Charng Jason, He Zheng, Vingrys Algis J, Fish Rebecca L, Gurrell Rachel, Bui Bang V, Nguyen Christine T
Department of Optometry & Vision Sciences, University of Melbourne, Parkville, VIC 3010, Australia.
Pfizer Neusentis, Cambridge CB21 6GS, UK.
J Ophthalmol. 2016;2016:5801826. doi: 10.1155/2016/5801826. Epub 2016 Apr 27.
Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.
目的。研究视网膜电生理学是否是药物进入中枢神经系统（CNS）的有用替代标志物。材料与方法。在全身或局部给予可穿透中枢的化合物（蝇蕈醇）或不可穿透的化合物（异鹅去氧胆酸）后，通过全视野视觉诱发电位和视网膜电图对清醒和麻醉大鼠的脑和视网膜电生理学进行评估。结果。眼部/脑部局部注射绕过了血神经屏障，两种药物均引起视网膜/脑反应的变化。在清醒动物中，全身给予蝇蕈醇导致视网膜和脑生物电位变化，而全身给予异鹅去氧胆酸则未引起变化。全身麻醉混淆了这些结果。结论。在清醒动物中记录时，视网膜电生理学有望成为药物穿透中枢神经系统的可行生物标志物。相比之下，在麻醉条件下进行时，皮层和视网膜电生理记录均可产生混淆。
