Melanin-Associated Antigen Induced Anterior Uveitis in Rats
Acute anterior uveitis is a recurrent immune-mediated inflammatory condition involving the iris and ciliary region in man and occurs in about 4/1000 individuals. Although it may be self-limiting, it may also be chronic and lead to irreversible eye damage including cataract and glaucoma. Photophobia, and pain, with hyperemia of the vessels, hypopheon, iridiocyclitis is typical and the condition is relatively responsive to steroids. However, in some instances, the disorder is unresponsive to treatment and may lead to blindness with glaucoma, cataract and retinopathy. HLA B27 appears to be involved. Humans are usually treated with steroids, however, there are also undesirable side effects, and the condition remains an area of unmet need. In veterinary medicine, horses suffer from an analogous anterior recurrent uveitis which often leads to blindness as well and was known in the past as “Moon Blindness”.
The most appropriate animal model for this condition is the MAA-induced uveitis model in rats. A special proprietary preparation of melanin-associated antigen (MAA) complexed with adjuvant is administered to Lewis Rats as an inoculation. An acute, recurrent immune-mediated iridiocyclitis develops and resolves over a 1-month period. Both the ophthalmological presentation and the histologic features are analogous to the human condition.
The success of this models centers on the MAA antigen. The antigen is an extract of bovine ocular melanin derived from the iris. The collection and processing of the antigen is a difficult and meticulous process which has been optimized and validated at CBI. Our characterized MAA induces uveitis by day 15 in all treated rats and the disease proceeds consistently between and among groups. Both topical steroids and systemic cyclosporine markedly and consistently suppress the inflammation. Topical cyclosporine also suppresses inflammation, but not to the degree of steroid and systemic cyclosporine.
A typical study design:
- Ten Lewis rats per group, vehicle, test article at 2-3 dose levels, positive control of topical dexamethasone or systemic cyclosporine
- Induce inflammation with MAA injection
- Slit lamp scoring of inflammation in anterior segment 3x weekly for four weeks
- Weekly body weights
- Necropsy with histopathologic examination of eye
- Complete report
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Normal ciliary process and sclera. HE 100x |
MAA-treated rat. There is marked inflammation of the ciliary process, iris, cornea and uvea. 200x |
MAA-treated rat. There is marked inflammation of the ciliary process, iris, cornea and uvea. 400x |