Abstract
BackgroundAngiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model.MethodsTo assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensisand the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM).ResultsInfection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective.ConclusionsThe current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.
Highlights
Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment
The animals were divided into six groups: normal control group, infected group, and four treatment groups
After 14 dpi, the treatment groups were fed with albendazole (20 mg/kg/d), albendazole combined with dexamethasone (0.5 mg/kg/d), albendazole combined with CPT (50 mg/kg/d) and albendazole combined with tanshinone II-A (TSII-A) (50 mg/kg/d), respectively
Summary
Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Punyagupta et al [6] analysed the clinical features of 484 cases of typical eosinophilic meningitis and found that 16 % of patients had visual impairment, while 12 % had an optic disc abnormality such as papilledema and atrophy, which implied that the actual incidence of ocular angiostrongyliasis is likely much higher than commonly appreciated (1 %) [6] Oral steroids such as dexamethasone combined with an anti-helminthic agent like albendazole have been the most effective and common therapy clinically so far for the damage to vision caused by this parasite [7], for the significant improvement of intraocular inflammation and visual acuity. This treatment does not always achieve complete recovery of vision, which severely interferes with the quality of life of patients [8] and leaves an unsolved problem for researchers nowadays
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