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Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension.
Invest Ophthalmol Vis Sci. 2015 Feb 26; 56(3):1971-84.IO

Abstract

PURPOSE

We investigated the progressive degeneration of retinal and superior collicular functions in a mouse model of sustained ocular hypertension.

METHODS

Focal laser illumination and injection of polystyrene microbeads were used to induce chronic ocular hypertension. Retinal ganglion cell (RGC) loss was characterized by in vivo optical coherence tomography (OCT) and immunohistochemistry. Retinal dysfunction was also monitored by the full-field ERG. Retinal ganglion cell light responses were recorded using a 256-channel multielectrode array (MEA), and RGC subtypes were characterized by noncentered spike-triggered covariance (STC-NC) analysis. Single-unit extracellular recordings from superficial layers of the superior colliculus (SC) were performed to examine the receptive field (RF) properties of SC neurons.

RESULTS

The elevation of intraocular pressure (IOP) lasted 4 months in mice treated with a combination of laser photocoagulation and microbead injection. Progressive RGC loss and functional degeneration were confirmed in ocular hypertensive (OHT) mice. These mice had fewer visually responsive RGCs than controls. Using the STC-NC analysis, we classified RGCs into ON, OFF, and ON-OFF functional subtypes. We showed that ON and OFF RGCs were more susceptible to the IOP elevation than ON-OFF RGCs. Furthermore, SC neurons of OHT mice had weakened responses to visual stimulation and exhibited mismatched ON and OFF subfields and irregular RF structure.

CONCLUSIONS

We demonstrated that the functional degeneration of RGCs is subtype-dependent and that the ON and OFF pathways from the retina to the SC were disrupted. Our study provides a foundation to investigate the mechanisms underlying the progressive vision loss in experimental glaucoma.

Authors+Show Affiliations

Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.

Pub Type(s)

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

Language

eng

PubMed ID

25722210

Citation

Chen, Hui, et al. "Progressive Degeneration of Retinal and Superior Collicular Functions in Mice With Sustained Ocular Hypertension." Investigative Ophthalmology & Visual Science, vol. 56, no. 3, 2015, pp. 1971-84.
Chen H, Zhao Y, Liu M, et al. Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension. Invest Ophthalmol Vis Sci. 2015;56(3):1971-84.
Chen, H., Zhao, Y., Liu, M., Feng, L., Puyang, Z., Yi, J., Liang, P., Zhang, H. F., Cang, J., Troy, J. B., & Liu, X. (2015). Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension. Investigative Ophthalmology & Visual Science, 56(3), 1971-84. https://doi.org/10.1167/iovs.14-15691
Chen H, et al. Progressive Degeneration of Retinal and Superior Collicular Functions in Mice With Sustained Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Feb 26;56(3):1971-84. PubMed PMID: 25722210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension. AU - Chen,Hui, AU - Zhao,Yan, AU - Liu,Mingna, AU - Feng,Liang, AU - Puyang,Zhen, AU - Yi,Ji, AU - Liang,Peiji, AU - Zhang,Hao F, AU - Cang,Jianhua, AU - Troy,John B, AU - Liu,Xiaorong, Y1 - 2015/02/26/ PY - 2015/2/28/entrez PY - 2015/2/28/pubmed PY - 2015/8/26/medline KW - multielectrode array KW - neural degeneration KW - ocular hypertension KW - retinal ganglion cells KW - superior colliculus SP - 1971 EP - 84 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 56 IS - 3 N2 - PURPOSE: We investigated the progressive degeneration of retinal and superior collicular functions in a mouse model of sustained ocular hypertension. METHODS: Focal laser illumination and injection of polystyrene microbeads were used to induce chronic ocular hypertension. Retinal ganglion cell (RGC) loss was characterized by in vivo optical coherence tomography (OCT) and immunohistochemistry. Retinal dysfunction was also monitored by the full-field ERG. Retinal ganglion cell light responses were recorded using a 256-channel multielectrode array (MEA), and RGC subtypes were characterized by noncentered spike-triggered covariance (STC-NC) analysis. Single-unit extracellular recordings from superficial layers of the superior colliculus (SC) were performed to examine the receptive field (RF) properties of SC neurons. RESULTS: The elevation of intraocular pressure (IOP) lasted 4 months in mice treated with a combination of laser photocoagulation and microbead injection. Progressive RGC loss and functional degeneration were confirmed in ocular hypertensive (OHT) mice. These mice had fewer visually responsive RGCs than controls. Using the STC-NC analysis, we classified RGCs into ON, OFF, and ON-OFF functional subtypes. We showed that ON and OFF RGCs were more susceptible to the IOP elevation than ON-OFF RGCs. Furthermore, SC neurons of OHT mice had weakened responses to visual stimulation and exhibited mismatched ON and OFF subfields and irregular RF structure. CONCLUSIONS: We demonstrated that the functional degeneration of RGCs is subtype-dependent and that the ON and OFF pathways from the retina to the SC were disrupted. Our study provides a foundation to investigate the mechanisms underlying the progressive vision loss in experimental glaucoma. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/25722210/Progressive_degeneration_of_retinal_and_superior_collicular_functions_in_mice_with_sustained_ocular_hypertension_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.14-15691 DB - PRIME DP - Unbound Medicine ER -