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Physiologic and morphologic retinal changes induced by murine cytomegalovirus in BALB/c and severe combined immune
A Mizota1, D I Hamasaki, S S Atherton
1William L. McKnight Vision Research Institute, Miami, Florida.
Abstract:
Anterior chamber inoculation of murine cytomegalovirus (MCMV, 10(4) and 10(5) plaque-forming units) induced both physiologic and morphologic changes in the retinas of immunocompetent BALB/c and B- and T-cell-deficient severe combined immune deficient (SCID) mice. In BALB/c mice, the depression of the b-wave began on days 3-4 postinoculation (PI) and a further depression was recorded on day 7 PI. The electroretinograms (ERGs) remained depressed 1-2 weeks PI after which there was a recovery of the amplitude of the ERG 2-6 weeks later. The recovery was not complete; the maximum amplitude at 6 weeks was significantly lower than the preinoculation value. There was a greater loss in the amplitude than in the sensitivity of the ERG. Histologic examination of retinas with depressed ERGs showed swelling of the retinal pigment epithelium and distortion and shortening of the outer segment of the photoreceptors. With recovery of the ERG, there was normalization of the retinal histology. In SCID mice, the ERGs were extinguished, and there was no recovery. Histologically, there was a complete loss of the photoreceptors in the SCIDs, and electron microscopic examination showed viral particles in the retinal pigment epithelium and inner nuclear cells. These results demonstrate that MCMV can induce retinal pathology as reported in patients and show the importance of B- and T-lymphocytes in controlling the progression of this disease process.
Insights
Murine cytomegalovirus (MCMV) infection causes retinal damage in mice. Immune cells are crucial for controlling MCMV-induced retinal disease progression and recovery.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Murine cytomegalovirus (MCMV) is a model virus for studying human cytomegalovirus (HCMV) infections.
- Retinal pathology is a known complication of HCMV in humans.
Purpose of the Study:
- To investigate the effects of MCMV infection on retinal physiology and morphology in different mouse models.
- To elucidate the role of B and T lymphocytes in controlling MCMV-induced retinal disease.
Main Methods:
- Anterior chamber inoculation of MCMV in immunocompetent BALB/c and severe combined immune deficient (SCID) mice.
- Physiologic assessment using electroretinograms (ERGs).
- Morphologic assessment via histologic examination and electron microscopy.
Main Results:
- MCMV infection induced transient retinal dysfunction (b-wave depression) and structural changes in BALB/c mice, with partial recovery.
- SCID mice exhibited extinguished ERGs and complete photoreceptor loss, indicating a lack of immune control.
- Viral particles were identified in retinal pigment epithelium and inner nuclear cells of SCID mice.
Conclusions:
- MCMV infection can cause significant retinal pathology, mirroring findings in human patients.
- B and T lymphocytes play a critical role in controlling MCMV progression and enabling retinal recovery.