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Liliana Guedez, Nicholas Popp, DeFen Shen, Haohua Qian, Yichao Li, Chi-Chao Chan; Antibiotic Treatment Exacerbates Focal Retinal Degeneration in a Mouse Model of AMD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):276.
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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 by modulating the gut’s microflora. In this study, we investigated whether antibiotics might have a similar anti-inflammatory effect in AMD.
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 and RNA extraction. Transcripts for Il-1β, Tnf-α and iNos were detected by qRT-PCR.
After 3 months, antibiotic treated mice showed significantly higher clinical grading scores, indicative of increased focal retinal degeneration. Treated mice demonstrated a decline in their dark-adapted ERG response. In contrast to controls, ocular histology from treated mice revealed a prominent thinning and extensive focal atrophy of their photoreceptors. 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 of focal photoreceptor and RPE degeneration were severely worsened by antibiotics, with an associated decline in visual function. This contrasts against the beneficial anti-inflammatory effects of antibiotics in uveitis. We found that antibiotics significantly increased ocular expression of Tnf-α and the oxidative stress marker iNos. These findings support a role for inflammatory and oxidative stress pathways in retinal degeneration, warranting potential therapeutic intervention with oxidative stress inhibitors.
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