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M. Berdugo-Polak, I. V. Larsen, C. Abadie, L. Kowalczuk, E. Touchard, J. D. Nelson, P. P. Elena, C. R. Brandt, F. Behar-Cohen, J.-M. Combette; Ocular Distribution and Spectrum of Activity of a Fully Human Anti-Herpes Simplex Virus IgG Fab Fragment, Following Topical Application. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1991.
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To evaluate ocular biodistribution of an anti-HSV human IgG Fab fragment (AC-8, 53 kDa), following topical administration onto the rat eye, and to determine the spectrum of activity against HSV-1 ocular isolates.
An AC-8 solution (10-1000 µg/mL) was instilled 5 times/day for 1-4 days on rat eyes with normal or de-epithelialized corneas. At 1, 6, and 24 hours after administration, the eyes were processed for either IHC or ELISA assay. Antiviral activity was determined for 13 HSV strains using a yield reduction assay.
After repeated instillation, AC-8 was found in the corneal epithelium, anterior stroma, sub-epithelial stromal cells and retinal glial cells. The AC-8 signal was more intense at the limbus and peripheral cornea suggesting a trans-limbal and trans-scleral intraocular penetration. De-epithelialization did not change the AC-8 distribution profile but the newly-formed epithelium was intensely labeled. Sub-conjunctival injection resulted in a much higher AC-8 signal in the anterior segment and retina. Using either instillation of AC-8 or sub-conjunctival injection, levels consistent with anti-viral activity were found in the corneal epithelium. The EC50 values ranged from 0.01 to 0.04 µg/mL.
Topical instillation of an anti-HSV Fab can be used on intact and ulcerated cornea. It does not alter re-epithelialization. The intracellular uptake and broad inhibition suggests that AC-8 could feasibly exert a protection against HSV ocular infection.
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