Visual Behaviour and Electrophysiological Function in Aged Animals Lacking the Complement Factor–H Gene

Abstract

Purpose: : To assess the visual function of aged animals lacking the complement factor–H gene.

Methods: : Visual acuity and contrast sensitivity were assessed in 2 year old transgenic mice containing a null mutation of the complement factor–H gene (CFH), and in age–matched and young controls. Acuity and contrast sensitivity were assessed using a visual water maze task. Briefly, animals were taught to discriminate between a neutral stimulus and a grating displayed pseudo–randomly on separate computer screens at the end of a water tank. Animals were trained to swim toward the screens, and, at a fixed distance, choose the screen displaying the grating that signified a submerged platform hidden below the waterline. To assess visual acuity, grating frequency was increased until performance fell below criteria. For contrast sensitivity only one grating was used. Again the contrast was reduced until performance fell below criteria indicating the animals’ visual capacity. Following completion of behavioural experiments, mice were dark–adapted overnight and anaesthetised. Electroretinography (ERG) was used to assess neural retinal function in response to flash stimuli presented via an LED stimulator (Log intensity –5 to +1) under scotopic conditions. Following 20min adaptation to a 20Cd/m² background, photopic responses to flash stimuli and flicker stimuli (up to 40Hz) were assessed.

Results: : All animals rapidly learnt a simple light–dark discrimination. This confirmed that the factor–H knockout (KO) animals were not cognitively impaired. Following initial training, visual acuity was assessed. There was a reduction in visual acuity as a result of aging between the young (0.44c/d) and old control groups (0.31c/d; approximately 27%). However, there was a further significant reduction in visual acuity between age–matched controls and 2 year old CFH KO animals (0.29c/d; approximately 9%). No significant differences were observed between any of the groups for contrast sensitivity. ERG analysis revealed a reduction in scotopic a–wave and b–wave amplitudes in CFH KO mice compared to controls at greater flash intensities (Log unit –1 +), whereas photopic responses to flashes and flicker stimuli showed little difference.

Conclusions: : In aged animals lacking the complement factor–H gene visual acuity and ERGs were significantly impaired as compared to age–matched controls.

Keywords: age-related macular degeneration • transgenics/knock-outs • degenerations/dystrophies