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Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties.
J Neurosci. 2019 03 06; 39(10):1881-1891.JN

Abstract

Elevation of intraocular pressure (IOP) causes retinal ganglion cell (RGC) dysfunction and death and is a major risk factor for glaucoma. We used a bead injection technique to increase IOP in mice of both genders by an average of ∼3 mmHg for 2 weeks. This level of IOP elevation was lower than that achieved in other studies, which allowed for the study of subtle IOP effects. We used multielectrode array recordings to determine the cellular responses of RGCs exposed to this mild degree of IOP elevation. We found that RGC photopic receptive field (RF) center size and whole-field RGC firing rates were unaffected by IOP elevation. In contrast, we found that the temporal properties of RGC photopic responses in the RF center were accelerated, particularly in ON sustained cells. We also detected a loss of antagonistic surround in several RGC subtypes. Finally, spontaneous firing rate, interspike interval variance, and contrast sensitivity were altered according to the magnitude of IOP exposure and also displayed an IOP-dependent effect. Together, these results suggest that individual RGC physiologic parameters have unique IOP-related functional thresholds that exist concurrently and change following IOP elevation according to specific patterns. Furthermore, even subtle IOP elevation can impart profound changes in RGC function, which in some cases may occur in an IOP-dependent manner. This system of overlapping functional thresholds likely underlies the complex effects of elevated IOP on the retina.SIGNIFICANCE STATEMENT Retinal ganglion cells (RGCs) are the obligate output neurons of the retina and are injured by elevated intraocular pressure (IOP) in diseases such as glaucoma. In this study, a subtle elevation of IOP in mice for 2 weeks revealed distinct IOP-related functional thresholds for specific RGC physiologic parameters and sometimes showed an IOP-dependent effect. These data suggest that overlapping IOP-related thresholds and response profiles exist simultaneously in RGCs and throughout the retina. These overlapping thresholds likely explain the range of RGC responses that occur following IOP elevation and highlight the wide capacity of neurons to respond in a diseased state.

Authors+Show Affiliations

Department of Ophthalmology, and.Department of Ophthalmology, and. Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.Department of Ophthalmology, and.Department of Ophthalmology, and. Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.Department of Ophthalmology, and benjamin.frankfort@bcm.edu. Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.

Pub Type(s)

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

Language

eng

PubMed ID

30622167

Citation

Tao, Xiaofeng, et al. "Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 39, no. 10, 2019, pp. 1881-1891.
Tao X, Sabharwal J, Seilheimer RL, et al. Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties. J Neurosci. 2019;39(10):1881-1891.
Tao, X., Sabharwal, J., Seilheimer, R. L., Wu, S. M., & Frankfort, B. J. (2019). Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 39(10), 1881-1891. https://doi.org/10.1523/JNEUROSCI.2085-18.2019
Tao X, et al. Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties. J Neurosci. 2019 03 6;39(10):1881-1891. PubMed PMID: 30622167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties. AU - Tao,Xiaofeng, AU - Sabharwal,Jasdeep, AU - Seilheimer,Robert L, AU - Wu,Samuel M, AU - Frankfort,Benjamin J, Y1 - 2019/01/08/ PY - 2018/08/14/received PY - 2018/12/18/revised PY - 2019/01/03/accepted PY - 2019/1/10/pubmed PY - 2020/3/24/medline PY - 2019/1/10/entrez KW - IOP KW - RGC KW - cellular function KW - glaucoma KW - intraocular pressure KW - retinal ganglion cell SP - 1881 EP - 1891 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 39 IS - 10 N2 - Elevation of intraocular pressure (IOP) causes retinal ganglion cell (RGC) dysfunction and death and is a major risk factor for glaucoma. We used a bead injection technique to increase IOP in mice of both genders by an average of ∼3 mmHg for 2 weeks. This level of IOP elevation was lower than that achieved in other studies, which allowed for the study of subtle IOP effects. We used multielectrode array recordings to determine the cellular responses of RGCs exposed to this mild degree of IOP elevation. We found that RGC photopic receptive field (RF) center size and whole-field RGC firing rates were unaffected by IOP elevation. In contrast, we found that the temporal properties of RGC photopic responses in the RF center were accelerated, particularly in ON sustained cells. We also detected a loss of antagonistic surround in several RGC subtypes. Finally, spontaneous firing rate, interspike interval variance, and contrast sensitivity were altered according to the magnitude of IOP exposure and also displayed an IOP-dependent effect. Together, these results suggest that individual RGC physiologic parameters have unique IOP-related functional thresholds that exist concurrently and change following IOP elevation according to specific patterns. Furthermore, even subtle IOP elevation can impart profound changes in RGC function, which in some cases may occur in an IOP-dependent manner. This system of overlapping functional thresholds likely underlies the complex effects of elevated IOP on the retina.SIGNIFICANCE STATEMENT Retinal ganglion cells (RGCs) are the obligate output neurons of the retina and are injured by elevated intraocular pressure (IOP) in diseases such as glaucoma. In this study, a subtle elevation of IOP in mice for 2 weeks revealed distinct IOP-related functional thresholds for specific RGC physiologic parameters and sometimes showed an IOP-dependent effect. These data suggest that overlapping IOP-related thresholds and response profiles exist simultaneously in RGCs and throughout the retina. These overlapping thresholds likely explain the range of RGC responses that occur following IOP elevation and highlight the wide capacity of neurons to respond in a diseased state. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/30622167/Mild_Intraocular_Pressure_Elevation_in_Mice_Reveals_Distinct_Retinal_Ganglion_Cell_Functional_Thresholds_and_Pressure_Dependent_Properties_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=30622167 DB - PRIME DP - Unbound Medicine ER -