; Age related macular degeneration; Anti-Inflammatory Agents; Biological Markers; Blindness; Blood; Blood specimen; C-reactive protein; Chronic; Chronic Disease; Clinical; Colorado; Complement; Complement Activation; DNA; Data; Development; Disease; Drusen; Early identification; Elderly; Epidemiology; Event; Exudative age-related macular degeneration; Future; Genes; Genetic; Genetic Risk; Goals; Individual; Inflammaging; Inflammation; Inflammatory; Interruption; Intervention; Knowledge; Link; Longitudinal cohort; Measures; Multimodal Imaging; Natural History; Obesity; Optical Coherence Tomography; Other Genetics; Outcome; Pathogenesis; Pathologic; Patients; Photoreceptors; Pilot Projects; Play; Prevention strategy; Process; Registries; Research; Retina; Risk; Risk Factors; Role; Secondary Prevention; Support System; Therapeutic Intervention; Thick; Thinness; Time; Vision; chemokine; circulating biomarkers; clinical risk; cohort; comorbidity; complement system; cytokine; epidemiologic data; genetic risk factor; genetic variant; geographic atrophy; healthy lifestyle; high risk; high risk population; imaging biomarker; inflammatory marker; insight; macula; novel; older patient; personalized approach; prevent; preventive intervention; recruit; systemic inflammatory response; targeted treatment

PROJECT SUMMARY/ABSTRACT Age-related macular degeneration (AMD), a chronic multifactorial disease primarily affecting the macula region of the retina, is a leading cause of vision loss in the elderly. AMD is a disease of the photoreceptor support system linked with local inflammatory events and complement activation-promotion genes. Apart from a small number of studies in advanced AMD, the significance of systemically assessed inflammation in AMD has not been adequately addressed. This is especially true for patients with intermediate AMD (iAMD), an early form of AMD, where we suggest that the presence of systemic inflammation may be a risk factor for iAMD progression to the visually threatening forms of advanced AMD. To address this knowledge gap, we conducted pilot studies to evaluate profiles of circulating inflammatory markers including complement, cytokines, chemokines, and high-sensitivity C-reactive protein (hsCRP) in patients with iAMD recruited into our Colorado AMD registry. We found compelling evidence that certain inflammatory biomarkers distinguished patients with and without iAMD, and most importantly patients with iAMD who progressed to advanced AMD. Furthermore, we found in iAMD patients a significant link between systemic levels of hsCRP, and choroidal thinning on optical coherence tomography (OCT), a finding which is one of the pathological events linked with AMD. In aggregate, these findings suggest that studying iAMD as we propose, can provide insights into early pathologic events in AMD and also allow one to identify those at highest risk for severe AMD and progressive visual loss. The purpose of the proposed study is to corroborate and expand on the findings from our novel pilot data in an adequately powered iAMD cohort and explore our hypothesis that among patients with iAMD an inflammatory biomarker profile will identify patients who will convert to advanced AMD. We will leverage our cohort's existing longitudinal blood samples linked to demographic and epidemiology data as well as DNA, multimodal image, and outcome data. We will address this hypothesis with two specific aims. In Aim 1 we will follow an iAMD cohort over time and, a) Identify the profile of inflammatory biomarkers that best distinguishes patients with iAMD who progress to advanced AMD, and b) Develop a dynamic risk score for AMD progression that combines AMD epidemiological, newly defined inflammatory profiles, and genetic risk factors. In Aim 2, we will focus on OCT imaging biomarkers previously established as risk factors for AMD progression. We will determine the relationships between circulating inflammatory biomarkers and both qualitative (e.g., reticular pseudodrusen) and quantitative (e.g., drusen volume and choroidal thickness) measures. We expect our study will show an important role for systemic inflammation in iAMD. This study will present an opportunity to better understand iAMD pathogenesis as well as for early identification of a high-risk group of individuals in which targeted interventions can be developed to interrupt the natural history of AMD by preventing iAMD progression to advanced AMD and vision loss.

项目总结/文摘