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Porcine Corneal Tissue Explant to Study the Efficacy of Herpes Simplex Virus-1 Antivirals
Published on: September 20, 2021
Effect of antivirals on human corneal cells in vitro
M Berry1, D L Easty, E Declercq
1University of Bristol, Department of Ophthalmology, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.
Abstract:
Toxic effects of 10 antiviral substances [9-(2-hydroxyethoxymethyl)-guanine (ACV), E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), 5'-iodo-2'-deoxyuridine (IDU), phosphonoformic acid (PFA), 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and 5-trifluoromethyl-2'-deoxyuridine (TFT)] on uninfected human corneal cells were evaluated in two experimental models (undisturbed adherence and growth, and wound closure) under continuous drug exposure. The antiviral drugs were ranked in order of toxicity in each of the tests. The influence on toxicity of different experimental parameters such as initial cell density, length of exposure and trauma, was evaluated. There was significant interaction between toxicity and length of exposure. In undisturbed cultures antiviral compounds ranked as follows: PMEA = DHPG = ACV = CEDU < PFA = IDU = BVDU << HPMPC < TFT < HPMPA. Wounding or migration increased the apparent toxicity of the antiviral substances; trauma did not have an additional effect. In conditions where corneal epithelium is poorly populated and ulcerated, wound healing can be delayed by antiviral medication.
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