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PM pollution is related to neurotoxic and vascular effects in eye diseases such as glaucoma. This study investigates the adverse effects of PM exposure on visual function and retinal neurons. A versatile aerosol concentration enrichment system was used to expose mice to either control air or PM polluted air. Six months after PM exposure, visual function was measured by electroretinography (ERG). Hematoxylin and eosin staining and immunofluorescence staining were used for histopathological analysis. Protein markers of apoptosis, astrocytic reactivity, inflammatory cytokines, lipid peroxidation, protein nitration and DNA damage response were quantified with ELISA, western blot or detected using immunofluorescence and immunohistochemistry. After six months of exposure, PM-exposed mice responded poorly to light stimuli compared with those exposed to the control air. PM exposure caused retinal thinning and reduction in the expression of retinal ganglion cell-selective marker RNA-binding protein with multiple splicing (RBPMS). Further, positive TUNEL staining was observed in the inner nucleus and outer nuclear layers of the retinae after exposure to PM, which was accompanied by the activation of apoptosis signaling molecules p53, caspase-3 and Bax. PM induced the release of inflammatory cytokines including tumor necrosis factor-α and cleaved interleukin-1β. Furthermore, increased levels of 8-OHdG and γ-H2AX in the mouse retinea were indicative of DNA single and double strand breaks by PM exposure, which activated PARP-1 mediated DNA damage and repair. In conclusion, this study demonstrates sub-chronic systemic exposure to concentrated PM causes visual dysfunction and retinal neuronal degeneration. DATA AVAILABILITY: The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.
Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
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