April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Cellular Changes In The Outer Retina Of DBA/2J Mice With Aging
Author Affiliations & Notes
  • Laura Fernandez-Sanchez
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Iona Raymond
    Neurobiology, University of California, Los Angeles, Los Angeles, California
  • Nicholas Brecha
    Neurobiology, University of California, Los Angeles, Los Angeles, California
    Veterans Administration, VAGLAHS, Los Angeles, California
  • Nicolas Cuenca
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Footnotes
    Commercial Relationships  Laura Fernandez-Sanchez, None; Iona Raymond, None; Nicholas Brecha, None; Nicolas Cuenca, None
  • Footnotes
    Support  MICINN (BFU2009-07793/BFI), (RETICS RD07/0062/0012), ONCE, FUNDALUCE, Fundacion Medica Mutua Madrileña to NC. VA Career Scientist and NIH EY 04067 to NB.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 706. doi:
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    • Get Citation

      Laura Fernandez-Sanchez, Iona Raymond, Nicholas Brecha, Nicolas Cuenca; Cellular Changes In The Outer Retina Of DBA/2J Mice With Aging. Invest. Ophthalmol. Vis. Sci. 2011;52(14):706.

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

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Purpose: : The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell degeneration. This mouse strain spontaneously develops essential iris atrophy, pigment dispersion, and glaucomatous changes including an increase in intraocular pressure (IOP) beginning about 4 to 6 months of age. Other changes include ganglion cell death in sectors of the retina and optic nerve atrophy. The aim of this study was to evaluate possible structural changes in the outer retina of DBA/2J mice.

Methods: : DBA/2J mice were studied at 3, 8 and 16 months, and C57BL/6 mice were used as age matched controls. Eyes were enucleated and fixed in paraformaldehyde and cryoprotected with sucrose. Retinal cryostat sections were singly or doubly immunostained for specific markers of different retinal cells.

Results: : At 3 months, the number of photoreceptor rows in the ONL of DBA/2J and C57BL/6 mice did not differ. However, synaptophysin, calbindin, GNB3 and PKC immunostaining showed that horizontal and ON- bipolar cells had shorter and less dendritic process in the OPL than the control C57BL/6 lines. At 8 months a reduction of the number of photoreceptor cell bodies was detected; ~9 rows of photoreceptor cell bodies compared with 12 -14 rows of photoreceptor cell bodies in age matched control retinas. Outgrowth of bipolar and horizontal cell processes was observed at this age as well as a reduction in the thickness of the OPL. A decrease of synaptophysin and bassoon immunoreactivity indicated a loss of synaptic connectivity between photoreceptors and postsynaptic cells. At 16 month of age, the number of photoreceptor rows was reduced to 6-8 rows and the OPL and INL were thinner compared to control retinas. There was a reduction in number of horizontal and rod bipolar cells. Ganglion cells in the DBA/2J line degenerate in patches. These patches are associated with greater retinal degeneration, beginning at 8 months with loss of ganglion cells, altered cone morphology and outgrowth of horizontal and bipolar cell processes. In the patches at 16 month old retinas, the dendritic plexus of horizontal cells are absent and there are only a few photoreceptors.

Conclusions: : In DBA/2J line, ganglion cell degeneration is accompanied by photoreceptor death and loss of synaptic contacts with horizontal and bipolar cells. This pattern of degeneration is especially prominent in patches of the retina lacking ganglion cells.

Keywords: retinal degenerations: cell biology • retina: distal (photoreceptors, horizontal cells, bipolar cells) • aging 

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