OPTIC NERVE INTERGRITY FOLLOWING RETINAL INACTIVATION FOR THE TREATMENT OF POST-CRITICAL PERIOD AMBLYOPIA

Abstract

In animal models, monocular deprivation (MD) by lid closure mimics the effects of unilateral amblyopia in humans. In cats, inactivation of the fellow (non-deprived) eye, with intraocular administration of tetrodotoxin has recently been shown to promote significant recovery from the effects of MD at older ages when conventional occlusion therapy fails. In the current study, the optic nerves of cats subjected to retinal inactivation of the fellow eye were assessed for histopathological changes as a means of assessing the safety of this potential new therapy. We examined the optic nerves of cats that were subject to up to 10 days of monocular inactivation therapy in their right eye and compared them to their left, control eye, as well as to the optic nerves from a control group of cats reared binocularly. In order to determine the extent of ocular imbalance for animals subjected to unilateral retinal inactivation therapy, the left and right optic nerves from all animals were assessed for signs of degeneration. This included observing for alterations in neurofilament labelling to assess axonal integrity, selectively staining myelin with luxol fast blue to asses for modifications of the myelin sheath, Nissl staining to quantify glial cell density, and immunolabeling for glial fibrillary acidic protein to asses for signs of gliosis. Our study revealed no evidence of gross histopathological changes in any of the markers assessed, revealing a normal balance between the left and right optic nerves from all animals and across both the treatment groups. These results indicate that retinal inactivation treatment did not significantly alter the integrity of the optic nerve and may be a viable therapeutic option for the treatment of post-critical period amblyopia.