Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

Abstract

Purpose: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-Nacetylcysteine(SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at finalconcentrations 1.0 and 10.0 mM. Methods: Ex vivo GSNO and SNAC toxicities were clinically and histologicallyanalyzedusing freshly excised pig eyeballs. In vivo experiments were performedwith 20 albino rabbits which were randomized into 4 groups (5 animals each):Groups 1 and 2 received instillations of 150 μL of aqueous HPMC solution containingGSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4received instillations of 150 μL of aqueous HPMC solution-containing SNAC 1.0 and10.0 mM, respectively, in one of the eyes. The contralateral eyes in each groupreceived aqueous HPMC as a control. All animals underwent clinical evaluationon a slit lamp and the eyes were scored according to a modified Draize eye testand were histologically analyzed. Results: Pig eyeballs showed no signs of perforation, erosion, corneal opacity orother gross damage. These findings were confirmed by histological analysis. Therewas no difference between control and treated rabbit eyes according to the Draizeeye test score in all groups (p>0.05). All formulations showed a mean score under1 and were classified as "non-irritating". There was no evidence of tissue toxicityin the histological analysis in all animals. Conclusion: Aqueous HPMC solutions containing GSNO and SNAC at concentrationsup to 10.0 mM do not induce ocular irritation.