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Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse.
Invest Ophthalmol Vis Sci. 2014 Aug 12; 55(9):6059-72.IO

Abstract

PURPOSE

The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line.

METHODS

Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls.

RESULTS

The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost.

CONCLUSIONS

Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

Authors+Show Affiliations

Department of Physiology, Genetics, and Microbiology, University of Alicante, San Vicente del Raspeig, Spain.Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States.Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States.Department of Physiology, Genetics, and Microbiology, University of Alicante, San Vicente del Raspeig, Spain.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25118265

Citation

Fernández-Sánchez, Laura, et al. "Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse." Investigative Ophthalmology & Visual Science, vol. 55, no. 9, 2014, pp. 6059-72.
Fernández-Sánchez L, de Sevilla Müller LP, Brecha NC, et al. Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse. Invest Ophthalmol Vis Sci. 2014;55(9):6059-72.
Fernández-Sánchez, L., de Sevilla Müller, L. P., Brecha, N. C., & Cuenca, N. (2014). Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse. Investigative Ophthalmology & Visual Science, 55(9), 6059-72. https://doi.org/10.1167/iovs.14-14421
Fernández-Sánchez L, et al. Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse. Invest Ophthalmol Vis Sci. 2014 Aug 12;55(9):6059-72. PubMed PMID: 25118265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse. AU - Fernández-Sánchez,Laura, AU - de Sevilla Müller,Luis Pérez, AU - Brecha,Nicholas C, AU - Cuenca,Nicolás, Y1 - 2014/08/12/ PY - 2014/8/14/entrez PY - 2014/8/15/pubmed PY - 2014/11/19/medline KW - bipolar cell KW - glaucoma KW - horizontal cell KW - photoreceptor KW - retinal degeneration KW - synaptic triad SP - 6059 EP - 72 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 55 IS - 9 N2 - PURPOSE: The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. METHODS: Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. RESULTS: The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. CONCLUSIONS: Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/25118265/Loss_of_outer_retinal_neurons_and_circuitry_alterations_in_the_DBA/2J_mouse_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.14-14421 DB - PRIME DP - Unbound Medicine ER -