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W.W. Dawson, E.C. Ogle, J. Dawson, M.A. McLaughlin; Response of Naturally Hypertensive Monkey Eyes to Common Treatments . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1546.
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To evaluate a select colony of Rhesus monkeys for response to bench–mark IOP–lowering compounds and for mechanism of ocular hypertension. Monkeys were selected from a Florida colony based on three phenotypes (Dawson et al BJO, 1993): 1) binocularly elevated IOP for more than six months (>18mmHg) with large digital cup/disc values (>0.4) (HT), 2) large digital cup/disc values (>0.4) with normal IOP (<15mmHg) for more than six months (HC/D), (3) normal cup/disc values (<0.4) with normal IOP for more than six months (Control).
Intraocular pressure (IOP) measurements were taken with the TonoPen XL (Mentor) on both eyes of ketamine–sedated animals. After baseline IOP, compound or vehicle was instilled topical ocular to one eye of each animal. Post–dose measurements were taken at 1.5, 3.0, and 4.5 hours. Facility C(tot) was then measured by tonography with the Shiotz tonometer. Studies were completed on four masked test items for both IOP and C(tot) in 24 animals (8 males in each phenotype).
Baseline IOP values for the three groups were generally 13–15 mmHg for the HC/D and Control groups and 17–19 mmHg for the OHT group. In 4.5 hours pilocarpine produced an IOP decline in 7 of 8 HT eyes (p=0.002). In HC/D eyes and Control eyes changes were insignificant. Brinzolamide produced an IOP decline in 5 of 8 HT eyes (p=0.17), 4 of 8 HC/D eyes (p=0.41) and 6 of 8 Control eyes (p=0.024). HMN–1152 lowered IOP in 6 or 8 HT eyes (p=0.003), 7 of 8 HC/D eyes (p=0.0005), 6 of 7 Control eyes (p=0.0004). C(tot) increased (p=0.022) in 7 of 7 HT eyes with pilocarpine. In 7 of 7 HC/D eyes C(tot) strongly increased (p=0.0023). In 5 of 6 control eyes C(tot) increased (p=0.025). C(tot) increased more in HC/D than HT eyes (p=0.0052). After 4.5 hours brinzolamide treatment produced no changes in C(tot). HMN–1152 increased C(tot) in HT (p=0.08) and H/CD (p=0.08) groups, but was not statistically significant.
Drug response of the three groups was as expected for pilocarpine and HMN–1152; however, the lack of results with brinzolamide was not. The mechanism by which the glaucoma–like damage is induced remains to be determined.
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