Mark A Fields

Georgia Health Sciences University, Augusta, Georgia, United States

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Publications (4)15.29 Total impact

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    ABSTRACT: After uniocular anterior chamber (AC) inoculation with HSV-1, the anterior segment of the injected eye becomes inflamed and infected; however, virus does not spread from the anterior segment and infect the retina of the injected eye. The purpose of this study was to identify early infiltrating cells and to determine whether infiltrating cells produce interferon (IFN)gamma. Euthymic, female, BALB/c mice were injected in one AC with 3 x 10(4) PFU of HSV-1 (KOS) in a volume of 2 microL. Mice from each group were killed at 12, 24, 36, 48, and 72 hours post injection (pi), the eyes were enucleated, and frozen sections were stained with antibodies specific for IFNgamma, Mac-1 (CD11b), CD49b, F4/80, CD4, CD8, and CD11c. The same antibodies were also used to stain single-cell suspensions of ocular cells for flow cytometry. In the anterior segment of the injected eye, the ciliary body, and iris were virus infected and inflamed, and infiltrating cells increased throughout the period of observation. Mac-1(+), CD49b(+), and F4/80(+) cells colocalized with IFNgamma in the anterior segment as early as 12 hours pi, and the percentage of Mac-1(+) cells increased in the injected eye beginning at 24 hours pi and continued to 72 hours pi. Taken together, these results demonstrate that Mac-1(+) cells are important IFNgamma-producing cells in the injected eye before day 3 and suggest that the IFNgamma produced by these cells is involved in inhibition of anterior to posterior spread of virus in the injected eye.
    Investigative ophthalmology & visual science 06/2009; 50(5):2269-75. DOI:10.1167/iovs.08-2874 · 3.66 Impact Factor
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    Mark A Fields · Mei Zheng · Pam Wall · Scott Oberg · Sally S Atherton
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    ABSTRACT: Tumor necrosis factor alpha (TNF-alpha) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-alpha affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-alpha constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-alpha recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-alpha expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6beta rescue-, or KOS6beta-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-alpha has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.
    Journal of Virology 06/2008; 82(10):5068-78. DOI:10.1128/JVI.00082-08 · 4.65 Impact Factor
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    ABSTRACT: To determine whether infiltrating polymorphonuclear leukocytes PMNs play a role in preventing early direct anterior-to-posterior spread of herpes simplex virus (HSV)-1 and/or in preventing the spread of HSV-1 from the brain back to the retina of the injected eye after anterior chamber (AC) inoculation. BALB/c mice were treated with monoclonal antibody RB6-8C5 (Gr-1) against PMNs or control IgG and inoculated with HSV-1. In Gr-1-treated mice, PMNs were depleted in the peripheral blood and in the HSV-1-infected eye. More virus (2-3 logs) was recovered from the inoculated eye of Gr-1 antibody-treated mice than from control mice. Immunohistochemistry revealed disseminated virus-infected cells in the junction between the anterior and the posterior segment and also in the posterior segment of the HSV-1-inoculated eye in Gr-1-treated mice. In control IgG-treated mice, virus-infected cells were observed only within the AC. More virus (3 logs) was recovered from the contralateral suprachiasmatic nucleus (SCN), and increased virus staining was observed in the ipsilateral optic nerve of Gr-1-treated mice compared with control mice. In Gr-1-treated mice, the central retina was virus-infected in a patchy fashion beginning on day 7 post infection (pi), and the infection progressed to involve the entire retina. Since both direct anterior-to-posterior spread of virus and spread via the optic nerve occurred in PMN-depleted mice, these results suggest that PMNs play an important role both in limiting intraocular spread of virus in the injected eye and in controlling spread of the virus from the brain into the optic nerve and retina of the injected eye.
    Investigative ophthalmology & visual science 06/2008; 49(9):4018-25. DOI:10.1167/iovs.08-1914 · 3.66 Impact Factor
  • Mark Fields · Mei Zheng · Ming Zhang · Sally S Atherton
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    ABSTRACT: After uniocular anterior chamber (AC) inoculation of herpes simplex virus type 1 (HSV-1), virus and TNF alpha (TNF-alpha) are detected in the suprachiasmatic nuclei (SCN). The goal of this study was to investigate the role of TNF-alpha and macrophages in the brain of HSV-1-infected BALB/c mice. Mice were treated with thalidomide for TNF-alpha inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). The location of HSV-1, macrophages, and TNF-alpha was determined by fluorescence immunohistochemistry and the titer of virus was determined by plaque assay. Inhibition of TNF-alpha was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and depletion of macrophages was assessed by flow cytometry. In thalidomide-treated mice, TNF-alpha RNA levels were reduced in the SCN. Both SCN were infected by day 5 post inoculation (p.i.) and the titer of virus in the SCN contralateral to the side of injection was increased. The number of splenic macrophages was significantly reduced in clodronate-treated mice compared with controls. In macrophage-depleted mice, both SCN were infected at day 6 p.i. and the titer of virus in the SCN of these mice was increased at days 6 and 7 p.i. compared with controls. The titer of virus in the contralateral (uninoculated) eye of macrophage-depleted mice was increased at day 7 p.i. Fewer F4/80+ cells were observed in the SCN of macrophage-depleted mice. The results of these studies suggest that TNF-alpha plays a role in limiting virus replication in the SCN of euthymic BALB/c mice and that one source of TNF-alpha is macrophages.
    Journal of NeuroVirology 01/2007; 12(6):443-55. DOI:10.1080/13550280601039030 · 3.32 Impact Factor

Publication Stats

22 Citations
15.29 Total Impact Points


  • 2007–2009
    • Georgia Health Sciences University
      • Department of Cellular Biology & Anatomy
      Augusta, Georgia, United States