The Effect of Ascorbic Acid (Vitamin C) on Transepithelial Corneal Cross-Linking in Rabbits

Koç, Mustafa; Bostanci, Başak; Demirel, Özlem; Genc, Feyza; Tekin, Kemal; Koban, Yaran; Dinçel, Aylin Sepici; Şen, Murat; Yılmazbaş, Pelin

doi:10.1089/jop.2017.0025

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…Both TRAM-34 and ascorbic acid have previously been shown to be safe and well-tolerated when administered to the cornea topically with minimal effects or cellular toxicity [ 24 , 25 , 31 – 34 ]. In this study, we investigate the hypothesis that a dual formulation of topical TRAM-34 and ascorbic acid will be well-tolerated, safe, and effective at reducing corneal haze after wounding in an in vivo model.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo

et al. 2022

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Corneal injury and aberrant wound healing commonly result in corneal fibrosis and subsequent vision loss. Intermediate-conductance calmodulin/calcium-activated K+ channels (KCa3.1) have been shown to promote fibrosis in non-ocular and ocular tissues via upregulation of transforming growth factor beta (TGFβ). TRAM-34 is a selective inhibitor of KCa3.1 and reduces fibrosis by downregulation of TGFβ-induced transdifferentiation of stromal fibroblasts to myofibroblasts. Ascorbic acid has been demonstrated to be effective in promoting corneal re-epithelialization and reduction of neovascularization via anti-VEGF and anti-MMP mechanisms. This study evaluates tolerability and efficacy of a novel combination of TRAM-34 (25μM) and ascorbic acid (10%) topical treatment for corneal fibrosis using an established in vivo rabbit model and conducting clinical eye examinations. Markers of corneal fibrosis were evaluated in all corneas at study endpoint via histopathology, immunofluorescence, and quantitative real-time PCR. The eyedrop treated eyes showed significantly improved clinical outcomes based on modified McDonald Shadduck scores, reduction of clinical haze on Fantes scores, and reduction of central corneal thickness (CCT). At cellular and molecular levels, eyedrop treatment also significantly reduced expression of alpha smooth muscle actin (α-SMA) mRNA and protein, collagen III mRNA, and fibronectin mRNA compared to non-treated eyes. Our study suggests that a tested new bimodal eyedrop is well tolerated and effectively reduces corneal fibrosis/haze in rabbits in vivo.

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Section: Introductionmentioning

confidence: 99%

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo

et al. 2022

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“…(Koller et al, 2009;Shalchi et al,2015) To avoid debridement of the epithelium, transepithelial applications of Rf have been intensively studied, with many different methods having been tested in the lab and clinic. Most successful approaches rely on the addition of chemicals that break down the epithelial barrier, such as benzalkonium chloride (BAK), (Akbar et al, 2017;Aldahlawi et al, 2016;Chow et al, 2018;Gore et al, 2015a;Hayes et al, 2016;Lim et al, 2017) the addition of vitamins E or C, (Koc et al, 2017;Ostacolo et al, 2013) or iontophoresis. (Cassagne et al, 2016;Gore et al, 2015b;Mastropasqua et al, 2014;Vinciguerra et al, 2014) Whatever the method of Rf application, however, transepithelial UVA CXL has yet to reproduce the results of traditional UVA CXL.…”

Section: Introductionmentioning

confidence: 99%

Nonlinear optical crosslinking (NLO CXL) for correcting refractive errors

Bradford

Mikula

Juhász

et al. 2020

Experimental Eye Research

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Ultraviolet A (UVA) light-based photoactivation of riboflavin (Rf) to induce corneal crosslinking (CXL) and mechanical stiffening is now a well-known treatment for corneal ectasia and Keratoconus that is being used in a topographically guided photorefractive intrastromal CXL (PiXL) procedure to treat low degrees of refractive errors. Alternative approaches for non-invasive treatment of refractive errors have also been proposed that use femtosecond lasers (FS) that provide much faster, more precise, and safer results than UVA CXL. One such treatment, nonlinear optical crosslinking (NLO CXL), has been able to replicate the effects of UVA CXL, while producing a smaller area of cellular damage and requiring a shorter procedure time. Unlike UVA CXL, the treatment volume of NLO CXL only occurs within the focal volume of the laser, which can be placed at any depth and scanned into any pattern for true topographically guided refractive correction. This review presents our experience with using FS lasers to photoactivate Rf and perform highly controlled corneal CXL that leads to mechanical stiffening and changes in corneal shape.

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“…Vit C is one of the most important antioxidants in the cornea [ 7 ] and as it is neither synthesized nor stored in the human body, dietary intake is essential to maintain its adequate levels. Vit C is also found in high concentrations in the aqueous humor [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases

et al. 2020

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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.

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The Effect of Ascorbic Acid (Vitamin C) on Transepithelial Corneal Cross-Linking in Rabbits

Abstract: Systemic vitamin C does not appear to decrease effectiveness of transepithelial corneal CXL. Therefore, there is no reason to stop or reduce vitamin C supplementation before corneal CXL therapy.

Cited by 7 publications

References 23 publications

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo

Nonlinear optical crosslinking (NLO CXL) for correcting refractive errors

Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases

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