May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
OFF Pathway Ganglion Cell Responses Are Preferentially Preserved at an Intermediate Stage of Retinal Degeneration in rd1 Mice
Author Affiliations & Notes
  • S.F. Stasheff
    Neurology, Children's Hospital – Boston, Boston, MA
  • Footnotes
    Commercial Relationships  S.F. Stasheff, None.
  • Footnotes
    Support  NSF Grant IIS–0515134
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5771. doi:
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      S.F. Stasheff; OFF Pathway Ganglion Cell Responses Are Preferentially Preserved at an Intermediate Stage of Retinal Degeneration in rd1 Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5771.

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

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Introduction: : I demonstrate relative preservation of OFF–pathway signals and more severe loss of ON–pathway signals in light–evoked responses of surviving retinal ganglion cells at an intermediate stage of retinal degeneration in the rd1 mouse, a genetic model of retinitis pigmentosa. This further quantifies changes I previously reported.

Purpose: : To distinguish differential effects of photoreceptor degeneration on ON– and OFF–pathway contributions to light–evoked responses of surviving retinal ganglion cells at a stage of partial photoreceptor loss in the rd1 mouse.

Methods: : Extracellular action potentials were recorded simultaneously from 30–90 retinal ganglion cells in the in vitro retina of wild type (wt) or rd1 mice, using a multielectrode array. A series of full field light flashes of 5–17 graded intensities was presented in pseudorandomized order. The total number of spikes in each response was averaged over ten repetitions of this series, and broad groups of ganglion cells were recognized according to the relative proportion of response to light onset or offset, and to response latency and duration.

Results: : In both rd1 and wt mice at postnatal day 14–15 (P14–15), most ganglion cells (wt: 84.3%, rd1: 87.1%) have mixed ON and OFF responses. Across the population, the magnitude of the ON component was more severely reduced than that of the OFF component in rd1 cells. Correspondingly, the relative proportion of all ganglion cells that was ON–dominated (17%) was less than in wt (31%), while that of OFF–dominated cells (56% in rd1 vs. 46% in wt) or those without ON–OFF dominance was greater (27% in rd1 vs. 23% in wt). On brisk transient cells were conspicuously rare in the rd1 population.

Conclusions: : Photoreceptor degeneration in rd1 mice has a differential effect on two parallel inner retinal pathways: OFF responses are relatively preserved, while ON responses have deteriorated more severely at this stage of degeneration. Though the mechanism of this differential effect remains to be determined, it is possible that compensatory changes selective to the OFF pathway are related to the spontaneous hyperactivity I have recently confirmed in this model.

Keywords: retinal degenerations: hereditary • ganglion cells • electrophysiology: non-clinical 

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