14
Ⅲ Yamaki et al.
Ⅲ
Antigens in Melanocytes
Identifying the target antigens of the autoimmune reactions involved
in this disease is extremely important. Melanocytes contain many anti-
gens, which, for purposes of analysis, can be divided into four groups:
soluble proteins, insoluble proteins, sodium dodecyl sulfate–insoluble
proteins, and already known proteins specifically expressed in melano-
cytes (e.g., tyrosinase family proteins). To identify the candidate antigens
specific to VKH disease, a lymphocyte proliferation assay is performed
against each group of the proteins, and the pathogenic potential of each
in the experimental animals is studied.
Ⅲ
Animal Studies
Tyrosinase Family Proteins
The tyrosinase family proteins are the enzymes for melanin formation
and are expressed specifically in melanocytes. Tyrosinase catalyzes the
hydroxylation of tyrosine to form dopa and the oxidation of dopa to
dopaquinone.8 Tyrosinase-related protein 1 (TRP1), dihydroxyindole-2-
carboxylic acid oxidase, converts dihydroxyindole-2-carboxylic acid to Eu-
melanin.9 Tyrosinase-related protein 2 (TRP2), dopachrome tautomer-
ase, converts dopachrome to dihydroxyindole-2-carboxylic acid.10
Clinical Features of VKH Disease Induced in Rats
Immunization of rats with tyrosinase, TRP1, or TRP2 can induce au-
toimmune disease.11 Peak inflammation occurs on days 14 through 21
postimmunization, after which the inflammation gradually subsides. At
the height of the disease, a large amount of fibrin in the anterior cham-
ber, which leads to pupillary block, is observed in severely affected eyes. In
some cases, the color of the fundus reflex gradually changes from dark red
to whitish red. This fundus reflection resembles the so-called sunset-glow
fundus of VKH patients and develops in rats by 2 to 4 months after
immunization (Fig. 1C).7
Histological Findings in the Eye
The inflammatory cells infiltrate the anterior and posterior chambers,
the iris, and the ciliary body. The iris is extremely swollen with the accu-
mulation of epithelioid cells (Fig. 2A, B). Depigmentation, pigment dis-
persion, and pigment phagocytosis also are observed in some of the le-
sions (see Fig. 2B).7
In severely affected eyes, the retina is detached from the retinal pig-