[Ocular onchocerciasis: a key role for Wolbachia]

Area of Science:

• Ophthalmology
• Parasitology
• Microbiology

Background:

• Onchocerciasis, or river blindness, is caused by the parasitic worm Onchocerca volvulus.
• Microfilariae migrating into the eye cause inflammation and blindness upon death, particularly after chemotherapy.
• The role of endosymbiotic bacteria in disease pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of Wolbachia endobacteria in the pathogenesis of ocular onchocerciasis.
• To evaluate the impact of Wolbachia depletion on inflammation and parasite development.
• To assess the potential of antibiotic treatment in managing river blindness.

Main Methods:

• A mouse model of corneal inflammation was utilized, involving direct injection of worm extracts into the corneal stroma.
• Worm extracts were treated with doxycycline to deplete Wolbachia, and compared with untreated worms and Wolbachia-free worms.
• Corneal stromal thickness, haze, and neutrophil infiltration were measured as indicators of inflammation.
• Worm burdens and embryogenesis were assessed in worms from patients treated with doxycycline.

Main Results:

• Doxycycline-treated worms (depleted of Wolbachia) induced significantly lower corneal stromal thickness, haze, and neutrophil infiltration compared to controls.
• Untreated worms and Wolbachia-free worms caused greater inflammatory responses.
• Worms from doxycycline-treated patients showed reduced Wolbachia loads and abnormal embryogenesis.
• These findings suggest Wolbachia are critical for parasite survival and fecundity.

Conclusions:

• Endosymbiotic Wolbachia bacteria are key contributors to the inflammatory processes underlying ocular onchocerciasis and river blindness.
• Depletion of Wolbachia via doxycycline treatment reduces ocular inflammation and impacts parasite development.
• Antibiotic therapy targeting Wolbachia presents a potential strategy to mitigate the severity of river blindness and its associated vision loss.