Real-Time Measurement of Antiglaucoma Drugs in Porcine Eyes Using Boron-Doped Diamond Microelectrodes

The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial fo...

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Published inACS sensors Vol. 9; no. 2; pp. 781 - 788
Main Authors Ogata, Genki, Yoneda, Mao, Ogawa, Risa, Hanawa, Ai, Asai, Kai, Yamagishi, Reiko, Honjo, Megumi, Aihara, Makoto, Einaga, Yasuaki
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 23.02.2024
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ISSN2379-3694
2379-3694
DOI10.1021/acssensors.3c02088

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Abstract The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC–MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.
AbstractList The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC-MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC-MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.
The primary treatment for glaucoma, the most common cause of intermediate vision impairment, involves administering ocular hypotensive drugs in the form of topical eye drops. Observing real-time changes in the drugs that pass through the cornea and reach the anterior chamber of the eye is crucial for improving and developing safe, reliable, and effective medical treatments. Traditional methods for measuring temporal changes in drug concentrations in the aqueous humor employ separation analyzers such as LC–MS/MS. However, this technique requires multiple measurements on the eyes of various test subjects to track changes over time with a high temporal resolution. To address this issue, we have developed a measurement method that employs boron-doped diamond (BDD) microelectrodes to monitor real-time drug concentrations in the anterior chamber of the eye. First, we confirmed the electrochemical reactivity of 13 antiglaucoma drugs in a phosphate buffer solution with a pH of 7.4. Next, we optimized the method for continuous measurement of timolol maleate (TIM), a sympathetic beta-receptor antagonist, and generated calibration curves for each BDD microelectrode using aqueous humor collected from enucleated porcine eyes. We successfully demonstrated the continuous ex vivo monitoring of TIM concentrations in the anterior chambers of these enucleated porcine eyes. The results indicate that changes in intracameral TIM concentrations can be monitored through electrochemical measurements using BDD microelectrodes. This technique holds promise for future advancements in optimizing glaucoma treatment and drug administration strategies.
Author Yoneda, Mao
Einaga, Yasuaki
Ogata, Genki
Honjo, Megumi
Ogawa, Risa
Asai, Kai
Yamagishi, Reiko
Aihara, Makoto
Hanawa, Ai
AuthorAffiliation Department of Chemistry
Department of Ophthalmology, School of Medicine
The University of Tokyo
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Keywords eye drops
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glaucoma
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Title Real-Time Measurement of Antiglaucoma Drugs in Porcine Eyes Using Boron-Doped Diamond Microelectrodes
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