Pathogenesis of Onchocercal Keratitis (River Blindness)

Abstract

SUMMARY Onchocerciasis is a major cause of blindness. Although the World Health Organization has been successful in reducing onchocerciasis as a public health problem in parts of West Africa, there remain an estimated 17 million people infected with Onchocerca volvulus, the parasite that causes this disease. Ocular pathology can be manifested in any part of the eye, although disease manifestations are frequently characterized as either posterior or anterior eye disease. This review focuses on onchocerca-mediated keratitis that results from an inflammatory response in the anterior portion of the eye and summarizes what is currently known about human disease. This review also describes studies with experimental models that have been established to determine the immunological mechanisms underlying interstitial keratitis. The pathogenesis of keratitis is thought to be due to the host inflammatory response to degenerating parasites in the eye; therefore, the primary clinical symptoms of onchocercal keratitis (corneal opacification and neovascularization) are induced after injection of soluble O. volvulus antigens into the corneal stroma. Experimental approaches have demonstrated an essential role for sensitized T helper cells and shown that cytokines can regulate the severity of keratitis by controlling recruitment of inflammatory cells into the cornea. Chemokines are also important in inflammatory cell recruitment to the cornea, and their role in onchocerciasis is being examined. Further understanding of the molecular basis of the development of onchocercal keratitis may lead to novel approaches to immunologically based intervention.

Recent Updates on Onchocerciasis: Diagnosis and Treatment

“…During adulthood, the female worm sheds hundreds of thousands of microfilariae measuring 220-360 mm [6] that migrate through the skin of the human host, with particular affinity for the eyes. The inflammatory response against dying microfilariae over years of repeated infection causes the gradual and eventually blinding sclerosal opacification of the anterior eye by local inflammation and of the posterior eye by auto- immune mechanisms [7]. The O. volvulus life cycle continues on uptake of microfilariae by the blackfly during a blood meal.…”

Immunopathogenesis of <I>Onchocerca volvulus</I> keratitis (river blindness): a novel role for TLR4 and endosymbiotic <I>Wolbachia</I> bacteria

“…3,28 After injection of parasite antigens into the cornea, production of neutrophil and eosinophil chemokines is up-regulated in the cornea, and expression of vascular adhesion molecules PECAM-1 and ICAM-1 on limbal vessels is elevated. 29,30 Neutrophils and eosinophils are then recruited to the corneal stroma in a biphasic manner, with neutrophils infiltrating within 24 h, and eosinophils predominating after 72 h. 3,31 The physical presence of the cellular infiltrate, combined with degranulation and release of cytotoxic mediators, lead to disruption of normal corneal structure, loss of corneal clarity and visual impairment.…”

“…While alive, the larvae appear to cause no disease; however, when they die, especially after chemotherapy, the host response to degenerating worms can result in severe inflammatory responses that result in skin changes, hydrocele formation, progressive loss of vision. 3,4 Until recently, the general understanding was that filarial products per se are the major stimulus for the inflammatory responses associated with this disease. The discovery and characterization of endosymbiotic Wolbachia bacteria in the filarial nematode have led to major changes in the accepted paradigms.…”

Onchocerciasis in Anambra State, Southeast Nigeria: endemicity and clinical manifestations

“…However, the migratory microfilariae are able to induce intense inflammatory responses, especially upon their death. The clinical symptoms of the disease are a result of the host inflammatory response to the dead microfilariae 6. Dying microfilariae have also recently been discovered to release Wolbachia -derived antigens, triggering innate immune responses and producing inflammation and its associated morbidity 7–9.…”