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P. L. Kaufman, B. T. Gabelt, C. A. Rasmussen, M. S. Filla, D. M. Peters, C. R. Brandt, E. Lee; Effect of PGF Synthase Transgene Expression on Intraocular Pressure in Monkey Eyes in vivo. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2004.
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© ARVO (1962-2015); The Authors (2016-present)
To elevate PGF2a levels by lentivirus-delivered bovine lung prostaglandin F synthase (BOVPGF) gene expression and determine its effect on intraocular pressure (IOP) in monkey eyes.
Feline lentiviral (FIV) vectors expressing both BOVPGF and green fluorescent protein (GFP) (FIV.PGF.GFP) or GFP alone (FIV.GFP) were constructed. The anterior chambers of 5 cynomolgus monkeys were injected with 2.0x10e7 TU of FIV.PGF.GFP to one eye, FIV.GFP to the opposite eye. IOP was monitored by Goldmann applanation tonometry. GFP expression in vivo was visualized with a custom GFP microscope and tele-otoscope systems. Changes in PGF2α levels in the aqueous humor were determined by ELISA. Aqueous humor formation (AHF) was measured fluorophotometrically; outflow facility (OF) was measured by two-level constant pressure perfusion.
In all 5 monkeys, GFP expression was detected mainly in the trabecular meshwork area beginning 2 weeks after viral injection and was still detectable 1 year later. Inflammation in the anterior chamber subsided 1 to 2 weeks after the injections. In 3/5 eyes injected with FIV.PGF.GFP, there was a slight reduction in IOP of 2-4 mmHg compared to the contralateral FIV.GFP injected eyes detectable from 2 weeks up to 5 months post injection. These 3 monkeys also received a second injection which did not produce any additional response or restore the response if it had subsided. PGF2a levels in the aqueous humor were significantly higher (6.21±0.17pg/ml vs 4.27±0.23 pg/ml, p<0.05) in FIV.PGF.GFP injected eyes compared to FIV.GFP controls in the 3 putative responder monkeys at 44 days but not at later time points. AHF in these 3 monkeys was not measured until after the IOP response had subsided at which time (96-291 days post injection) there was no difference in between eyes in this parameter. OF measured twice during the interval 249-585 days, was significantly less in FIV.PGF.GFP compared to FIV.GFP injected eyes for n=3 or 5 (0.33±0.10 vs 0.59±0.09 µl/min/mmHg, n=3, difference, p<0.01). Tissue will be examined for PGFsynthase expression.
PGFsynthase overexpression may result in transient IOP reduction in monkeys. Changes in the expression of other pathways that may counteract the effect of PGFsynthase overexpression need to be examined.
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