June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Regulation of Mammalian Sympathetic Neurotransmitter Release and Intraocular Pressure by Hydrogen Sulfide Donor, GYY 4137
Author Affiliations & Notes
  • Ankita Salvi
    Creighton University, Omaha, NE
  • Pratik Bankhele
    Creighton University, Omaha, NE
  • Jamal Jamil
    Creighton University, Omaha, NE
  • Ya Fatou Njie-Mbye
    Texas Southern University, Houston, NE
  • Madhura Kulkarni
    Texas Southern University, Houston, NE
  • Sunny Ohia
    Texas Southern University, Houston, NE
  • Catherine Opere
    Creighton University, Omaha, NE
  • Footnotes
    Commercial Relationships Ankita Salvi, None; Pratik Bankhele, None; Jamal Jamil, None; Ya Fatou Njie-Mbye, None; Madhura Kulkarni, None; Sunny Ohia, None; Catherine Opere, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1976. doi:
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      Ankita Salvi, Pratik Bankhele, Jamal Jamil, Ya Fatou Njie-Mbye, Madhura Kulkarni, Sunny Ohia, Catherine Opere; Regulation of Mammalian Sympathetic Neurotransmitter Release and Intraocular Pressure by Hydrogen Sulfide Donor, GYY 4137. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1976.

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

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Purpose: We have evidence that hydrogen sulfide (H2S) donors can regulate sympathetic neurotransmission and intraocular pressure (IOP) in the mammalian anterior uvea. In the present study, we investigated the effect of a slow releasing H2S donor, GYY 4137 on electrically evoked [3H]NE release in isolated superfused, bovine iris-ciliary bodies (ICB), in vitro and on IOP in male New Zealand White rabbits, in vivo.

Methods: Isolated bovine ICB were incubated in oxygenated Krebs solution containing 2.5 μCi/ml of [3H]NE and then prepared for neurotransmitter release studies. Release of [3H]NE was elicited by two (S1 and S2) electrical pulses (300 d.c electrical pulses) applied 27 min apart. For IOP studies, a single drop of GYY 4137 (0.1-2%) and vehicle were instilled into the right and left rabbit eyes, respectively. IOP measurements were made using a pneumatonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY) until baseline readings resumed.

Results: GYY 4137 (1-30μΜ) attenuated field-stimulated [3H]NE release in bovine ICB in a concentration-dependent manner, achieving an inhibition of 20.8% (n=3; p<0.05) at 30 µM. Although cystathionine β-synthase inhibitor, aminooxyacetic acid (3 mM) and the ATP-sensitive potassium channel (KATP) inhibitor, glibenclamide (300 µM) had no effect (p>0.05) on [3H]NE release, they both reversed the inhibitory action of GYY 4137 (10-30 µM) on the neurotransmitter release. GYY 4137 (0.1-2%) reduced IOP in both treated and untreated eyes for a duration of 7-9 h, exhibiting a maximum effect after 5-6 h. For instance, GYY 4137 (2%) elicited a maximum IOP inhibition of 27.76 % (n=5; p<0.001) 6 h after treatment in normotensive rabbits.

Conclusions: The H2S-donor, GYY 4137 attenuates both sympathetic neurotransmitter release and IOP in mammalian anterior uvea. The inhibitory action on neurotransmission is partially dependent on in situ release of H2S and on the activation of KATP-channels.

Keywords: 568 intraocular pressure • 616 neurotransmitters/neurotransmitter systems • 571 iris  

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