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Novel free radical scavengers protect retinal cells and decrease elevated intraocular pressure in a rat ocular hypertension model
Author(s) -
Hosseini Alireza,
Lattanzio Frank A.,
Schellenberg Karl A.,
Samudre Sandeep S,
Shaeffer James,
Williams Patricia B.
Publication year - 2008
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.22.1_supplement.1137.9
Subject(s) - glaucoma , ocular hypertension , intraocular pressure , retinal , medicine , pharmacology , in vivo , toxicity , chemistry , ophthalmology , amifostine , microbiology and biotechnology , biology
Glaucoma is a neurodegenerative disease with damage retinal cells (RC) often associated with elevated intraocular pressure (IOP). Novel free radical scavengers (FRS) with esterified ion chelator and reducing side groups on a methoxypolyethylene glycol backbone (MPs) were evaluated as anti–glaucoma agents capable of both IOP reduction and RC protection. The operated eye of surgical rat glaucoma model received topical MPs or amifostine, a clinical FRS (all agents 20 ml, 0.3 – 100 mM). IOP was measured via Goldmann tonometer. Slit lamp, confocal microscopy and chronic toxicity 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 (2μL, 10–40mM) to naïve rats induces RC ERG and histological losses in 2 weeks. This damage was challenged with co–administered intravitreal MPs (n=5–6). Topical MPs (3–100 mM), but not amifostine, decreased IOP up to 29.6 % for T1/2s of 1–2 hrs. MPs also caused no acute or chronic ocular/systemic toxicity. 14C topical MPs showed ocular penetration with elimination via urine. MPs also reduced NMDA induced RC loss and A and B waves decreases. In vitro isolated rat and bovine RC assays are currently evaluating the role of free radical generation, elevated intracellular calcium and mitochondrial depolarization in the MPs mechanism of action in vivo. Supported in part by CHRB and AHAF.