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Ana Isabel Jimenez, Covadonga Pañeda, Tamara Martinez, Amor Guerra, Nuno Fonseca, Susana Monteiro, Cristian Salvador, Jesus Merayo-Lloves, Ignacio Alcalde, Veronica Ruz, Victoria Gonzalez; Efficacy of SYL1001 in different animal models of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):458.
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To assess the potential role of SYL1001 in several animal models of Dry Eye Disease and to extrapolate possible uses in man.
SYL1001 is a compound based on RNA interference technology under advanced clinical development for the treatment of Dry Eye Disease. SYL1001 targets Transient Receptor Protein Vanilloid type 1 (TRPV1), a cation channel present in the neuronal terminals that innervate the cornea. Down regulation of this channel has shown to reduce eye discomfort in patients suffering from Dry Eye Disease (measured using the VAS scale) as well as conjunctival hyperemia staining. The primary objective of this set of studies was to assess different outcome measures in animal models of Dry Eye Disease and to compare the efficacy of SYL1001 to that of other treatments currently available in the clinic. For this purpose we used a mouse model in which dry eye symptoms were induced in C57BL/6N mice by exposing them to a controlled environment (relative humidity <25%, airflow 15L/min, temperature 20-22°C) and systemic scopolamine administration (0.5 mg/72h) for 7 days. To further elucidate the possible actions of SYL1001 in dry eye disease, a mouse model of dry eye induced by corneal ablation was used. In this model the innervation of the central cornea is completely severed, causing a reduction in tear production.
RNA interference works in a sequence dependent manner, reducing specifically the expression of the gene against which the compound is designed. Prior to conducting experiments in murine models we analyzed if SYL1001 was active in mouse cells by transfecting the compound into C2C12 cell line. The compound was shown to reduce TRPV1 mRNA levels in these cells with an efficacy comparable to the one observed in human cells. Treatment with SYL1001 dose-dependently increased the number of MUC5A+ positive cells in the cornea of a mouse model of scopolamine-induced dry eye disease; this effect was equivalent to that of cyclosporine. In the corneal-ablation model, treatment with SYL1001 improved the rate of corneal wound healing and haze scoring. In addition, SYL1001 increased tear production if the first days post-ablation.
SYL1001, a RNA compound under development for the treatment of signs and symptoms of dry eye disease has shown to improve several outcomes in different models of dry eye disease. This further supports the development of the compound for several forms of dry eye disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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