Structure/Function Studies and the Effects of Memantine in Monkeys with Experimental Glaucoma

Abstract

Purpose. The scanning laser polarimetry with variable corneal compensation (GDx VCC) methodology was established and verified in monkeys with experimental glaucoma (ExpG). Terminal GDx parameters were correlated with axon counts and electrophysiologic measures. The effects of memantine on these parameters were investigated. Methods. ExpG was induced in monkeys and intraocular pressure monitored weekly. Some monkeys received memantine in their diet before and after ExpG induction (1-10 months). GDx VCC scans, stereophotographs, and multifocal visual evoked potential (mfVEP) data were collected at baseline and every 6 to 8 weeks until euthanasia. Optic nerves were prepared for axon counting and other morphologic analysis. Results. There was no difference in IOP elevation exposure between memantine-treated and no-memantine-treated monkeys. The percentage of the optic nerve area composed of connective tissue septa was significantly greater in ExpG eyes than in Fellow eyes. There was a strong positive correlation between axon counts and terminal GDx parameter measures. Animals not receiving memantine exhibited significantly lower mfVEP amplitudes in ExpG eyes compared with the ipsilateral baseline or the final value in the Fellow eye. ExpG eyes from memantine-treated animals had higher overall mean amplitudes that were not significantly different relative to the ipsilateral baseline and final amplitudes in the Fellow eye. Conclusions. The authors' studies confirm that GDx VCC can be utilized in monkey ExpG studies to detect early retinal structural changes and that these changes are highly correlated with optic nerve axon counts. These structural changes may or may not lead to central functional changes as shown by the mfVEP in response to investigational therapies.

Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma

“…To date, the majority of the preclinical studies examining memantine for the treatment of glaucoma, intraperitoneal, subcutaneous, or oral administration routes were investigated. For studies involving oral administration in monkeys, doses of between 2 and 8 mg kg −1 day are reported, while Alzheimer's disease patients are currently prescribed between 10 and 20 mg d −1 . The local administration of memantine permitted by our nanoparticle formulation resulted in localized dosing of ≈0.125 mg/rat/day.…”

“…In Vitro Drug Release : In vitro release of memantine from MEM‐NPs was evaluated using the dialysis bag technique under sink conditions and results compared to free memantine . The release medium was composed of a PBS buffer solution (phosphate‐buffered saline (PBS) 0.1 M, pH 7.4) and temperature maintained at 32 °C (ocular surface temperature) with stirring.…”

Effect of Nmda-Receptor Blockers on the Dynamics of Intraocular Pressure in Rabbits

“…Нині серед блока-торів НМДА-рецепторів відомі препарати, для яких експериментально доведено наявність нейроретинопротекторної активності в умовах ішемії ока на тлі підвищеного ВОТ. Мова йде перш за все про похідні адамантану: меман-тин, амантадину гідрохлорид або сульфат [10,11]. Однак дані стосовно їхнього впливу на ВОТ є обмеженими та суперечливими.…”

“…Подібне явище описане при дії амантадину. У наукових публікаціях добре висвітлено його нейро-та ретинопротекторні властивості [10,28], однак наявність М-холіноблокувальних ефектів, обмежила перспективу його вико-ристання у хворих з підвищеним офталь-мотонусом, що і знайшло своє віддзерка-лення в інструкції до застосування. При вивченні впливу адемолу за різних способів введення (очні краплі та внутрішньовенна інфузія) нами встановлено наявність у нього офтольмогіпотензивного ефекту, що проявилося вірогідним зниженням ВОТ як у кролів із нормальним (не підвищеним) тиском, так і на моделі гострої тимчасової офтальмогіпертензії.…”

Strategies for Neuroprotection in Glaucoma

“…Latest animal studies have shown that using memantine in monkeys will result in an overall higher mean multifocal visual evoked potential (VEP) amplitudes than the non treated memantine monkeys when experimental glaucoma has been induced [28]. However it was not significant from baseline in the former.…”