Tags

Type your tag names separated by a space and hit enter

Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse.
Proc Natl Acad Sci U S A. 2017 08 15; 114(33):8859-8864.PN

Abstract

Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease.

Authors+Show Affiliations

Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030; jsab1208@gmail.com. Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030. Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.

Pub Type(s)

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

Language

eng

PubMed ID

28760976

Citation

Sabharwal, J, et al. "Elevated IOP Alters the Space-time Profiles in the Center and Surround of Both ON and OFF RGCs in Mouse." Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 33, 2017, pp. 8859-8864.
Sabharwal J, Seilheimer RL, Tao X, et al. Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse. Proc Natl Acad Sci U S A. 2017;114(33):8859-8864.
Sabharwal, J., Seilheimer, R. L., Tao, X., Cowan, C. S., Frankfort, B. J., & Wu, S. M. (2017). Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse. Proceedings of the National Academy of Sciences of the United States of America, 114(33), 8859-8864. https://doi.org/10.1073/pnas.1706994114
Sabharwal J, et al. Elevated IOP Alters the Space-time Profiles in the Center and Surround of Both ON and OFF RGCs in Mouse. Proc Natl Acad Sci U S A. 2017 08 15;114(33):8859-8864. PubMed PMID: 28760976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse. AU - Sabharwal,J, AU - Seilheimer,R L, AU - Tao,X, AU - Cowan,C S, AU - Frankfort,B J, AU - Wu,S M, Y1 - 2017/07/31/ PY - 2017/8/2/pubmed PY - 2018/5/24/medline PY - 2017/8/2/entrez KW - IOP KW - glaucoma KW - multielectrode array KW - receptive field KW - retinal ganglion cell SP - 8859 EP - 8864 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 114 IS - 33 N2 - Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/28760976/Elevated_IOP_alters_the_space_time_profiles_in_the_center_and_surround_of_both_ON_and_OFF_RGCs_in_mouse_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=28760976 DB - PRIME DP - Unbound Medicine ER -