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Javier Andres Nahmias, Blake Hugo Fortes, Manuel Tapia, Tsung-Han Chou, Giovanni Luca Romano, Vittorio Porciatti, Luis E Vazquez; Effect of intravitreal injections of calcium channel blockers on retinal blood vessel caliber. Invest. Ophthalmol. Vis. Sci. 2017;58(8):739.
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© ARVO (1962-2015); The Authors (2016-present)
Calcium channel blockers (CCB) vasodilate blood vessels by decreasing vascular smooth muscle tone. We test the effects of intravitreal injections of nicardipine and verapamil on retinal blood vessel caliber using in vivo fluorescein angiography (FA).
6-month old C57/B6 mice were given intraperitoneal injections of 40uL of fluorescein and anesthetized with 150uL of ketamine/xylazine mixture. Baseline images were taken 15 minutes after injections to allow the fluorescein to reach steady-state circulation. FA images of the retinal blood vessels, centered on the optic disc, were taken utilizing a Multiline Heidelberg Retinal Angiography confocal scanning laser ophthalmoscope with a 55° lens, and sensitivity set to 60. After baseline imaging, 1uL intravitreal (IV) injections of 0.2mg/mL nicardipine or 2.5mg/mL verapamil were administered. FA images were taken 1 minute and 10 minutes after administration of drugs. The results were analyzed with ImageJ software using the area measurement within 4 consecutive bounding rectangles in 2 adjacent vessels to account for effects on retinal arteries and veins. Vessel regions selected for inclusion within bounding rectangles were those with ~80% pixel saturation. The ratio of post-injection area to pre-injection area obtained for each drug was compared using the paired t-test, with p<.05 indicating statistical significance.
Intravitreal injection of nicardipine resulted in a significant increase in retinal vessel caliber (1.32-fold of baseline; N=3, p<0.0001) within 1 minute of administration. Measurements taken 10 minutes post intravitreal nicardipine showed retinal vessel caliber returning to baseline. Similar results were observed at 1 minute after with intravitreal verapamil (1.50-fold of baseline; N=3, p<0.0001), vessel caliber significantly decreased 10 minutes after intravitreal verapamil (-1.13-fold of baseline; N=3, p=0.0007).
Preliminary data supports the use of intravitreal administration of nicardipine and verapamil to increase vessel caliber. However, the short duration of action is unlikely to have a significant effect in retinal perfusion in chronic conditions such as glaucoma. Formulations or pharmacological agents with long-lasting vasodilatory effects will be tested in future studies.
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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