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Updated: Aug 17, 2026
Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Infection of retinal neurons during murine cytomegalovirus retinitis
Ming Zhang1, Hua Xin, Penny Roon
1Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, 30912, USA.
Purpose:
Previous results suggest that retinal neurons are infected early during murine cytomegalovirus (MCMV) infection of the inner retina. The purposes of this study were to identify which retinal neurons are infected and to determine the routes by which MCMV spreads in the retina.
Methods:
Immunosuppressed (IS) BALB/c mice were inoculated with 5 x 10(3) PFU of MCMV (k181) through the supraciliary route. Injected eyes were collected at several times after inoculation, sectioned, and examined by electron microscopy and by staining for retinal cell antigens and for MCMV early (EA) or late (LA) antigen.
Results:
MCMV-infected cells were observed in the choroid and RPE by day 3 after infection (PI) and in the inner retina beginning at day 5 PI. At this time, many horizontal and bipolar cells were MCMV-antigen-positive but only rare MCMV-infected amacrine cells (glycine positive or gamma-aminobutyric acid [GABA] positive) or MCMV-infected ganglion cells (NF positive) were observed in the inner retina. At day 10 PI, most virus-infected cells were glial fibrillary acidic protein (GFAP)- and GABA-positive glia. Virions were observed by electron microscopy in the choroid, RPE, and inner nuclear layer of the retina. Although virions were observed in the endothelium of the retinal vessels and the nearby retinal cells, the endothelial cell lining of the retinal vessels remained intact. Both apoptotic cells and necrotic cells were seen in the inner retina.
Conclusions:
In the inner retina, horizontal and bipolar cells were the early (< or = day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Muller cells and within the inner retina horizontally through infected horizontal cells.
Insights
Murine cytomegalovirus (MCMV) primarily infects horizontal and bipolar cells early in the inner retina. The virus spreads via Muller cells and horizontal cells, causing cell death.
Area of Science:
- Ophthalmology
- Virology
- Neuroscience
Background:
- Previous research indicates retinal neurons are infected early during murine cytomegalovirus (MCMV) infection.
- The inner retina is a potential site for MCMV replication.
Purpose of the Study:
- To identify specific retinal neurons infected by MCMV.
- To determine the spread of MCMV within the retina.
Main Methods:
- Immunosuppressed mice were inoculated with MCMV via the supraciliary route.
- Eyes were collected and examined using electron microscopy and immunohistochemistry for MCMV antigens and retinal cell markers.
Main Results:
- MCMV infected cells were found in the choroid and RPE by day 3 post-infection (PI) and in the inner retina by day 5 PI.
- Early infection targeted horizontal and bipolar cells; later, glial cells (GFAP- and GABA-positive) were predominantly infected.
- Virions were observed in various retinal layers and vasculature, with evidence of both apoptotic and necrotic cells in the inner retina.
Conclusions:
- Horizontal and bipolar cells are early targets of MCMV in the inner retina (within 7 days PI).
- MCMV spreads from the RPE and photoreceptor layer to the inner retina via Muller cells.
- Intraretinal spread occurs horizontally through infected horizontal cells.
