Atrophic Lesion Borders in AMD: What Can They Tell Us?

Vera Bonilha, PhD
The Cleveland Clinic Foundation (Cleveland, OH)
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2018
Disease:
Macular Degeneration
Award Amount:
$160,000
Grant Reference ID:
M2016079
Award Type:
Standard
Award Region:
US Midwestern

The Elizabeth Anderson Award for Macular Degeneration Research.

Vera Bonilha, PhD

Geographic Atrophy: Changes in the Retinal Pigment Epithelial and Inflammatory Cell Populations in the Region of Expanding Lesions

Summary

Age-related macular degeneration (AMD) is a complex disease leading to irreversible blindness, one that disproportionately affects the elderly population in industrialized countries. At the moment, a few effective treatments exist, but new treatments for different symptoms and stages of the disease are urgently needed. This research project will correlate imaging of the atrophic late-stage lesion of AMD donor eyes with findings from detailed morphological and cellular analyses in and around the leading edge of these lesions.

Details

Age-related macular degeneration (AMD) is a complex disease leading to irreversible blindness in elderly populations of primarily industrialized countries. Geographic atrophy (GA), the cause of both moderate and severe central visual loss in many AMD patients, is as yet untreatable in its late stages. Although the progression of this disease in patients has been well studied, only a few studies analyzed the cellular and molecular features of GA.

This research project will correlate diagnostic imaging performed in patients carrying the atrophic late-stage lesion of AMD, or GA, with detailed morphological and cellular analysis in and around the leading edge of these lesions.

Specific aim 1 of the project will correlate donor eye imaging findings with cellular and molecular proteins present in the retinal cells at the leading edge of the GA lesion. Specific aim 2 of the project will better define the role of the immune system in the pathology of the GA lesions.

Retinal imaging of patients is playing an increasingly important role in the diagnosis and treatment of AMD and retinal dystrophies. The proposed research is unique because it will validate clinical imaging findings with morphological and molecular findings of a large number of donor eyes at the edges of GA lesions and surrounding areas. The information gained from this study will aid in understanding the pathophysiological mechanisms causally involved in GA and may offer additional insight in clinical diagnosis and therapeutic decision-making for GA. In addition, the data will be analyzed in conjunction with other known AMD risk factors, such as age, genotype, oxidative stress and inflammatory components.

About the Researcher

As a graduate student with a split fellowship at Federal University of Rio de Janeiro (Brazil), and Cornell University in New York, I carried out research aimed at understanding the basic aspects of the retinal pigment epithelium (RPE), an all-important layer of tissue next to the retina that helps nourish and maintain its sensory cells. My research unraveled the mechanisms determining the unique distribution of proteins in the RPE apical surface. I analyzed the mechanisms regulating the expression and delivery of both endogenous and exogenous proteins to the RPE plasma membrane. As a project staff member at the Cleveland Clinic, I became interested in RPE aging. As the RPE ages, a number of structural and physiological changes occur. Although these changes are well known, the basic mechanisms determining them are frequently poorly understood. Initially, my research compared the structural changes in diseased and aged RPE cells. I analyzed the protein profile of both young and aged RPE from animal models. As an independent researcher in the Cleveland Clinic I am interested in studying the role of oxidative stress in RPE and retinal degeneration and in aging. Specifically, I am focusing on the regulation of oxidative stress-mediated RPE degeneration by the antioxidant protein DJ-1. Another research focus in the laboratory aims to untangle a detailed analysis of the changes in cell structure, inflammation and oxidative stress markers along the leading edge of postmortem eye tissues obtained from AMD donors with geographic atrophy lesions.

Personal Story

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly population in industrialized countries. It affects approximately 15 million people in the United States. Due to the aging baby boomer population, the National Eye Institute estimates that by 2050, the number of people with AMD may rise to 5.44 million.

AMD’s high prevalence in the aging population, the lack of understanding of the detailed molecular mechanisms underlying the initiation pathophysiological changes, and the lack of an effective treatment to prevent the early disease changes or to retard the late atrophic stages of this disease, highlight the urgent need for additional research on AMD. These factors led me into this field of research. AMD is a complex disease with both a genetic component and environmental risk factors, and my research projects aim to increase our understanding of the molecular basis of AMD.

BrightFocus Foundation’s support to AMD research, through its Macular Degeneration Research program, is extremely valuable because it funnels resources into pioneer research projects investigating both causes and potential prevention strategies and treatments. The vision research community is very appreciative of the donors that keep the BrightFocus Foundation mission so successful.

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