Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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).
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).
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.
This PDF is available to Subscribers Only