Abstract
Abstract: :
Purpose: This study aims to establish behavioural differences between visually impaired RPE65-/-mice and normal sighted C57 controls. RPE65 is a gene that codes for an essential step in the visual cycle, isomerizing all-trans-retinyl esters back to 11-cis-retinol. Methods: RPE65-/- mice have been engineered to represent a visual system defective in this gene. Behavioural studies were employed to demonstrate motor differences between the groups. The mice were housed in cages that accommodate infrared photocell beams, which facilitate continuous monitoring of motor activity. Light cycles were varied over the time such that light is the driving force to assess the presence of vision. Movements were recorded continuously over a period of weeks. Data was analysed in terms of periodicity, amplitudes and acrophases, determined by spectral analysis and nonlinear regression of Halberg's cosinor analysis. Results: Data suggests clear differences between the behaviour of C57, and RPE65-/- mice. When compared to normal sighted C57 controls, RPE65-/- mice demonstrate substantially reduced activity (mean and amplitude). The RPE65-/- mice also have a reduced tendency to demonstrate a 24-hour circadian rhythm driven by the light. The ability of the C57 mice to shift their time of maximal activity 12 hours following a light shift in a short period of time is not seen in the RPE65-/- mice. Conclusion: These results suggest an almost complete functional loss in the RPE65-/- mice compared with the C57. The reliability of this approach suggests it's future role as a means of assessing recovery of visual function in ongoing ocular gene therapy work.
Keywords: 567 retinal pigment epithelium • 316 animal model • 606 transgenics/knock-outs