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Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma.
J Neurosci. 2013 Oct 30; 33(44):17444-57.JN

Abstract

Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using a microbead injection technique to chronically raise IOP for 15 or 30 d in mice, we identified the early changes in visual response properties of different types of retinal ganglion cells (RGCs) and correlated these changes with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well as cell death. In such eyes, multielectrode array recordings revealed that four RGC types show diverse alterations in their light responses upon IOP elevation. OFF-transient RGCs exhibited a more rapid decline in both structural and functional organizations compared with other RGCs. In contrast, although the light-evoked responses of OFF-sustained RGCs were perturbed, the dendritic arbor of this cell type remained intact. ON-transient and ON-sustained RGCs had normal functional receptive field sizes but their spontaneous and light-evoked firing rates were reduced. ON- and OFF-sustained RGCs lost excitatory synapses across an otherwise structurally normal dendritic arbor. Together, our observations indicate that there are changes in spontaneous activity and light-evoked responses in RGCs before detectable dendritic loss. However, when dendrites retract, we found corresponding changes in receptive field center size. Importantly, the effects of IOP elevation are not uniformly manifested in the structure and function of diverse RGC populations, nor are distinct RGC types perturbed within the same time-frame by such a challenge.

Authors+Show Affiliations

Department of Biological Structure, University of Washington, Seattle, Washington 98195, and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24174678

Citation

Della Santina, Luca, et al. "Differential Progression of Structural and Functional Alterations in Distinct Retinal Ganglion Cell Types in a Mouse Model of Glaucoma." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 33, no. 44, 2013, pp. 17444-57.
Della Santina L, Inman DM, Lupien CB, et al. Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma. J Neurosci. 2013;33(44):17444-57.
Della Santina, L., Inman, D. M., Lupien, C. B., Horner, P. J., & Wong, R. O. (2013). Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 33(44), 17444-57. https://doi.org/10.1523/JNEUROSCI.5461-12.2013
Della Santina L, et al. Differential Progression of Structural and Functional Alterations in Distinct Retinal Ganglion Cell Types in a Mouse Model of Glaucoma. J Neurosci. 2013 Oct 30;33(44):17444-57. PubMed PMID: 24174678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma. AU - Della Santina,Luca, AU - Inman,Denise M, AU - Lupien,Caroline B, AU - Horner,Philip J, AU - Wong,Rachel O L, PY - 2013/11/1/entrez PY - 2013/11/1/pubmed PY - 2013/12/24/medline SP - 17444 EP - 57 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 33 IS - 44 N2 - Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using a microbead injection technique to chronically raise IOP for 15 or 30 d in mice, we identified the early changes in visual response properties of different types of retinal ganglion cells (RGCs) and correlated these changes with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well as cell death. In such eyes, multielectrode array recordings revealed that four RGC types show diverse alterations in their light responses upon IOP elevation. OFF-transient RGCs exhibited a more rapid decline in both structural and functional organizations compared with other RGCs. In contrast, although the light-evoked responses of OFF-sustained RGCs were perturbed, the dendritic arbor of this cell type remained intact. ON-transient and ON-sustained RGCs had normal functional receptive field sizes but their spontaneous and light-evoked firing rates were reduced. ON- and OFF-sustained RGCs lost excitatory synapses across an otherwise structurally normal dendritic arbor. Together, our observations indicate that there are changes in spontaneous activity and light-evoked responses in RGCs before detectable dendritic loss. However, when dendrites retract, we found corresponding changes in receptive field center size. Importantly, the effects of IOP elevation are not uniformly manifested in the structure and function of diverse RGC populations, nor are distinct RGC types perturbed within the same time-frame by such a challenge. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/24174678/Differential_progression_of_structural_and_functional_alterations_in_distinct_retinal_ganglion_cell_types_in_a_mouse_model_of_glaucoma_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=24174678 DB - PRIME DP - Unbound Medicine ER -