September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dark rearing slows deterioration of retinal ganglion cell light-evoked responses in rd10 mice and extends a period of immature retinal ganglion cell physiology
Author Affiliations & Notes
  • Steven F Stasheff
    Retinal Physiology section, National Eye Institute, Bethesda, Maryland, United States
    Center for Neurosciences & Behavioral Medicine, National Eye Institute & Children's National Health System, Bethesda, Maryland, United States
  • Malini Shankar
    Retinal Physiology section, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Steven Stasheff, None; Malini Shankar, None
  • Footnotes
    Support  March of Dimes Research Grant # 12-FY11-200
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Steven F Stasheff, Malini Shankar; Dark rearing slows deterioration of retinal ganglion cell light-evoked responses in rd10 mice and extends a period of immature retinal ganglion cell physiology. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Recent experience in clinical gene therapy trials suggests that we might substantially enhance the effectiveness of emerging treatments for retinal degenerations through concurrent intervention that delays or slows degenerative processes, or that extends a developmental period of heightened neural plasticity. We report that a simple environmental manipulation, dark rearing, substantially slows the progressive loss of retinal ganglion cell (RGC) responsiveness in a widely-studied animal model, the rd10 mouse. It also roughly doubles the duration of a developmental period during which RGCs exhibit abnormal, immature physiology.

Methods : Separate cohorts of wild-type (wt) and rd10 mice were raised from birth either in complete darkness or in a standard 12-hour light/12-hour dark cycle. Using in vitro multielectrode recording, we compared retinal ganglion cell (RGC) spontaneous and light-evoked activity (full field flashes or pseudorandom checkerboard stimuli) among these cohorts, from perinatal to adult ages.

Results : As we reported previously, spontaneous hyperactivity emerged near the age of first eye opening in rd10 mice raised with standard lighting, and an abnormally high proportion of RGCs exhibited sustained flash-evoked responses through ~postnatal day (P)18. After this age, we found a relatively normal proportion of transient and sustained responses in the RGC population, although the strength of responses declined until none were detected by ~P60. In dark-reared rd10 mice, hyperactivity developed with a similar developmental time course, but an abnormally high proportion of prolonged, sustained flash responses continued through ~P38, and thereafter responses decayed more slowly, with some detected up to ~P120. Dark rearing did not change these features in wt RGC populations.

Conclusions : Dark rearing slows the rate of decay in rd10 RGC light responses, and prolongs an atypical developmental period of abnormally sustained responses. This confirms that such a simple environmental manipulation can extend the time window during which RGCs of a degenerating retina remain responsive to light. It suggests that a window of developmental plasticity in degenerative mechanisms also is prolonged by dark rearing. This may provide a unique opportunity to improve chances for gene therapy and other treatments to rescue vision.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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