Date of Award
Master of Science
Dr. Kathleen Hill
Retinal degeneration, despite devastating effects, lacks therapy. Memantine has potential for preserving vision by reducing excitotoxicity associated with reactive oxygen species (ROS). A model for memantine delivery is the oxidative stress- and retinal degeneration in harlequin (hq) mice. Wild type (WT) and hq mice received untreated or memantine-treated (30 mg/kg/ day) drinking water at 1 out to 2,4,6, 8 and 10 months (mo) of age (5 males per cohort). Retinal integrity was assessed using electroretinography and ocular coherence tomography with ROS levels and apoptosis examined postmortem. Reduced hq vision was evident at 2 mo with a slight elevation in ROS at 2 mo, central retinal photoreceptor layer thinning at 4 mo and significant apoptosis at 4 mo. Excitotoxicity was not evident. Memantine had expected effects in WT mice but did not preserve hq vision. Ocular phenotyping of hq mice revealed dry age-related macular degeneration and a valid framework for testing appropriate drugs.
MacPherson, Thomas C., "Ocular Phenotyping in the harlequin Mouse Model of Retinal Degeneration: A Framework for Therapeutic Testing" (2009). Digitized Theses. 3842.