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N. Grace Lee, Lindsay L. Wong, Dhanesh Amarnani, Suzanne K Freitag, Diane Bielenberg, Patricia A D'Amore, Leo A Kim; A Novel Murine Model of Orbital Inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3426.
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Orbital inflammation from Graves’ disease or nonspecific orbital inflammation can cause devastating compressive optic neuropathy. Current therapeutic options which primarily consist of steroids and decompression surgery may not be sufficient to resolve the optic neuropathy. Progress in this area is hindered by the lack of animal models of acute orbital inflammation. We have developed an animal protocol to induce inflammation in the murine orbit with the use of a skin sensitizer, oxazolone.
Eight-week-old female BALB/c mice were sensitized with a topical application of 2% oxazolone solution in olive oil/acetone (2:1 vol/vol) to the shaved abdomen. Five days after sensitization (day 0), the right eye was challenged with a 10uL orbital injection of 2% oxazolone solution. The left eye, serving as a control, received a sham injection of the vehicle alone (olive oil/acetone). Mice then underwent daily magnetic resonance imaging (MRI) before being euthanized at various time points. Their exenterated orbits were examined histologically.
Twenty-four hours following the orbital challenge, mice were observed to demonstrate mild proptosis and dermatitis. MRI on day 1 confirmed the findings of exophthalmos as well as retrobulbar inflammation and periorbital edema. On day 3, there was relative reduction of edema and proptosis compared to day 1. Histopathologic examination of the mouse orbit from day 1 to day 5 corroborated the MRI findings of periocular and intraocular inflammation consisting of neutrophils with a transition to chronic inflammation with lymphocytes by day 3 and early fibrosis on day 5.
We present a novel animal model of orbital inflammation utilizing a type 4 hypersensitivity reaction. This model should allow a better understanding of why the orbit is preferentially affected in certain systemic disorders and may provide a way to evaluate potential alternatives to steroid and surgical treatment.
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