July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Latent Ocular Murine Cytomegalovirus (MCMV) exacerbates the development of Choroidal Neovascularization (CNV) in VEGF-Ahyper mice
Author Affiliations & Notes
  • jinxian Xu
    Cellular Biology and Anatomy, Augusta university, Augusta, Georgia, United States
  • Xinglou Liu
    Cellular Biology and Anatomy, Augusta university, Augusta, Georgia, United States
  • Brendan Marshall
    Cellular Biology and Anatomy, Augusta university, Augusta, Georgia, United States
  • Zheng Dong
    Cellular Biology and Anatomy, Augusta university, Augusta, Georgia, United States
  • Ming Zhang
    Cellular Biology and Anatomy, Augusta university, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   jinxian Xu, None; Xinglou Liu, None; Brendan Marshall, None; Zheng Dong, None; Ming Zhang, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 774. doi:
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      jinxian Xu, Xinglou Liu, Brendan Marshall, Zheng Dong, Ming Zhang; Latent Ocular Murine Cytomegalovirus (MCMV) exacerbates the development of Choroidal Neovascularization (CNV) in VEGF-Ahyper mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):774.

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

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Abstract

Purpose : Human cytomegalovirus (HCMV) promotes angiogenesis and this process contributes to many vascular diseases. However, it remains unclear if this virus plays any role in CNV. The purpose of this study was to investigate if latent ocular MCMV exacerbates the development of CNV in VEGF-Ahyper mice following systemic neonatal infection.

Methods : MCMV (50 pfu per mouse) or medium as control was peritoneally injected into VEGF-Ahyper or wild type (WT) 129 mice at <3 days after birth. Mice were sacrificed at intervals post infection (p.i.), and eyes and extraocular tissues were collected for analysis by plaque assay, PCR to detect viral gene expression, and for the presence of MCMV early antigen (EA). At 6 months p.i., some eyes were analyzed by fundus imaging and fluorescence angiography, by H&E staining, by real time RT-PCR for MCMV gene transcripts and by ELISA to determine protein levels of VEGF-A and other inflammatory factors.

Results : At day 14 p.i., replicating virus was detected in the lungs, salivary glands and eyes of infected mice. MCMV EA was observed in the choroid in all eyes from both VEGF-Ahyper and WT mice. No replicating virus was detected in the eyes and extra ocular tissues at 6 months p.i., although virus DNA was still detected in all eyes and extraocular tissues from both VEGF-Ahyper and WT mice. Expression of MCMV IE1 mRNA was detected only in latently infected eyes of VEGF-Ahyper mice (3/7), but not in eyes of WT mice (0/9). CNV lesions were observed in only 3/18 eyes from non-infected VEGF-Ahyper mice, whereas lesions were observed in 14 of 18 eyes from MCMV latently infected VEGF-Ahyper mice. MCMV-infected VEGF-Ahyper mice also exhibited an increased average lesion size and severity while CNV lesions were not observed in any eyes from infected or non-infected WT mice. Protein levels of CCL5, TGF-β1, IL6 and VEGF-A were all significantly higher in MCMV-infected VEGF-Ahyper mice, compared to non infected VEGF-Ahyper mice and infected or non-infected WT mice.

Conclusions : MCMV disseminates to and remains latent in the eyes following systemic infection of neonatal VEGF-Ahyper mice or WT 129 mice. Prior overexpression of VEGF-A induces activation of MCMV genes which in turn, promotes the production of inflammatory/angiogenetic factors and the development of CNV in latently infected VEGF-Ahyper mice.

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

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