Tags

Type your tag names separated by a space and hit enter

Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice.
Proc Natl Acad Sci U S A. 2015 Feb 24; 112(8):2593-8.PN

Abstract

Glaucoma is the second leading cause of blindness in the United States and the world, characterized by progressive degeneration of the optic nerve and retinal ganglion cells (RGCs). Glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs in sectored patterns. Recent evidence has suggested that this early sensitivity loss may be associated with dysfunctions in the inner retina, but detailed cellular and synaptic mechanisms underlying such sensitivity changes are largely unknown. In this study, we use whole-cell voltage-clamp techniques to analyze light responses of individual bipolar cells (BCs), AII amacrine cells (AIIACs), and ON and sustained OFF alpha-ganglion cells (ONαGCs and sOFFαGCs) in dark-adapted mouse retinas with elevated intraocular pressure (IOP). We present evidence showing that elevated IOP suppresses the rod ON BC inputs to AIIACs, resulting in less sensitive AIIACs, which alter AIIAC inputs to ONαGCs via the AIIAC→cone ON BC→ONαGC pathway, resulting in lower ONαGC sensitivity. The altered AIIAC response also reduces sOFFαGC sensitivity via the AIIAC→sOFFαGC chemical synapses. These sensitivity decreases in αGCs and AIIACs were found in mice with elevated IOP for 3-7 wk, a stage when little RGC or optic nerve degeneration was observed. Our finding that elevated IOP alters neuronal function in the inner retina before irreversible structural damage occurs provides useful information for developing new diagnostic tools and treatments for glaucoma in human patients.

Authors+Show Affiliations

Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030.Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030.Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030.Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030 swu@bcm.edu.

Pub Type(s)

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

Language

eng

PubMed ID

25675503

Citation

Pang, Ji-Jie, et al. "Elevated Intraocular Pressure Decreases Response Sensitivity of Inner Retinal Neurons in Experimental Glaucoma Mice." Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 8, 2015, pp. 2593-8.
Pang JJ, Frankfort BJ, Gross RL, et al. Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proc Natl Acad Sci U S A. 2015;112(8):2593-8.
Pang, J. J., Frankfort, B. J., Gross, R. L., & Wu, S. M. (2015). Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proceedings of the National Academy of Sciences of the United States of America, 112(8), 2593-8. https://doi.org/10.1073/pnas.1419921112
Pang JJ, et al. Elevated Intraocular Pressure Decreases Response Sensitivity of Inner Retinal Neurons in Experimental Glaucoma Mice. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2593-8. PubMed PMID: 25675503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. AU - Pang,Ji-Jie, AU - Frankfort,Benjamin J, AU - Gross,Ronald L, AU - Wu,Samuel M, Y1 - 2015/02/09/ PY - 2015/2/13/entrez PY - 2015/2/13/pubmed PY - 2015/5/2/medline KW - AII amacrine cells KW - bipolar cells KW - ganglion cells KW - glaucoma KW - intraocular pressure SP - 2593 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 112 IS - 8 N2 - Glaucoma is the second leading cause of blindness in the United States and the world, characterized by progressive degeneration of the optic nerve and retinal ganglion cells (RGCs). Glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs in sectored patterns. Recent evidence has suggested that this early sensitivity loss may be associated with dysfunctions in the inner retina, but detailed cellular and synaptic mechanisms underlying such sensitivity changes are largely unknown. In this study, we use whole-cell voltage-clamp techniques to analyze light responses of individual bipolar cells (BCs), AII amacrine cells (AIIACs), and ON and sustained OFF alpha-ganglion cells (ONαGCs and sOFFαGCs) in dark-adapted mouse retinas with elevated intraocular pressure (IOP). We present evidence showing that elevated IOP suppresses the rod ON BC inputs to AIIACs, resulting in less sensitive AIIACs, which alter AIIAC inputs to ONαGCs via the AIIAC→cone ON BC→ONαGC pathway, resulting in lower ONαGC sensitivity. The altered AIIAC response also reduces sOFFαGC sensitivity via the AIIAC→sOFFαGC chemical synapses. These sensitivity decreases in αGCs and AIIACs were found in mice with elevated IOP for 3-7 wk, a stage when little RGC or optic nerve degeneration was observed. Our finding that elevated IOP alters neuronal function in the inner retina before irreversible structural damage occurs provides useful information for developing new diagnostic tools and treatments for glaucoma in human patients. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/25675503/Elevated_intraocular_pressure_decreases_response_sensitivity_of_inner_retinal_neurons_in_experimental_glaucoma_mice_ DB - PRIME DP - Unbound Medicine ER -