April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
EFFECT OF HYDROGEN SULFIDE-RELEASEING COMPOUNDS ON AQUEOUS HUMOR DYNAMICS
Author Affiliations & Notes
  • Ya Fatou Njie-Mbye
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Jenaye Robinson
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Chinonso Ezeudu
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Leah Mitchell
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Madhura Kulkarni-Chitnis
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Catherine A Opere
    Pharmacy Sciences, Creighton University, Omaha, NE
  • Sunny E Ohia
    Pharmaceutical Sciences, Texas Southern University, Houston, TX
  • Footnotes
    Commercial Relationships Ya Fatou Njie-Mbye, None; Jenaye Robinson, None; Chinonso Ezeudu, None; Leah Mitchell, None; Madhura Kulkarni-Chitnis, None; Catherine Opere, None; Sunny Ohia, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2890. doi:
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      Ya Fatou Njie-Mbye, Jenaye Robinson, Chinonso Ezeudu, Leah Mitchell, Madhura Kulkarni-Chitnis, Catherine A Opere, Sunny E Ohia; EFFECT OF HYDROGEN SULFIDE-RELEASEING COMPOUNDS ON AQUEOUS HUMOR DYNAMICS. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2890.

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

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Abstract

Purpose: The presence of biosynthetic enzymes for hydrogen sulfide (H2S) production coupled with reports of its pharmacological action in ocular tissues, suggests a potential role for this novel gaso-transmitter in intraocular pressure (IOP) regulation. In this study, we investigated the effects of H2S (generated from donor, sodium hydrosulfide (NaHS), and substrate, L-cysteine) on IOP and aqueous humor (AH) outflow facility.

Methods: A single dose of H2S-releasing compounds, NaHS and L-cysteine or vehicle (normal saline) was topically applied to each eye of New Zealand Albino rabbits. IOP was measured with a pneumatonometer at baseline and at regular intervals (30 - 120 minutes) until baseline IOP was stable. For AH outflow studies, porcine ocular anterior segment explants with intact trabecular meshwork were perfused with DMEM maintained at 37°C, 5% CO2 and constant pressure of 7.35 mmHg. Stabilized explants were exposed to NaHS and L-cysteine. Explants were also treated with the KATP channel antagonist glibenclamide and H2S biosynthetic enzyme inhibitors, aminooxyacetic acid (AOA), or proparglyglycine (PAG).

Results: NaHS (1%) elicited a significant time-dependent (p < 0.001) reduction in IOP in treated eyes that reached a maximum at 3 hours and remained sustained for 6 hours. L-cysteine (5%) also reduced IOP for up to 7 hours, achieving a maximal IOP reduction of 28.8% (p<0.01) after 3 hours. Moreover, both compounds elicited a parallel but smaller reduction of IOP in contralateral, vehicle-treated eye. Interestingly, L-cysteine (1 nM - 1μM) caused a dose-dependent increase in AH outflow from porcine anterior segment explants, reaching a maximal effect at 100 nM [153 ± 7.2% of basal (mean ± SE)]. The effect of L-cysteine (100 nM) on AH outflow was completely attenuated by AOA (30 μM) and PAG (1 mM). NaHS (100 nM - 10 µM) also produced a concentration-dependent increase in AH outflow, reaching a maximal effect at 10 μM. In addition, the enhancement of outflow caused by both NaHS (10 μM) and L-cysteine (100 nM) was inhibited significantly (p < 0.01) by glibenclamide (100 µM).

Conclusions: We conclude that compounds that produce H2S can lower IOP in normotensive rabbits. In porcine eyes, the H2S-induced decrease in IOP is due to an increase in AH outflow via the trabecular meshwork. Furthermore, the H2S-induced increase in AH outflow is dependent upon the intramural biosynthesis of H2S and, is mediated by KATP channels.

Keywords: 427 aqueous • 568 intraocular pressure • 633 outflow: trabecular meshwork  
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