Abstract
In animal models, monocular deprivation (MD) by lid closure mimics the effects of unilateral amblyopia in humans. Temporary inactivation of one or both eyes with intraocular administration of tetrodotoxin (TTX) has recently been shown to promote recovery from the anatomical effects of MD at post-critical period ages when standard recovery strategies fail. In the current study, the retinae and optic nerves of animals subjected to 10 days of monocular retinal inactivation were assessed for pathological changes as a means of assessing the viability of this potential new amblyopia therapy. Retinal sections from both eyes were subjected to hematoxylin and eosin staining and were then examined for cell density and soma size in the ganglion cell layer (GCL). Sections of the optic nerve from each eye were examined for neurofilament protein, myelin, glial cell density, and glial fibrillary acidic protein (GFAP). Our study revealed no evidence of gross histopathological abnormalities following inactivation for 10 days, nor was there evidence of degeneration of axons or loss of myelin in the optic nerve serving inactivated eyes. On all measurements, the inactivated eye was indistinguishable from the fellow eye, and both were comparable to normal controls. We confirmed that our inactivation protocol obliterated visually-evoked potentials for 10 consecutive days, but visual responses were restored to normal after the effects of inactivation wore off. Notwithstanding the critical need for further assessment of ocular and retinal health following inactivation, these results provide evidence that retinal inactivation as a treatment for amblyopia does not produce significant retinal damage or degeneration.
Highlights
Deprivation of normal binocular vision early in postnatal life can have a profound and permanent negative consequence on the structure and function of cells in the central visual pathways (Wiesel and Hubel, 1963a,b)
Visually-evoked potentials (VEPs) were measured from the visual cortex of the fourth group of animals that contained two animals subjected to monocular deprivation (MD) at postnatal day 30 for 5 weeks, at 10 weeks of age had the right eye inactivated for 10 days with intravitreal administration of TTX
The size and distribution of cells within the ganglion cell layer (GCL) were comparable between sections from the left and right eye in normal controls, as well as in animals whose right retina was inactivated for 10 days
Summary
Deprivation of normal binocular vision early in postnatal life can have a profound and permanent negative consequence on the structure and function of cells in the central visual pathways (Wiesel and Hubel, 1963a,b). Assessment of Histopathology Following Retinal Inactivation (Wiesel and Hubel, 1963b) as well as shrinkage of axonal terminal fields within the visual cortex (Friedlander et al, 1982; Antonini and Stryker, 1993). The aggregation of these deprivation-induced neural abnormalities produces severe vision impairment in the deprived eye, amblyopia, which in humans is the most common cause of childhood visual impairment (Webber and Wood, 2005) that can persist even if normal visual input is restored (Dews and Wiesel, 1970; von Noorden et al, 1970; Giffin and Mitchell, 1978). Beyond about the third postnatal month, little to no recovery is observed when the deprivation is reversed to the stronger fellow eye (Blakemore and Van Sluyters, 1974; Dursteler et al, 1976; Movshon, 1976; Mitchell et al, 1984)
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