July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Brief Retinal Inactivation Promotes Recovery From Long-Term Monocular Deprivation
Author Affiliations & Notes
  • Kevin Duffy
    Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  • Donald E Mitchell
    Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada
  • Footnotes
    Commercial Relationships   Kevin Duffy, None; Donald Mitchell, None
  • Footnotes
    Support  NSERC Grant RGPIN-2015-05320; CIHR Grant 374449
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4121. doi:
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      Kevin Duffy, Donald E Mitchell; Brief Retinal Inactivation Promotes Recovery From Long-Term Monocular Deprivation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4121.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Monocular deprivation (MD) in early postnatal life alters the structure and function of neurons within the lateral geniculate nucleus (LGN) and primary visual cortex of cats and primates. The consequence of these deprivation-induced modifications is a large visual acuity deficit in the deprived eye that mimics many characteristics typical of human amblyopia. In the current study we examined the extent of recovery from a long period of MD following temporary pharmacological inactivation of retinal ganglion cell activity in the non-deprived eye with intraocular injection of tetrodotoxin (TTX).

Methods : We investigated the efficacy of retinal inactivation therapy in cats that were monocularly deprived by eyelid closure for durations that ranged from 6 weeks to 18 weeks initiated at the peak of the critical period. Following the period of MD, animals received intraocular injections of TTX into the non-deprived (fellow) eye so as to inactivate the retina for 10 days. From Nissl-stained sections of LGN, neuron counts were performed using the optical dissector stereological probe, and measurements of neuron cross-sectional soma size were made using the nucleator stereology probe.

Results : Following long-term MD, there was a large reduction in the cross-sectional soma area in deprived LGN laminae that ranged from 30-35%. Whereas simple reversal of the deprivation to the stronger fellow eye by eyelid closure for 10 days produced little recovery, inactivation of the stronger fellow eye for the same duration produced substantial recovery of deprived neurons so that deprived and non-deprived neurons were of equal size. As the length of MD was increased to between 14 and 18 weeks, we found that fellow-eye inactivation produced substantial but incomplete recovery suggesting that treatment efficacy may be regulated by age. Nevertheless, retinal inactivation was consistently more effective than conventional treatment at producing recovery in older animals following long durations of MD.

Conclusions : We conclude that inactivation of the non-deprived (fellow) eye with intraocular application of TTX represents an effective means of promoting recovery in older animals for which conventional treatments are ineffective. This novel therapeutic approach for recovery from deprivation-induced impairment offers the benefits of being fast-acting, and obviates the concern over compliance that can compromise outcomes from other treatments.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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