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Liwen Feng, Kailai Nie, Wei Fan; Effects of smoking on retina in wild type and cfh+/- mice: A new model for non-exudative AMD?. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2267.
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Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and no effective therapy exists for non-exudative AMD at present. Complement factor H Y402H polymorphism promotes AMD-like pathology development, and previous research successfully built non-exudative AMD models used cfh+/- mice, however, it will take about 2 years. Smoking is the only controllable risk factor of AMD, and studies showed that smoking exposure results in oxidative stress and complement activation via the alternative complement pathway. Therefore, we hypothesize that a combination of smoking exposure and complement system dysregulation will promote mice exhibit an AMD phenotype.
Age-matched wild type (WT) and cfh+/-mice were exposed to smoking using a nose-only cigarette smoking exposure method for 3 months. The control mice fed ordinarily for 3 months. Mice were anesthetized for Optical Coherence Tonography examination, then sacrificed by cervical dislocation, eyes were enucleated immediately and fixed at 4% paraformaldehyde, dehydrated, and embedded in tissue-tek OCT compound. C3b/iC3b/C3c and Iba-1 were detected with the aid of immunofluorescence staining. RPE-choroid-sclera flat-mounts were prepared to detecte the tight junction of RPE by ZO-1 immunofluorescence staining. Images were captured with the Zeiss Imager Z2 fluorescence microscope.
Optical Coherence Tonography examination showed that hyperreflectivity of the outer retina, external to the ellipsoid zone (drusen-like deposition) in cfh+/- smoking mice. Compared to the control mice, both WT and cfh+/- smoking mice showed sub-RPE C3b/iC3b/C3c deposition, activation of microglia cells and impairment of the tight junction: zonula occludens-1 (ZO-1) in RPE. However, microglial activation was more significant in cfh+/- smoking mice: microglia cells presented at the photoreceptor-outer segment in cfh+/- smoking mice. In the WT and cfh+/- control mice, only synapses of microglia cells can be seen extending into the outer nuclear layer occasionally and this change was even more frequently in the WT smoking mice.
Our results support the hypothesis that cfh+/- smoking mice will exhibit early AMD characteristics in a shorter time. These changes demonstrate the combination of smoking exposure and complement system dysregulation as a viable mice model for AMD to study pathogenesis and treatment.
This is a 2020 ARVO Annual Meeting abstract.
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