Differences in Genes and Proteins in Active and Controlled Uveitis

Ocular inflammatory diseases, including uveitis, cause significant visual loss. Previous
non-human investigations have identified several cell types, receptor systems and metabolic
intermediates that have led to treatment approaches for human patients. However, information
on the human genetic expression of these steps in defined inflammatory disease states is
lacking. This non-intervention study proposes to obtain peripheral blood and tissue
specimens from patients enrolled in other intramural trials for ocular inflammatory diseases
and to apply contemporary cDNA microarray technologies for the analysis of differential gene
expression. Test results will not be reported to participants or used for diagnostic or
therapeutic purposes.

The study's primary objective is to identify unique gene expression profiles as well as
disease relevant genes for patients with ocular inflammatory disease at defined clinical
stages using cDNA microarray analysis. This will help provide further insight to understand
the pathological mechanisms and potential targets for treatment. Some 3,000-5,000 genes will
be examined starting with a selected set associated with interleukin (IL) proteins and their
receptors, and with tumor necrosis factors (TNF). Purified peripheral blood mononuclear
cells (or whole blood lysates using RNA isolation procedures) will be used to isolate total
RNA from these samples. Samples will be taken during periods of active or recurring
inflammatory disease and again during periods of quiescence after treatment. The microarray
tools and methods for genetic analysis are now available both at NEI and the collaborating
NIA laboratories.

A secondary objective is to analyze the circulating protein profiles in serum or other
available tissue or fluid specimens from patients with ocular inflammatory disease at the
same time points as described above. These samples will be analyzed using 2-dimensional
SDS-PAGE for profiling proteomic differences in patients at defined clinical stages. In-gel
digestion and subsequent sequence analysis by mass spectroscopy will be performed if
differentially expressed protein(s) of interest are to be identified. Other methods such as
flow cytometry analysis and proliferation assays using purified PBMCs will be used to
examine expression status of cell surface markers of interest (e.g., CD25) as well as
responses to antigen and mitogens at the peak and trough serum concentrations of daclizumab
therapy.

- INCLUSION CRITERIA:

1. Participant is 6 or more years of age.

2. Participant has a diagnosis of an ocular inflammatory disease of at least eight
weeks' duration prior to enrollment, requiring medical treatment to control the
ocular inflammation. This treatment must require using a corticosteroid (e.g.,
prednisone or equivalent) or an investigational treatment, or any combination of
two or more anti-inflammatory treatments, including for example prednisone,
cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil,
methotrexate, etc. Participants are anticipated to have, but are not restricted
to, the following conditions: scleritis, intermediate or posterior uveitis,
intermediate uveitis of the pars planitis subtype, sarcoidosis, the
Vogt-Koyanagi-Harada (VKH) syndrome, Behcet's disease, juvenile rheumatoid
arthritis (JRA), retinal vasculitis or sympathetic ophthalmia.

3. Participant is currently enrolled in another NEI protocol for one of the above
(or related) conditions that requires periodic visits to NIH for treatment
and/or evaluation.

4. Participant is able to understand and sign an informed consent (or applicable
assent) and if the participant is younger than the age 18 at enrollment, has a
parent or legal guardian who is able to understand and sign a consent form on
their behalf.

EXCLUSION CRITERIA:

1. Participant is under the age of 6 years.

2. Participant has inadequate vascular access to obtain a routine venous peripheral
whole blood specimen totaling up to 50 mL at a single visit.

3. Participants has an inadequate peripheral leukocyte count such that it would be
unlikely to provide an adequate RNA sample. For this purpose, a total leukocyte count
below 3 x 10(9)/L will exclude a participant at enrollment. Unless there is a
recognized medical condition likely to reduce leukocyte counts, blood counts from a
prior visit up to 5 weeks earlier may be used to determine eligibility for a first or
subsequent sample collection. (A participant who initially enrolls with an adequate
leukocyte count may remain enrolled if counts subsequently fall below the limit, but
will not have blood samples drawn for this protocol until the leukocyte count
recovers above the limit).