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A. Heiligenhaus, J. Li, S. Wasmuth, M. Hennig, D. Bauer; Intravitreal Tumor Necrosis Factor-alpha Antisense-Oligonucleotides Improve Herpes Simplex Virus Induced Acute Retinitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):737.
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© ARVO (1962-2015); The Authors (2016-present)
In the murine model of herpes simplex virus (HSV)-1 induced acute retinal necrosis (von Szily model), TNF-α is expressed in the contralateral eye during the development of disease. This study analyzed the influence of an intravitreal injection of antisense-oligonukleotides (ASON) directed against TNF-α mRNA on the contralateral retinitis.
The distribution of FITC-labeled TNF-α-ASON was determined after intravitreal injection. Paraffin sections from eyes, regional lymph nodes (rln) and spleens were investigated by fluorescence microscopy, and single cell suspensions from rln and spleens were analyzed by flow cytometry. In BALB/c mice, 1x105 PFU of HSV-1 (KOS) were injected on day 0 into the anterior chamber of the right eyes. On day +7, TNF-α-ASON were injected into the vitreous of the contralateral eyes. Control-ASON (CON) or buffer were applied in control mice. The contralateral eyes were followed clinically for the presence of disease, and were studied by histopathology. In the contralateral eyes, intraocular TNF-α expression and virus replication were analyzed. The HSV-1-antigen specific DTH was determined on day +10.
Two days after intravitreal FITC-ASON injection, FITC-positive cells were found in the inner retina, ciliary body and iris. By flow cytometry analysis, few FITC-positive cells were found in the rln and spleen. Following the TNF-α-ASON injection in the contralateral eyes, the incidence and severity of retinitis, the inflammatory cell infiltration in the choroid and retina, and the intraocular TNF-α expression were reduced as compared to the control groups. The viral titers in the contralateral eyes and the HSV-1 specific DTH-reaction did not differ between the groups.
TNF-α-ASON were found in retinal and uveal cells after intravitreal injection. The incidence and severity of experimental HSV-1 induced acute retinitis in the contralateral eyes improved after treatment, while the systemic immune response was not altered.
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