Abstract
Purpose :
Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice can spread to the eye with subsequent establishment of latency in the choroid and RPE. MCMV latency in the choroid/RPE was associated with the upregulation of several inflammatory/angiogenic factors, and the development of AMD-like pathology in a progressive manner, including loss of choroidal capillaries, deposits in basal aspects of the RPE, degeneration of RPE and photoreceptors and eventually, choroidal neovascularization (CNV) in later life. The purpose of this study was to determine if the development of AMD-like pathology is associated with reactivation of viral gene expression.
Methods :
MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 8 and 18 months p.i., optical coherence tomography (OCT) examinations were performed to monitor the integrity of retinal structure using an Envisu R2210 system. MCMV or medium injected mice were sacrificed and eyes were collected and examined by realtime-RT-PCR for expression of 26 virus genes related to latency.
Results :
The mean retinal thickness in MCMV latently infected aged mice was significantly lower than in eyes of age matched controls at both 8 and 18 months p.i. Severe photoreceptor degeneration (including disappearance of the entire outer nuclear layer in some areas) and CNV lesions (average 2 per eye) were observed in 7 and 4 eyes respectively of 26 total eyes. Among 26 genes studied, 17 were expressed in some eyes from MCMV infected mice at both 8 and 18 months p.i. These included immediate early genes (IE1 and IE3) and genes functioning in anti-apototic (M37, M38.5, MM41 and M45) and immune evasion (M04, M138, M152). In addition, 2 genes (M18 and M82) were expressed only in aged eyes at 18 months p.i.
Conclusions :
Virus gene expression during MCMV ocular latent infection may significantly alter homeostasis of the latently infected cell and the surrounding cellular environment and therefore induce the development of AMD-like pathology.
This is a 2021 ARVO Annual Meeting abstract.