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Abstract
Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the diffusion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen’s egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the different antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 °C in darkness and it is not an irritant to the eye. The diffusion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.
Highlights
Oxidative stress was defined by Helmut Sies as “a change in the prooxidant-antioxidant balance in favor of the former” [1]
The results obtained in this study provide interesting results for the development of ocular formulations of GSH as an antioxidant for the treatment of eye diseases
The results from this study have revealed that the GSH solution is not an irritant to ocular mucosa and is stable in solution preserved at 4 ◦C in darkness for up to one month and the incorporation of vitamin C (Vit C) into this solution does not lengthen its preservation
Summary
Oxidative stress was defined by Helmut Sies as “a change in the prooxidant-antioxidant balance in favor of the former” [1]. Oxidative stress stimulates the production of highly reactive oxygen species (ROS), potentially leading to cellular damage. Our eyes are especially susceptible to oxidative stress because they are greatly exposed to sunlight and atmospheric oxygen [2]. Alterations in the cellular redox state within the eye are believed to contribute to the pathogenesis of many ocular diseases [3]. Ocular tissues have several intrinsic antioxidants to overcome the oxidative stress generated as a result of normal cell metabolism. The two key antioxidants in the eye are glutathione (GSH) and vitamin C (Vit C) [4]. While ascorbic acid (Vit C) is found in the corneal epithelium, GSH is found mainly in the lens [5,6]
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