July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Safety & effect of tivanisiran eye drops on ocular surface: corneal sensitivity, mucin production and proinflammatory mediator’s expression
Author Affiliations & Notes
  • Victoria Gonzalez
    Clinical, Sylentis, Spain
  • Beatriz Vargas
    Sylentis, Spain
  • Tamara Martinez
    Sylentis, Spain
  • Amor Guerra
    Sylentis, Spain
  • Veronica Ruz
    Sylentis, Spain
  • Ana Isabel Jimenez
    Sylentis, Spain
  • Footnotes
    Commercial Relationships   Victoria Gonzalez, Sylentis (E); Beatriz Vargas, Sylentis (E); Tamara Martinez, Sylentis (E); Amor Guerra, Sylentis (E); Veronica Ruz, Sylentis (E); Ana Isabel Jimenez, Sylentis (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6746. doi:
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      Victoria Gonzalez, Beatriz Vargas, Tamara Martinez, Amor Guerra, Veronica Ruz, Ana Isabel Jimenez; Safety & effect of tivanisiran eye drops on ocular surface: corneal sensitivity, mucin production and proinflammatory mediator’s expression. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6746.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Multifactorial nature of dry eye disease (DED) makes crucial the development of therapies to restore ocular surface homeostasis tackling simultaneously signs and symptoms.
Tivanisiran, a siRNA inhibitor of TRPV1 synthesis, showed in prior clinical trials to reduce conjunctival hyperemia and pain. Here, we used a model of New Zealand White (NZW) rabbits to study its effect on DED outcomes related to ocular surface safety and tear film quality

Methods : Toxicology studies were carried out in NZW rabbits and Beagle dogs for 6 and 9 months, respectively. Additionally, adult healthy NZW rabbits received 2.25% tivanisiran, vehicle or oxybuprocaine (anesthetic) twice daily (b.i.d) for 5 days. Corneal sensitivity was tested using a Cochet-Bonnet esthesiometer.
NZW rabbits received q.d 1.25% tivanisiran or vehicle for 28 days. Conjunctival impression cytology samples were taken to study tear quality parameters such as goblet cell density by laser scanning microscopy and MUC5A (mucin) and IL-1β (ocular inflammatory marker) expression by qRT-PCR. Differences between groups were assessed using paired Student’s t tests

Results : Tivanisiran showed a safe ocular toxicology profile with no effects on ophthalmic examinations, IOP or electroretinography at any time-point or studied dose. Tivanisiran showed a vehicle-like response, not inducing corneal sensitivity decline at any time-point, on the contrary, oxybuprocaine induced complete corneal anesthesia.
On Day 28, tivanisiran produced a 25% increase on mucin cloud density and a three-fold increase on MUC5A expression when compared to vehicle (p<0.05). A trend in the reduction of IL-1β expression was observed

Conclusions : The safe toxicology profile in the ocular surface together with the lack of tivanisiran anesthetic effect are key safety features in chronic therapies such as those for DED. It allows patient's awareness of possible ocular lesions such as corneal ulceration or scaring.
The positive effect of tivanisiran on mucin production and the trend on IL-1β reduction are key tear film quality and stability markers that may contribute to improve eye lubrication.
Overall, results help to further characterize the pharmacological profile of tivanisiran, acting not only by blocking hyperemia and pain pathways, but also as a secretagogue. These outcomes are expected to be replicated in the ongoing phase III trial

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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