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Apoptosis in the retina during MCMV retinitis in immunosuppressed BALB/c mice
1Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.
Background:
Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection observed in immunosuppressed (IS) adult and pediatric patients. Due to the species restriction of the cytomegaloviruses, mice infected with murine CMV (MCMV) have been used to study the pathogenesis of CMV retinitis.
Objectives:
The objectives of this study were to determine if retinal glial cells are the targets of MCMV infection and to determine which cells in the retina become apoptotic following inoculation of MCMV via the supraciliary route.
Study Design:
Adult female BALB/c mice were IS with methylprednisolone; one half of the mice were injected with MCMV and one half of the mice were injected with an equivalent volume of tissue culture medium via the supraciliary route. Animals were sacrificed and frozen sections of eyes were stained for MCMV early antigen, RPE65, CD45 or TUNEL; additional slides were double stained with combinations of the above reagents.
Results And Conclusions:
The results indicate that most apoptotic cells in the retina were not virus infected, most apoptotic cells were not infiltrating CD45 positive leukocytes, and retinal glial cells were infected with MCMV but only late in infection. Together, these results suggest that retinal cells that undergo apoptosis during MCMV infection are neurons and that apoptosis of uninfected bystander cells is an important component of the pathogenesis of CMV retinitis.
Insights
Murine cytomegalovirus (MCMV) causes apoptosis in retinal neurons, not just infected cells. This bystander effect is key to understanding cytomegalovirus (CMV) retinitis pathogenesis in immunosuppressed patients.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunosuppressed individuals.
- Murine cytomegalovirus (MCMV) is used as a model to study CMV retinitis due to species specificity.
Purpose of the Study:
- To identify retinal glial cells as MCMV targets.
- To determine which retinal cells undergo apoptosis after MCMV inoculation via the supraciliary route.
Main Methods:
- Immunosuppressed (IS) BALB/c mice were inoculated with MCMV or control medium via the supraciliary route.
- Eye sections were stained for MCMV antigen, RPE65, CD45, and TUNEL, with double staining for combined analysis.
Main Results:
- Most apoptotic retinal cells were not infected with MCMV.
- Apoptotic cells were predominantly uninfected neurons, not infiltrating leukocytes.
- Retinal glial cells were infected with MCMV, but only late in the infection.
Conclusions:
- Apoptosis of uninfected bystander cells, primarily neurons, is crucial in MCMV retinitis pathogenesis.
- This finding advances the understanding of CMV retinitis mechanisms in immunosuppressed patients.
