July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The Endothelin Receptor Antagonist Macitentan Attenuates Vasoconstrictive Effects of Endothelin-1 following Intravitreal Administration in Rodents
Author Affiliations & Notes
  • Raghu R Krishnamoorthy
    Pharmacology and Neuroscience, NTERI, UNT Health Science Ctr, Fort Worth, Texas, United States
  • Wei Zhang
    Pharmacology and Neuroscience, NTERI, UNT Health Science Ctr, Fort Worth, Texas, United States
  • Sai Chavala
    Pharmacology and Neuroscience, NTERI, UNT Health Science Ctr, Fort Worth, Texas, United States
  • Dorota L Stankowska
    Pharmacology and Neuroscience, NTERI, UNT Health Science Ctr, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Raghu Krishnamoorthy, None; Wei Zhang, None; Sai Chavala, None; Dorota Stankowska, None
  • Footnotes
    Support  NIH grant EY028179
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 40. doi:
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      Raghu R Krishnamoorthy, Wei Zhang, Sai Chavala, Dorota L Stankowska; The Endothelin Receptor Antagonist Macitentan Attenuates Vasoconstrictive Effects of Endothelin-1 following Intravitreal Administration in Rodents. Invest. Ophthalmol. Vis. Sci. 2019;60(9):40.

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

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Abstract

Purpose : Our previous studies demonstrated that administration of the endothelin receptor antagonist, macitentan, attenuated RGC loss in rats with elevated IOP. The purpose of this study was to determine if macitentan could block vasoconstrictive changes following intravitreal endothelin-1 (ET-1) administration in rats.

Methods : Adult retired breeder male and female Brown Norway rats were intravitreally injected in one eye with either 4 microliters of 500 micromolar ET-1 or its vehicle. Imaging of the retinal vasculature was carried out for 5, 10, 15, 20 and 30 minutes following ET-1 administration. In another set of experiments, adult male and female Long Evans rats were either untreated or treated with macitentan (5 mg/kg body wt) for three alternate days. Following the treatment, the rats were intravitreally injected in one eye with 4 microliters of 500 micromolar ET-1 and the retinal vasculature was imaged in a Micron IV retinal imaging system.

Results : ET-1 administration produced rapid vasoconstrictive effects in retinal arteries that occurred 5 min after intravitreal administration and recovery was observed 20 min. post-injection.The vasoconstrictive effect was not observed in rats intravitreally injected with the vehicle. Rats treated with macitentan in the diet abrogated the ET-1 mediated vasoconstrictive effects or delayed its onset.

Conclusions : Blocking both ETA and ETB receptors by oral administration of the endothelin receptor antagonist, macitentan, may inhibit ischemia by attenuating vasoconstriction. Endothelin receptor antagonists could potentially act through both vascular and cellular mechanisms to promote neuroprotection in glaucoma.

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

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