Objective: This ancillary study will establish a repository of biospecimens to generate induced pluripotent stem (iPS) cells that can be differentiated into ocular cell types, to be used for study of molecular mechanisms of and development of treatments for age-related macular degeneration (AMD). This repository will allow the cells to be used to perform high throughput drug screens to identify novel potential therapeutic compounds. Although research involving multiple different ocular cell types from these patients may be performed, the vast majority of the work will be centered on the retinal pigment epithelium (RPE) and neural retina. RPE and/or neural retinal cells generated from the iPS cells of participants with AMD will be used to analyze molecular mechanisms involved in disease initiation and progression.
Study Population: We plan to recruit 100 participants across multiple sites with AMD from the original cohort of study participants enrolled in the AREDS2 who are returning for a 10 year in-clinic study visit and have donated DNA in the AREDS2 study. Up to two participants will be enrolled at NEI. Participants with the highest genetic burden as well as those with rare variants will be included in the population.
Design: A 520 blood sample will be collected from 350 participants with specific genetic variants that are identified prior to the start of the study. Up to 60 participants will be enrolled at NEI. All of these participants were previously enrolled in the AREDS2 protocol (07-EI-0025) and they are returning for a 10-year in-clinic study visit for further phenotyping and for assessing the long-term effects of the ARESD2 supplements. Collected samples will be used to analyze molecular mechanisms involved in disease initiation and progression. In addition, the iPS cell-derived ocular cells may be used to perform high throughput (HTP) drug screens aimed at suppressing the molecular phenotypes of the disease and to identify potential therapeutic agents for these diseases. This study will typically require only one visit by each participant.
Outcome Measures: The primary outcome is to develop a repository for iPS cells for investigators involved in vision research. Secondary outcomes include the assessment of potential therapies for the treatment of age related macular disorder (AMD). There are no specific participant-based clinical outcomes for this protocol. Participants will, in general, be seen only once for this protocol, as this is an ancillary study to the main study.
