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Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice.
Exp Eye Res. 2015 Jan; 130:29-37.EE

Abstract

The purpose of this study was to assess the impact of prolonged intraocular pressure (IOP) elevation on retinal anatomy and function in a mouse model of experimental glaucoma. IOP was elevated by anterior chamber injection of a fixed combination of polystyrene beads and sodium hyaluronate, and maintained via re-injection after 24 weeks. IOP was measured weekly with a rebound tonometer for 48 weeks. Histology was assessed with a combination of retrograde labeling and antibody staining. Retinal physiology and function was assessed with dark-adapted electroretinograms (ERGs). Comparisons between bead-injected animals and various controls were conducted at both 24 and 48 weeks after bead injection. IOP was elevated throughout the study. IOP elevation resulted in a reduction of retinal ganglion cell (RGCs) and an increase in axial length at both 24 and 48 weeks after bead injection. The b-wave amplitude of the ERG was increased to the same degree in bead-injected eyes at both time points, similar to previous studies. The positive scotopic threshold response (pSTR) amplitude, a measure of RGC electrical function, was diminished at both 24 and 48 weeks when normalized to the increased b-wave amplitude. At 48 weeks, the pSTR amplitude was reduced even without normalization, suggesting more profound RGC dysfunction. We conclude that injection of polystyrene beads and sodium hyaluronate causes chronic IOP elevation which results in phenotypes of stable b-wave amplitude increase and progressive pSTR amplitude reduction, as well as RGC loss and axial length elongation.

Authors+Show Affiliations

Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; School of Optometry, Hong Kong Polytechnic University, Hong Kong.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA. Electronic address: benjamin.frankfort@bcm.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25450059

Citation

Khan, A Kareem, et al. "Prolonged Elevation of Intraocular Pressure Results in Retinal Ganglion Cell Loss and Abnormal Retinal Function in Mice." Experimental Eye Research, vol. 130, 2015, pp. 29-37.
Khan AK, Tse DY, van der Heijden ME, et al. Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. Exp Eye Res. 2015;130:29-37.
Khan, A. K., Tse, D. Y., van der Heijden, M. E., Shah, P., Nusbaum, D. M., Yang, Z., Wu, S. M., & Frankfort, B. J. (2015). Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. Experimental Eye Research, 130, 29-37. https://doi.org/10.1016/j.exer.2014.11.007
Khan AK, et al. Prolonged Elevation of Intraocular Pressure Results in Retinal Ganglion Cell Loss and Abnormal Retinal Function in Mice. Exp Eye Res. 2015;130:29-37. PubMed PMID: 25450059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. AU - Khan,A Kareem, AU - Tse,Dennis Y, AU - van der Heijden,Meike E, AU - Shah,Priya, AU - Nusbaum,Derek M, AU - Yang,Zhuo, AU - Wu,Samuel M, AU - Frankfort,Benjamin J, Y1 - 2014/11/18/ PY - 2014/07/09/received PY - 2014/10/24/revised PY - 2014/11/12/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/2/19/medline KW - Electroretinogram (ERG) KW - Glaucoma KW - Intraocular pressure (IOP) KW - Microbead KW - Retinal ganglion cell KW - Scotopic threshold response (STR) SP - 29 EP - 37 JF - Experimental eye research JO - Exp Eye Res VL - 130 N2 - The purpose of this study was to assess the impact of prolonged intraocular pressure (IOP) elevation on retinal anatomy and function in a mouse model of experimental glaucoma. IOP was elevated by anterior chamber injection of a fixed combination of polystyrene beads and sodium hyaluronate, and maintained via re-injection after 24 weeks. IOP was measured weekly with a rebound tonometer for 48 weeks. Histology was assessed with a combination of retrograde labeling and antibody staining. Retinal physiology and function was assessed with dark-adapted electroretinograms (ERGs). Comparisons between bead-injected animals and various controls were conducted at both 24 and 48 weeks after bead injection. IOP was elevated throughout the study. IOP elevation resulted in a reduction of retinal ganglion cell (RGCs) and an increase in axial length at both 24 and 48 weeks after bead injection. The b-wave amplitude of the ERG was increased to the same degree in bead-injected eyes at both time points, similar to previous studies. The positive scotopic threshold response (pSTR) amplitude, a measure of RGC electrical function, was diminished at both 24 and 48 weeks when normalized to the increased b-wave amplitude. At 48 weeks, the pSTR amplitude was reduced even without normalization, suggesting more profound RGC dysfunction. We conclude that injection of polystyrene beads and sodium hyaluronate causes chronic IOP elevation which results in phenotypes of stable b-wave amplitude increase and progressive pSTR amplitude reduction, as well as RGC loss and axial length elongation. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/25450059/Prolonged_elevation_of_intraocular_pressure_results_in_retinal_ganglion_cell_loss_and_abnormal_retinal_function_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(14)00303-0 DB - PRIME DP - Unbound Medicine ER -