Objective: This project will study epigenetic mechanisms, the inheritance of (both Mendelian and complex) and biomarkers of Immune Mediated Eye Diseases, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when mutated or demethylated or aceytylated, cause immune mediated eye disease, and the pathophysiology through which they act.

Study Population: The number of participants to be enrolled has no logical upper limit, but will be at 500 during the next 5 years. Race, age and sex matched controls, anonymous volunteers will also be needed to donate a blood sample. The study consists of ascertaining individuals and families with multiple individuals, if possible, affected by immune mediated ocular disease.

Design: These patients and their families will undergo detailed ophthalmologic examinations and, where indicated, additional non-investigational examinations to characterize their ocular status. A blood sample will be collected from each individual for isolation of DNA and serum, and in some individuals for biochemical studies and lymphoblastoid transformation to establish a renewable source of DNA. Demethylation probing (and acetylation when available), linkage analysis, physical mapping, and mutational screening will be carried out to identify the specific gene and/or mutations in it that are associated with ocular inflammatory disease in patients and their families. DNA samples from the AREDS study, held under the DCR/NEI Repository protocol (07-EI-0168), will also be used for analysis. If necessary, the gene product or blood sample will be characterized biochemically.

Outcome Measures: Demethylation results will be reported using statistical analysis performed using the t test or ANOVA and post-hoc testing with Fisher's least significant difference test. Unless otherwise noted, results are presented as the mean _ SEM. Linkage will be determined using the lod score method and mutations in specific genes will be assessed using a combination of residue conservation, blosum score, and molecular modeling. Association will be determined using chi-square and Fisher exact tests. Biochemical, metabolic, and physiological effects will be individualized to the specific assay.

• INCLUSION CRITERIA:

Participants with the following will be recruited:

• Individuals or family members of individuals with immune mediated retinal disorders, including uveitis, age related macular degeneration, and diabetic retinopathy.
• Adults must be capable of providing their own consent.
• All participants must be able to cooperate with study examination and phlebotomy.
• Children must be older than 4 years of age.

EXCLUSION CRITERIA:

• Individuals with diseases, infections, or trauma that mimic immune medicated retinal disorders.
• Children requiring sedation for study procedures.