Uveitis

Summary: A validated rabbit TNFα  and MT Uveitis model with a clinically relevant reference compound and a comprehensive list of read-outs.

Model Description

Uveitis is one of the major ophthalmic diseases that results in blindness. It is an inflammatory disease that affects the uveal tract and it can involve vitreous, retina and optic nerve. Approximately 10% of the blindness in the United States is caused by uveitis and although current treatments, topically- or systemically-delivered steroids, are effective, these treatments come with significant side effects. More effective, faster acting, and longer lasting anti-inflammatory drugs with fewer side effects are desired to treat this disease.

Two well-known ways to induce this disease in rabbits are the tumor necrosis factor α (TNFα) and Mycobacterium tuberculosis (MT). TNFα is considered a primary cytokine that initiates the inflammatory cytokine cascade. When injected intravitreally, TNFα induces infiltration of inflammatory cells in the anterior uvea and the aqueous humor. MT, a pathogenic bacterium, is used to induce uveitis by ocular administration in animals sensitized with the Mycobacterium tuberculosis H37Ra antigen. 

At Experimentica, we have fully implemented and validated rabbit TNFα and MT Uveitis model with a clinically relevant reference compound and the most comprehensive list of read-outs. 

Outcomes and Read-Outs 

In vivo ophthalmic exams scores

Fig. 1. Ophthalmic scores of TNFα-induced uveitis rabbit eyes for anterior chamber cells (A), vitreal haze (B) and conjunctival hyperemia (C) using the modified Hackett-McDonald scale for ophthalmic exams. 
Fig. 1. Ophthalmic scores of TNFα-induced uveitis rabbit eyes for anterior chamber cells (A), vitreal haze (B) and conjunctival hyperemia (C) using the modified Hackett-McDonald scale for ophthalmic exams. Inflammation resolves spontaneously by day 14 after induction; resolution is accelerated in eyes treated with 0.05% Difluprednate. Red = untreated; blue = difluprednate. 
Fig. 2. Topical treatment with  three dosages of PPL-003, 0.05% difluprednate and vehicle on Mycobacterium Tuberculosis (MT) induced uveitis rabbit eyes for anterior chamber and vitreal haze using the modified Hackett-McDonald scale.
Fig. 2. Topical treatment with  three dosages of PPL-003, 0.05% difluprednate and vehicle on Mycobacterium tuberculosis (MT) induced uveitis rabbit eyes for anterior chamber and vitreal haze using the modified Hackett-McDonald scale. 

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