July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Age-related macular degeneration (AMD) like pathology in murine cytomegalovirus (MCMV) latently infected eyes of BALB/c mice following systemic neonatal infection
Author Affiliations & Notes
  • Ming Zhang
    Augusta University, Augusta, Georgia, United States
  • Xinglou Liu
    Augusta University, Augusta, Georgia, United States
  • jinxian Xu
    Augusta University, Augusta, Georgia, United States
  • Brendan Marshall
    Augusta University, Augusta, Georgia, United States
  • Zheng Dong
    Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Ming Zhang, None; Xinglou Liu, None; jinxian Xu, None; Brendan Marshall, None; Zheng Dong, None
  • Footnotes
    Support  NH Grant EY026642
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 775. doi:https://doi.org/
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      Ming Zhang, Xinglou Liu, jinxian Xu, Brendan Marshall, Zheng Dong; Age-related macular degeneration (AMD) like pathology in murine cytomegalovirus (MCMV) latently infected eyes of BALB/c mice following systemic neonatal infection. Invest. Ophthalmol. Vis. Sci. 2019;60(9):775. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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. The purpose of this study was to determine if latent ocular MCMV infection is associated with production of inflammatory/angiogenetic factors and development of an AMD like pathology.

Methods : MCMV (50 pfu per mouse) or medium as control was peritoneally injected into BALB/c mice at <3 days after birth. Eyes were collected at 4, and 8 months post infection (p.i.) and analyzed for the presence of virus by PCR, for expression of MCMV immediate early (IE) gene transcripts (IE1, IE3) and gB late gene transcripts and inflammatory/angiogenic gene transcripts by real time RT-PCR, for proteins involved in inflammatory responses by ELISA or Western Blot. Eyes were also examined by electron microscopy (EM) and H&E staining.

Results : At 4 months p.i., no ocular replicating virus was detected, although virus DNA was still detected in eyes of infected mice (9/9). Expression of MCMV IE gene transcripts was detected in the majority of latently infected eyes (6/9 for IE1 and 7/9 for IE3). However, expression of gB late gene transcripts was detected in only 1 of 9 latently infected eyes. mRNA and protein levels of TGF-β, CCL5 and angiopoietin I were significantly higher in latently infected eyes compared to control eyes. Although degeneration of photoreceptors was not observed in the neural retina, AMD like pathology was observed by EM in 3 of 3 MCMV latently infected eyes at 4 months p.i. but not in age-matched uninfected control eyes, nor in acutely infected eyes at day 14 p.i. Pathological changes observed included a) focal thickening of Bruch's membrane with lipid deposits; b) platelet attachment and cell death in the choroidal capillaries; c) many large lipid vesicles inside RPE cells. In addition, basal laminar deposits (BlamD) were noted in all latently infected eyes at 8 months p.i.

Conclusions : MCMV disseminates to and remains latent in the choroid and RPE cells following systemic infection of neonatal BALB/c mice. Latent infection and reactivation of MCMV genes in the eye induces in situ inflammation and development of AMD like pathology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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