May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
A Novel Cross-Species Antagonist to A3 Adenosine Receptors Lowers Mouse Intraocular Pressure Measured Non-Invasively
Author Affiliations & Notes
  • Z. Wang
    Univ of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Physiology,
  • C. W. Do
    Univ of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Physiology,
    School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China
  • M. Y. Avila
    Dept. of Physiological Sciences, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia
  • K. Peterson
    Univ of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Physiology,
  • R. A. Stone
    Univ of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Ophthalmology,
  • Z. G. Gao
    NIDDK, National Institutes of Health, Bethesda, Maryland
  • L. S. Jeong
    College of Pharmacy, Ewha Womans University, Seoul,, Republic of Korea
  • K. A. Jacobson
    NIDDK, National Institutes of Health, Bethesda, Maryland
  • M. M. Civan
    Univ of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Physiology,
    Medicine,
  • Footnotes
    Commercial Relationships  Z. Wang, University of Pennsylvania, P; C.W. Do, University of Pennsylvania, P; M.Y. Avila, University of Pennsylvania, P; K. Peterson, None; R.A. Stone, University of Pennsylvania, P; Z.G. Gao, University of Pennsylvania, P; L.S. Jeong, University of Pennsylvania, P; K.A. Jacobson, University of Pennsylvania, P; M.M. Civan, University of Pennsylvania, P.
  • Footnotes
    Support  IH Research Grant EY13624 (MMC) and Core Grant EY01583, Paul & Evanina Bell Mackall Fdn Trust & Research to Prevent Blindness (RAS), and the Intramural Res. Prog. of NIDDK (KAJ).
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 356. doi:https://doi.org/
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      Z. Wang, C. W. Do, M. Y. Avila, K. Peterson, R. A. Stone, Z. G. Gao, L. S. Jeong, K. A. Jacobson, M. M. Civan; A Novel Cross-Species Antagonist to A3 Adenosine Receptors Lowers Mouse Intraocular Pressure Measured Non-Invasively. Invest. Ophthalmol. Vis. Sci. 2008;49(13):356. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine whether novel selective, putative cross-species antagonists of A3 adenosine receptors (ARs) lower intraocular pressure (IOP) in the living mouse. The 5 antagonists tested are modifications of Cl-IB-MECA, an effective A3-selective agonist across species.

Methods: : IOP was measured with a micropipette by the invasive Servo-Null Micropipette System (SNMS) and by non-invasive pneumotonometry before, during and after topical drug application. Bovine nonpigmented ciliary epithelial (NPE) cell volume was measured by calcein fluorescence.

Results: : The 5 agonist-based, A3AR antagonists separately lowered mouse SNMS-measured IOP by 3-5 mmHg rapidly, within several minutes of application. No effect was detected pneumotonometrically with 4 of the compounds over 30 min of observation, consistent with the slower, smaller responses previously observed following topical application of A3AR agonists and the A3AR antagonist MRS1191. LJ1251 uniquely lowered IOP measured both by pneumotonometry (by 4.2 ±0.7 mmHg after 30 min, N=6, P<0.002) and by SNMS (by 4.9 ±1.7 mmHg, N=6, P<0.05). LJ1251 (150 nM) blocked the shrinkage of native bovine NPE cells (N=8) triggered by 0.3 mM adenosine alone (N=14) (P<0.05, ANOVA).

Conclusions: : With enhanced intraocular delivery by measuring IOP invasively, 5 derivatives of the A3AR agonist Cl-IB-MECA lowered IOP. Measured non-invasively, only LJ1251 rapidly reduced IOP after topical application, and acted across species as a bovine A3AR receptor antagonist. We conclude that LJ1251 is a particularly promising A3AR antagonist for further study because of its apparent more ready permeation of the mouse ocular coats.

Keywords: adenosine • intraocular pressure 
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