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S. S. Atherton, M. A. Fields; Increased Replication and Destruction in the Retina of Eyes Infected With a TNF- Expressing Recombinant of HSV-1. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2827.
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Our previous studies have shown that (1) TNF-α plays a role in modulating spread of HSV-1 in the SCN and (2) in the uninoculated eye, overexpression of TNF-α after uniocular anterior chamber (AC) inoculation of a TNF-α producing recombinant of HSV-1 leads to increased leukocytic infiltration and increased levels of inflammatory mediators in the uninoculated eye. These studies continued our examination of the role of TNF-α in the pathogenesis of HSV-1 retinitis.
BALB/c mice were injected in one AC with 2 × 104 PFU of KOSTNF, the TNF-α recombinant virus (group 1), with a recombinant containing the pCI plasmid DNA alone (group 2), with the parental virus (group 3), or with a rescued virus containing the lacz gene (group 4). Fluorescence microscopy and hematoxylin and eosin staining were used to identify virus-infected cells in the uninjected eye and to assess the extent of retinal destruction on days 1-7 p.i. The titer of virus in the uninjected eye was determined by plaque assay. Leukocyte infiltration was evaluated by fluorescence microscopy and flow cytometry.
In the uninjected eye of KOSTNF -infected mice, there were more viral antigen positive cells and increased numbers of leukocytes. There was earlier microscopic evidence of retinal infection and destruction in these mice. In addition, the titer of virus in the uninjected eye was significantly increased in KOSTNF-infected mice on day 7 p.i. compared with KOSpCI, (group 2), with parental KOS6β infected mice (group 3), or with the KOS6βrescue virus (group 4) (6.03 × 103, 1.82 × 102, 2.09 × 102, and 1.00 × 102 PFU, respectively, p<0.05).
These results suggest that although TNF-α plays a protective role during the CNS phase of this infection, simply increasing the amount of this modulator by overproduction does not have a beneficial effect in the retina. Therefore, caution should be exercised in attempting to modulate levels of TNF-α in the eye/retina, since such modulation may have a deleterious, rather than a protective, effect.
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