The Electrophysiological Properties and Morphological Ultrastructure of N-nitroso-N-methylurea-induced Retinal Degeneration in Mice

Abstract

Objective: To study the electrophysiological properties and morphological ultrastructure of MNU-induced retinal degeneration in mice. Methods: In this experimental study, C57/BL mice were randomly divided into two groups: a control group and a MNU group. Patch-clamp recording was used to observe the responses of bipolar cells to several drugs. The ultrastructure of the retina was observed with a transmission electron microscope. Results: The results of the patch-clamp recordings showed more serious damage to ON-bipolar cells (ON-BC) than OFF-bipolar cells (OFF-BC). Seven days after MNU application, no response was observed from the application of mGlu antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) in ON-BC of the MNU group, while a reduced current (pA) of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) induced response was observed in OFF-BC. Two days after MNU administration, a decrease in the thickness of disk membranes was observed in outer segments. Five days after MNU administration, outer segments could not be observed; swollen mitochondria were observed in the inner segment. Ten days after MNU administration, inner segments could not be observed, retinas displayed decreased thickness and concentrated nucleus coloring in the outer nuclear layer. In the retinal bipolar cell remnants, widening of the perinuclear space and autophagosome was detected by electron microscopy. Conclusions: MNU leads to more serious damage in ON-BC than OFF-BC. MNU-induced retinal degeneration is limited to the outer retina, including the photoreceptor and outer plexiform layer. The mechanism of MNU-induced damage is apoptosis. Key words: N-Nitroso-N-methylurea; retinal degeneration; ultrastructure; electron microscope; apoptosis; mice