Infection of retinal neurons during murine cytomegalovirus retinitis

Ming Zhang, Hua Xin, Penny Roon, Sally S. Atherton

Research output: Contribution to journalArticle

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Abstract

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 × 103 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 γ-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 (≤ day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Müller cells and within the inner retina horizontally through infected horizontal cells.

Original languageEnglish (US)
Pages (from-to)2047-2055
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2005

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Cytomegalovirus Retinitis
Muromegalovirus
Retinal Neurons
Retina
Infection
Aminobutyrates
Retinal Vessels
Choroid
Cytomegalovirus Infections
Antigens
Virion
Glycine
Electron Microscopy
Viruses
Amacrine Cells
Glial Fibrillary Acidic Protein
Neuroglia
Ganglia
Endothelium
Endothelial Cells

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Infection of retinal neurons during murine cytomegalovirus retinitis. / Zhang, Ming; Xin, Hua; Roon, Penny; Atherton, Sally S.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 6, 01.06.2005, p. 2047-2055.

Research output: Contribution to journalArticle

Zhang, Ming ; Xin, Hua ; Roon, Penny ; Atherton, Sally S. / Infection of retinal neurons during murine cytomegalovirus retinitis. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 6. pp. 2047-2055.
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N2 - 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 × 103 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 γ-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 (≤ day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Müller cells and within the inner retina horizontally through infected horizontal cells.

AB - 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 × 103 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 γ-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 (≤ day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Müller cells and within the inner retina horizontally through infected horizontal cells.

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