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Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice.
Exp Eye Res. 2020 12; 201:108296.EE

Abstract

Transient intraocular pressure (IOP) elevations are likely to occur in certain forms of glaucoma and after intravitreal injections to treat various retinal diseases. However, the impact of these transient IOP elevations on the physiology of individual retinal ganglion cells (RGCs) is unknown. In this report, we explore how transient IOP elevations in mice affect RGC physiology, RGC anatomy, and retinal arteriole and capillary structure. Transient IOP elevation was induced in 12-week old wild type C57BL6J mice by injecting sodium hyaluronate into the anterior chamber. IOP was measured immediately after the injection and again 1 and 7 days later. Average peak IOP after injection was ~50 mmHg and subsequent IOPs returned to normal. RGC physiology was assessed with a multielectrode array (MEA) by calculating a spike triggered average (STA) at the same time points. RGC counts and retinal vascular structure were assessed 14 days after injection with immunohistochemistry to label RGCs and blood vessels. Transient IOP elevation caused a marked reduction of scotopic STA presence and delayed center and surround STA peak times that did not recover. Transient IOP elevation also caused a reduced photopic receptive field size and spontaneous firing rate, both of which showed some recovery with time. Transient IOP elevation also induced vascular remodeling: the number of capillary branches was decreased within the superficial and intermediate vascular plexi. RGC counts, retinal arteriole diameter, and deep capillary plexus branching were unaffected. These previously unappreciated findings suggest that transient IOP elevation may cause unrecognized and potentially long-term pathology to RGCs and associated neurovascular units which should be accounted for in clinical practice.

Authors+Show Affiliations

Department of Ophthalmology, Baylor College of Medicine, United States.Department of Ophthalmology, Baylor College of Medicine, United States.Department of Ophthalmology, Baylor College of Medicine, United States.Department of Ophthalmology, Baylor College of Medicine, United States.Department of Ophthalmology, Baylor College of Medicine, United States; Department of Neuroscience, Baylor College of Medicine, United States. Electronic address: benjamin.frankfort@bcm.edu.

Pub Type(s)

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

Language

eng

PubMed ID

33039455

Citation

Tao, Xiaofeng, et al. "Single Transient Intraocular Pressure Elevations Cause Prolonged Retinal Ganglion Cell Dysfunction and Retinal Capillary Abnormalities in Mice." Experimental Eye Research, vol. 201, 2020, p. 108296.
Tao X, Sigireddi RR, Westenskow PD, et al. Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice. Exp Eye Res. 2020;201:108296.
Tao, X., Sigireddi, R. R., Westenskow, P. D., Channa, R., & Frankfort, B. J. (2020). Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice. Experimental Eye Research, 201, 108296. https://doi.org/10.1016/j.exer.2020.108296
Tao X, et al. Single Transient Intraocular Pressure Elevations Cause Prolonged Retinal Ganglion Cell Dysfunction and Retinal Capillary Abnormalities in Mice. Exp Eye Res. 2020;201:108296. PubMed PMID: 33039455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice. AU - Tao,Xiaofeng, AU - Sigireddi,Rohini R, AU - Westenskow,Peter D, AU - Channa,Roomasa, AU - Frankfort,Benjamin J, Y1 - 2020/10/08/ PY - 2020/06/26/received PY - 2020/09/17/revised PY - 2020/10/06/accepted PY - 2020/10/12/pubmed PY - 2021/3/2/medline PY - 2020/10/11/entrez KW - IOP KW - Intraocular pressure KW - RGC KW - Retinal ganglion cell KW - Retinal vasculature KW - Transient IOP elevation SP - 108296 EP - 108296 JF - Experimental eye research JO - Exp Eye Res VL - 201 N2 - Transient intraocular pressure (IOP) elevations are likely to occur in certain forms of glaucoma and after intravitreal injections to treat various retinal diseases. However, the impact of these transient IOP elevations on the physiology of individual retinal ganglion cells (RGCs) is unknown. In this report, we explore how transient IOP elevations in mice affect RGC physiology, RGC anatomy, and retinal arteriole and capillary structure. Transient IOP elevation was induced in 12-week old wild type C57BL6J mice by injecting sodium hyaluronate into the anterior chamber. IOP was measured immediately after the injection and again 1 and 7 days later. Average peak IOP after injection was ~50 mmHg and subsequent IOPs returned to normal. RGC physiology was assessed with a multielectrode array (MEA) by calculating a spike triggered average (STA) at the same time points. RGC counts and retinal vascular structure were assessed 14 days after injection with immunohistochemistry to label RGCs and blood vessels. Transient IOP elevation caused a marked reduction of scotopic STA presence and delayed center and surround STA peak times that did not recover. Transient IOP elevation also caused a reduced photopic receptive field size and spontaneous firing rate, both of which showed some recovery with time. Transient IOP elevation also induced vascular remodeling: the number of capillary branches was decreased within the superficial and intermediate vascular plexi. RGC counts, retinal arteriole diameter, and deep capillary plexus branching were unaffected. These previously unappreciated findings suggest that transient IOP elevation may cause unrecognized and potentially long-term pathology to RGCs and associated neurovascular units which should be accounted for in clinical practice. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/33039455/Single_transient_intraocular_pressure_elevations_cause_prolonged_retinal_ganglion_cell_dysfunction_and_retinal_capillary_abnormalities_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(20)30554-6 DB - PRIME DP - Unbound Medicine ER -