Experimentally induced Vogt–Koyanagi–Harada disease in two Akita dogs

Abstract

We have investigated whether a Vogt–Koyanagi–Harada (VKH)-like disease can be induced in Akita dogs by immunizing them with tyrosinase related protein 1 (TRP1), and compared the alterations induced to those of Akita dogs with a spontaneously occurring disease that resembles human VKH disease. Two Akita dogs were immunized with a peptide mixture of human TRP1. The changes in the eyes were followed by slit-lamp biomicroscopy, ophthalmoscopy, and fluorescein angiography (FA). The eyes, skin, and brains were studied by standard histological methods at about 20 months after the first immunization in one dog (dog 1), and at 3 weeks after the second immunization in the second dog (dog 2). Both dogs developed chorioretinal disease 3–4 weeks after the first immunization. Many inflammatory cells infiltrated into the anterior chamber and anterior vitreous. The fundus showed geographic, multifocal exudative retinal detachments. Multifocal leakages of fluorescein were detected from the choroid. Histologically, exudative retinal detachment was present, and inflammatory cells were seen in the subretinal space in the eyes of dog 2 taken three weeks after the second immunization. The choroid was thickened by the infiltration of inflammatory cells in some lesions. Dalen–Fuchs nodules were seen in the eye of dog 2. Depigmentation, pigment dispersion, and infiltration of many inflammatory cells around hair follicles and vessels were seen in the skin taken three weeks post-immunization. The clinical course and changes in the eyes and skin were very similar to those seen in the Akita dogs with spontaneously occurring VKH disease. We concluded that a VKH-like disease had been induced in these dogs, and this supports the tentative conclusion that the spontaneously occurring chorioretinal disease in Akita dogs is VKH disease.

Introduction

In an earlier study, we showed that the spontaneous chorioretinal disease, called uveodermatological syndrome or Vogt–Koyanagi–Harada-like syndrome, in Akita dogs had the clinical and histological characteristics of human Vogt–Koyanagi–Harada disease (VKH) (Halliwell, 1982, Kern et al., 1985, Bedford, 1986, Lindley et al., 1990, Muller et al., 1992, Reusch et al., 1994, Goodhead, 1996). We tentatively concluded that this disease in the Akita dogs was equivalent to human VKH disease although there were some differences.

Clinically, the Akita dogs had bilateral panuveitis with exudative retinal detachments and multifocal leakages of fluorescein from the choroid at the early stage of the disease. In the late stage, depigmentation and pigmented spots were seen as in human VKH disease. Hair loss and multifocal depigmentation of the skins also developed in the late stage.

Histological examination of the eyes showed that inflammatory and epithelioid-like cells had infiltrated and accumulated in the iris, ciliary body, and choroid resulting in a very thickened iris and choroid. The retina in some areas was partially preserved, but in other areas, inflammatory changes in the choroid spread to the retina. In these areas, there was shortening of the rod outer segment (ROS) and/or partial destruction of the inner segments. In the most severely affected areas, both the choroid and retina were totally destroyed. In older dogs, depigmentation and pigment dispersion were seen in the choroid with the accumulation of epithelioid-like cells under and/or on the RPE.

All of these clinical and histological changes are very similar to that seen in humans with VKH disease (Perry and Font, 1977, Moorty et al., 1995, Chan et al., 1988). From these observations, we tentatively concluded that the spontaneously occurring chorioretinal disease in Akita dogs most likely corresponded to human VKH disease.

VKH disease in humans is an autoimmune disease against melanocytes and is mainly mediated by cellular immune responses (Kobayashi et al., 1998, Norose et al., 1990, Yamaki et al., 2000a, Gocho et al., 2001). Immunization of tyrosinase family proteins, e.g. tyrosinase or tyrosinase-related protein 1 (TRP1), induced a disease in rats that had characteristics of human VKH disease. If the spontaneously occurring chorioretinal disease in Akita dogs is equivalent to human VKH disease, we hypothesized that immunization of Akita dogs with TRP1 will induce a chorioretinal disease that would be identical to the spontaneously occurring disease (Yamaki et al., 2000a, Yamaki et al., 2000b). And if successful, we can then conclude that the spontaneously occurring chorioretinal disease in the Akita dog is indeed equivalent to human VKH disease, and these dogs can be used to study different aspects of VKH disease.