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F. A. Lattanzio, Jr., K. A. Schellenberg, S. S. Samudre, A. Hosseini, P. B. Williams; Topical Treatment With WIN55-212-2 and Free Radical Scavengers MPDTE and MPSEDE Reduced IOP and Preserved Retinal Status in Acute and Chronic Rat Ocular Models. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3170.
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© ARVO (1962-2015); The Authors (2016-present)
Recent emphasis on glaucoma treatment has revolved around the development of agents that might have neuroprotective properties. We have investigated several novel synthetic free radical scavengers that can also reduce elevated intraocular pressure (IOP) in a rat model. The current study determines if they can preserve retinal function in acute and chronic rat models.
NMDA (2ul, 100mM) was injected intravitreally into both eyes of groups of 6 SD rats that had been pretreated 4 days with topical vehicle, 100mM MPSEDE or 100 mM MPDTE (t.i.d.), followed by 2 weeks of treatment.. In another series of experiments, groups of 7 SD rats that had surgically generated ocular hypertension OD were treated OD for 6 months t.i.d. with vehicle, WIN 55-212-2, MPEDE or MPDTE. Full field ERGs (ffERGs) and histology was used to examine retinal function in both cases, together with IOP, McDonald Shadduck and slit lamp exams and clinical chemistries.
In the NMDA experiments, MPDTE or MPSEDE mitigated the NMDA induced retinal damage and were significantly effective compared to vehicle alone (p<0.003). Untreated NMDA ffERG a-b wave activity was significantly reduced to 85±16 µV from a baseline of 295±5 µV (p<0.001), with significant improvements to 160±13 µV (MPSEDE) and 154±13 µV (MPDTE) (p<0.05). In the chronic experiment, treatment with WIN, MPDTE or MPSEDE significantly suppressed (p<0.05) the IOP elevation created by the surgery. However, there was no statistically significant difference between the drug treated groups. The prolonged elevation in IOP also compromised retinal status as ffERG response in the vehicle treated ligated eyes was 47±6% of the unligated contralateral control eyes. Treatment with MPSEDE or MPDTE mitigated this decline in retinal status to 70±9% and 72±6% respectively, (p<0.0001, n=7/group). There was no decline in retinal status after treatment with WIN. Clinical chemistries remained within normal limits. There were no untoward systemic effects caused by any of the agents. The only drug related problem noted involved minor ocular irritation in some of the MPSEDE rats.
The topical, free radical scavengers MPDTE and MPSEDE and cannabinoid WIN can safely reduce IOP and protect retinal cells in both acute and chronic rat models with pathological elements that may be seen in glaucoma, without adverse systemic effects.
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