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Effects of Novel Free Radical Scavengers on Intraocular Pressure and Electroretinograms in Rat Glaucoma Models
Author(s) -
Hosseini Alireza,
Lattanzio Frank A,
Schellenberg Karl,
Shaeffer James,
Samudre Sandeep S,
Williams Patricia B
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a689-c
Subject(s) - intraocular pressure , ocular hypertension , medicine , glaucoma , ophthalmology , amifostine , pharmacology , toxicity
Introduction Glaucoma is often associated with elevated intraocular pressure (IOP) and damage to retinal ganglion cells (RGC). Novel free radical scavengers (FRS) with esterified ion chelator side groups on a methoxypolyethylene glycol backbone (MPs) were evaluated as anti–glaucoma agents using IOP reduction and RGC protection criteria. Methods The operated eye of surgical rat glaucoma model received topical MPs or topical amifostine, a clinical FRS standard (all agents 20 μl, 0.3 – 100 mM). IOP was measured via Goldmann tonometer. Slit lamp and confocal microscopy ocular toxicity chronic studies were performed on normal rats (10 or 87 mM MPs, 3x/day for 30 days). 14C MPs were used for pharmacokinetic studies. Intravitreal injection with NMDA induces RGC loss; rats were challenged with NMDA plus co–administered intravitreal or topical MPs or amifostine (n=5–6). Results ‐Topical MPs (3–100 mM), but not amifostine, decreased IOP up to 29.6 % for T1/2s of 1–2 hrs. ‐MPs caused no acute or chronic adverse ocular or systemic effects. ‐14C topical MPs showed ocular penetration with elimination via urine. ‐MPs and amifostine reduced NMDA‐RGC loss of A and B waves.Conclusions MPs are non‐toxic, can lower IOP for up to 3–4 hrs and protect against NMDA excitotoxicity. “Supported in part by the Commonwealth Health Research Board and The American Health Assistance Foundation”