Experimental ocular onchocerciasis in cynomolgus monkeys

Area of Science:

• Veterinary Ophthalmology
• Parasitology
• Immunology

Background:

• Ocular onchocerciasis, a leading cause of infectious blindness, is caused by Onchocerca volvulus.
• Animal models are crucial for understanding disease pathogenesis and testing interventions.

Purpose of the Study:

• To establish a cynomolgus monkey model of ocular onchocerciasis using Onchocerca lienalis microfilariae.
• To evaluate the impact of diethylcarbamazine citrate (DEC) on ocular inflammation in this model.

Main Methods:

• Cynomolgus monkeys were infected with O. lienalis microfilariae via various ocular routes (intracorneal, subconjunctival, intracameral, intravitreal).
• Some infected monkeys received daily oral DEC treatment.
• Ocular inflammation and microfilarial presence were assessed using slit-lamp biomicroscopy.
• In vitro leukocyte proliferation assays and in vivo antibody responses were measured.

Main Results:

• Living microfilariae were observed in the anterior chamber and vitreous following intravitreal injection, eliciting inflammatory responses with eosinophils and macrophages.
• Intracorneal microfilariae caused minimal corneal inflammation, while intracameral injection induced anterior uveitis.
• DEC treatment did not substantially alter the extent of ocular inflammation.
• Infected monkeys showed suppressed or absent in vitro leukocyte proliferation to microfilarial antigen and reduced mitogen responses.
• Circulating IgG antibodies were detected, but showed no clear correlation with ocular inflammation severity.

Conclusions:

• The Onchocerca lienalis microfilariae model effectively replicates key aspects of ocular onchocerciasis pathogenesis in cynomolgus monkeys.
• DEC treatment demonstrated limited efficacy in reducing ocular inflammation in this model.
• The study highlights complex immune responses, including suppressed cellular immunity and circulating antibodies, in ocular onchocerciasis.