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Elena Koudouna, Jarek Pedro Bacaret Cardenas, Pedro Javier Castro Pelaez, Marcel Y Avila; The effect of pH on the efficacy of Genipin corneal crosslinking. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2584.
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© ARVO (1962-2015); The Authors (2016-present)
Riboflavin/UVA corneal crosslinking (CXL) is the gold standard treatment for corneal ectasias, yet affected individuals with very thin corneas are not eligible for this treatment. While the recent introduction of genipin (GEN) as a natural CXL agent, has heralded a new era in the treatment of advanced corneal ectatic cases, there is little understanding on the underlying mechanisms involved in the GEN CXL and the parameters affecting this reaction. With the overarching aim of identifying the best delivery protocol for adequate GEN CXL, this study investigated the effect of pH on the efficacy of corneal CXL using a hydrolytic resistance model in porcine corneas.
A total of 88 porcine eyes were utilized in this study. An 8mm full-tissue-thickness biopsy was taken from the center of each cornea and corneas were randomly divided into four groups. Group 1 remained untreated. Groups 2, 3 and 4 received GEN 0.12% in diluents with varying pH (pH 5, pH 7.4 and pH 8.4, respectively) at a fixed treatment time of 1h at 37oC. Following treatment, corneas were submerged in 0.1M hydrochloric acid and incubated in a water bath at 37oC. Tissue morphology and anterior corneal disc diameter were evaluated at various time points post treatment. To evaluate the effect of each treatment on hydrolytic resistance, protein concentration was determined at each time point. Molecular modeling was used to gain mechanistic insights on the GEN-collagen interaction.
All GEN CXL groups showed higher hydrolytic resistance compared with untreated control, with corneas in group 4 demonstrating the greatest resistance. Likewise, corneas treated with GEN 0.12% in a diluent with a pH 8.4, maintained the biggest corneal disc diameter and preserved its form sufficiently compared to the other groups. Untreated corneas were most vulnerable to hydrolysis and were associated with markedly higher protein concentration in a shorter period of time. Computational modeling of the GEN-collagen CXL reaction supported that in a basic environment the reaction is more favorable.
Though there is still a long way to go before reaching clinical testing, GEN holds the promise of a potential alternative treatment for advanced cases of corneal ectasias. The efficacy of GEN CXL is pH dependent; with higher pH achieving greater CXL efficacy. Optimizing GEN delivery strategies would improve the GEN CXL outcomes and encourage its clinical application.
This is a 2020 ARVO Annual Meeting abstract.
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