Antibiotic Treatment Exacerbates Focal Retinal Degeneration in a Mouse Model of AMD

Authors

• L Guedez
• N Popp
• M Abu-Asab
• H Qian
• Y Li
• CC Chan

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. Inflammation, oxidative stress, and cell death are involved in the pathogenesis of retinal degeneration in AMD. Board spectrum antibiotics have been reported to decrease inflammation in autoimmune uveitis. We investigated whether antibiotics might have a similar anti-inflammatory effect in AMD. To this end, age-matched Ccl2/Cx3cr1 double knock-out (DKO) mice, an AMD mouse model, were treated or untreated for three months with antibiotics (Vancomycin, Ampicillin, Neomycin and Metronidazole) delivered orally in their drinking water. Funduscopy was performed monthly; visual function was assessed by ERG. Three months post-treatment, the eyes were enucleated for histology, ultrastructure-EM and RNA extraction. Transcripts for Il-1β, Tnf-α and oxidative stress factors were detected by qRT-PCR. After 3 months, antibiotic treated mice showed significantly higher funduscopy clinical grading scores, indicative of increased focal retinal degeneration. Retina function test of treated mice demonstrated a decline in their dark-adapted ERG response. In contrast to controls, histology from treated mice revealed a prominent thinning and extensive focal atrophy of their photoreceptors; EM showed apoptotic-cell death. Unlike Il-1β mRNA levels, Tnf-α and iNos mRNA were significantly elevated in antibiotic treated eyes. This study has demonstrated that antibiotics exacerbate retinal degeneration in an AMD mouse model. The key pathological aspects and decline in visual function were severely worsened by antibiotics. The increase in inflammation and oxidative-stress markers underscores their role in AMD pathogenesis.

Scientific Focus Area: Neuroscience

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