May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Ocular Hypotensive and Neuroprotective Effects of Propentofylline
Author Affiliations & Notes
  • I.-H. Pang
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • D. L. Fleenor
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • P. E. Hellberg
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • H. Zeng
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • E. C. Johnson
    Ophthalmology, Casey Eye Inst - OHSU, Portland, Oregon
  • J. C. Morrison
    Ophthalmology, Casey Eye Inst - OHSU, Portland, Oregon
  • A. F. Clark
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • Footnotes
    Commercial Relationships  I. Pang, Employee of Alcon, E; D.L. Fleenor, Employee of Alcon, E; P.E. Hellberg, Employee of Alcon, E; H. Zeng, Employee of Alcon, E; E.C. Johnson, Supported by Alcon, C; J.C. Morrison, Supported by Alcon, C; A.F. Clark, Employee of Alcon, E.
  • Footnotes
    Support  Alcon
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5509. doi:https://doi.org/
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    • Get Citation

      I.-H. Pang, D. L. Fleenor, P. E. Hellberg, H. Zeng, E. C. Johnson, J. C. Morrison, A. F. Clark; The Ocular Hypotensive and Neuroprotective Effects of Propentofylline. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5509. doi: https://doi.org/.

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

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Abstract

Purpose: : Propentofylline (PPF) has many pharmacological effects. It upregulates matrix metalloproteinases (MMPs) and neurotrophic factors, inhibits phosphodiesterase and adenosine reuptake, and protects against excitotoxicity. We determined whether PPF affects intraocular pressure (IOP) and is neuroprotective in glaucoma models.

Methods: : PPF was tested for its effects on (1) proMMP-3 level in cultured human TM cells, (2) aqueous outflow in perfusion cultured human anterior segments, (3) cell survival in rat retinal ganglion cells (RGCs), and (4) IOP and optic nerve damage in a rat glaucoma model (episcleral vein injection with hypertonic saline).

Results: : Treatment of cultured human TM cells with PPF significantly increased proMMP-3 expression by 229 ± 19% (mean ± SEM, n = 47, p < 0.001). PPF (100 µM) significantly (p < 0.05) enhanced outflow facility by 20-30% at 1-3 days in perfused human anterior segments, together with an 20-40% increase (p < 0.05) of proMMP-3 levels in the perfusate. In cultured rat RGCs, PPF (100 µM) was protective against glutamate- and trophic factor withdrawal-induced cytotoxicity (p < 0.05). The IOPs in the glaucomatous rats receiving oral PPF (30 mg/kg/d) were lower (32.5 ± 1.1 mmHg) compared to the vehicle group (35.3 ± 1.2 mmHg; n = 15; p = 0.1). Most importantly, the optic nerve damage score was significantly lower in the PPF-treated group (1.9 ± 0.4) compared to the vehicle group (2.8 ± 0.4; n = 15, p < 0.05).

Conclusions: : PPF lowered IOP and was neuroprotective in in vitro, ex vivo, and in vivo models of glaucoma. The multiple cellular actions of PPF explain these multiple beneficial effects. This compound is an interesting, novel compound that deserves further investigation of its potential in treating glaucoma.

Keywords: ganglion cells • extracellular matrix • optic nerve 
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