This study will identify genes that are associated with inflammation or degeneration of the
retina (membrane lining the back of the eye that relays vision signals to the brain). It is
thought that many retinal conditions are due to an altered immune system and are based on how
the person s genes function and communicate.
People 4 years of age or older who have a retinal condition such as uveitis, age-related
macular degeneration or diabetic retinopathy may be eligible for this study. Healthy
volunteers and healthy people who have a family member with one of these conditions are also
eligible. Patients with inherited retinal degeneration are excluded.
Participants undergo the following tests and procedures:
- Eye examination to assess visual acuity (eye chart test) and eye pressure, and to
examine the pupils, lenses, retina and eye movements. Photographs of the inside of the
eye may also be taken. The pupils are dilated with drops for this examination.
- Blood draw for genetic testing.
Participants may also undergo one or more of the following tests:
- Optical coherence tomography. This is a type of photograph of the back of the eye to
measure thickness of the retina.
- Fluorescein angiography and indocyanine green angiography. Pictures of the eye s blood
vessels are taken using either a fluorescein or indocyanine green dye. The dye is
injected into a vein in an arm and travels to the blood vessels in the eyes. A camera
takes pictures of the dye as it flows through the blood vessels.
- Electroretinogram (ERG) to measure retinal function. The patient sits in a dark room for
30 minutes with his or her eyes patched. Then, a small metal disk electrode is taped to
the forehead, the eye patches are removed, the surface of the eye is numbed with eye
drops, and contact lenses are placed on the eyes. The patient then watches flashing
lights. The contact lenses sense small electrical signals generated by the retina when
the light flashes.
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 genetically mutated or
epigenetically regulated, 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 1,000 during the next five 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
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 and immunophenotyped using Flow
Cytometry. Serum will be isolated for testing serological markers. One or more
sub-populations of cells (including but not limited to CD4 plus and CD8 plus T cells, B
cells, CD14 plus monocytes, dendritic cells, NK cells, neutrophils and granulocytes) will be
isolated. DNA, RNA and chromatin may be isolated for further gene expression profiling and
epigenetic studies. Association of genetic or epigenetic changes with ocular inflammatory
disease in patients and their families will be identified using one of the techniques
including but not limited to DNA-seq, BS-seq, MeDIP-seq, ChIP-seq, RNA-seq, microarray, PCR,
and multicolor Flow Cytometry staining. 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.
Immunophenotyping, gene expression and epigenetic changes 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.
Biochemical, metabolic, and physiological effects will be individualized to the specific
- 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.
- Individuals with diseases, infections, or trauma that mimic immune medicated retinal
- Children requiring sedation for study procedures.