March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Disrupted Circuitry In The Outer Retina Following Genetic Removal Of Horizontal Cells
Author Affiliations & Notes
  • Patrick W. Keeley
    Neuroscience Research Institute,
    Molecular, Cellular, and Developmental Biology,
    University of California, Santa Barbara, California
  • Kimberly A. Skyles
    Neuroscience Research Institute,
    University of California, Santa Barbara, California
  • Mary A. Raven
    Neuroscience Research Institute,
    Molecular, Cellular, and Developmental Biology,
    University of California, Santa Barbara, California
  • Ross A. Poche
    Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas
  • Benjamin E. Reese
    Neuroscience Research Institute,
    Psychological and Brain Sciences,
    University of California, Santa Barbara, California
  • Footnotes
    Commercial Relationships  Patrick W. Keeley, None; Kimberly A. Skyles, None; Mary A. Raven, None; Ross A. Poche, None; Benjamin E. Reese, None
  • Footnotes
    Support  NIH Grant EY019968
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3955. doi:
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      Patrick W. Keeley, Kimberly A. Skyles, Mary A. Raven, Ross A. Poche, Benjamin E. Reese; Disrupted Circuitry In The Outer Retina Following Genetic Removal Of Horizontal Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3955.

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

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Abstract

Purpose: : To determine the role of horizontal cells upon the development of outer retinal circuitry, we have analyzed the Lim1 conditional knockout (CKO) mouse retina. Lim1 is expressed specifically in horizontal cells, and those lacking Lim1 fail to migrate to their correct stratum or to differentiate processes in the outer retina, becoming ectopically positioned in the inner retina. The effect of this partial depletion of horizontal cells upon the organization of the outer plexiform layer (OPL) was examined.

Methods: : Floxed Lim1 mice were crossed with Rx-Cre mice to create Lim1 retina-specific CKO mice. Immunofluorescence and confocal microscopy were used to examine the OPL in mature and developing mice, with antibodies to synaptic markers, neurofilaments, calbindin, and cone arrestin as well as fluorescently tagged PNA. Lim1 CKO mice were also crossed with Gustducin-GFP mice in order to assess the dendritic morphology of single bipolar cells labeled with DiI.

Results: : Lim1 CKO retinas showed a conspicuous decrease in the density of horizontal cell processes and a corresponding collapse of the OPL. Despite a conserved thickness of the outer nuclear layer (ONL), the OPL showed a large reduction in the density of synaptic ribbons. This decrease coincided with sprouting by rod bipolar cell dendrites into the ONL, where ectopic ribbon markers were frequently detected. Cone pedicles displayed proper stratification in the OPL and contained synaptic ribbons, but were less regularly distributed; additionally, the area of their active zones was on average smaller, though more variable. Type 7 cone bipolar cells correctly targeted these pedicles but formed smaller dendritic arbors with fewer terminal endings. Developmental analysis confirmed that horizontal cells are never present in the OPL of the CKO retina; rod spherules and rod bipolar dendrites, however, were properly stratified early in postnatal development, and a normal complement of ribbon synapses was detected. Cone pedicle distribution within the OPL appeared disrupted as early as postnatal day 9.

Conclusions: : Horizontal cells are not required for the initial targeting and synaptogenesis of the remaining OPL components; they are critical, however, for the maintenance of normal photoreceptor-bipolar cell connectivity, although different aspects of each circuit are disrupted in their absence.

Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • development • differentiation 
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