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Jinxian Xu, Xinyan Zhang, Brendan Marshall, Sylvia B Smith, Diego Gabriel Espinosa-Heidmann, Ming Zhang; Advanced age-related macular degeneration like pathology in aged BALB/c mice following systemic neonatal murine cytomegalovirus (MCMV) infection. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1118.
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AMD is the leading cause of blindness worldwide. Human cytomegalovirus has been shown to be a novel risk factor for the progression of AMD. Our previous studies have shown that MCMV disseminates to and remains latent in the choroid and RPE cells following systemic infection of neonatal BALB/c mice, which resulted in AMD like pathology including basal lamina deposits , basal linear deposits /drusen and subretinal drusenoid deposits at 8 months post inoculation (p.i.). The purpose of this study was to determine if advanced AMD like pathology, including geographic atrophy and/or choroidal neovascularization (CNV) develop in MCMV latently-infected BALB/c mice at a more advanced age.
MCMV (50 pfu per mouse) or medium as control was peritoneally injected into BALB/c mice at <3 days after birth. At 18 months p.i, optical coherence tomography (OCT) examinations were performed to monitor the integrity of retinal structure. The mice were sacrificed and eyes were collected and examined by electron microscopy (EM), as well as by H&E and immunohistochemical staining.
The mean retinal thickness in 26 eyes of MCMV latently infected aged mice was significantly lower than in eyes of 10 age matched controls at 18 months p.i. Severe photoreceptor degeneration (including disappearance of the entire outer nuclear layer in some areas) was observed in 7 of 26 eyes. Further pathological changes observed in these 7 eyes included CNV lesions (average 2 per eye) and retinal detachment, which were noted in 4 and 6 eyes respectively. The presence of CNV lesions was confirmed by staining with anti-CD31 antibody and isolectin B4. AMD like pathology was also observed by EM in all 4 eyes examined. Pathological changes included BlamD and SDD deposits, disruption of RPE structure together with loss of RPE and photoreceptor cells, as well as extensive choroidal platelet infiltration both within choroidal capillaries and in perivascular tissue. Furthermore, increased numbers of larger, thick-walled arterioles were also observed in the choroid of MCMV-infected mice.
Advanced AMD-like pathology, including geographic atrophy and CNV lesions, develops in aged BALB/c mice as a result of systemic neonatal MCMV infection. Latent ocular MCMV infection and reactivation of viral gene expression are critical to the development of AMD-like symptoms.
This is a 2020 ARVO Annual Meeting abstract.
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