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Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice.

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.

SUBMITTER: Tao X

PROVIDER: S-EPMC7736214 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe acute biomechanical response of the optic nerve head (ONH) to intraocular pressure (IOP) elevations may serve as a biomarker for the development and progression of glaucoma.ObjectiveTo evaluate the association between visual field loss and the biomechanical response of the ONH to acute transient IOP elevations.Design, setting, and participantsIn this observational study, 91 Chinese patients (23 with primary open-angle glaucoma [POAG], 45 with primary angle-closure glaucoma, and 23 without glaucoma) were recruited from September 3, 2014, through February 2, 2017. Optical coherence tomography scans of the ONH were acquired at baseline and at 2 sequential IOP elevations (0.64 N and then 0.90 N, by applying forces to the anterior sclera using an ophthalmodynamometer). In each optical coherence tomography volume, lamina cribrosa depth (LCD) and minimum rim width (MRW) were calculated. The mean deviation (MD) and the visual field index (VFI), as assessed by automated perimetry, were correlated with IOP-induced changes of LCD and MRW globally and sectorially.Main outcomes and measuresThe LCD, MRW, MD, and VFI.ResultsAmong the 91 patients, 39 (42.9%) were women; the mean (SD) age was 65.48 (7.23) years. In POAG eyes, a greater change in LCD (anterior displacement) was associated with worse MD and VFI (R = -0.64; 95% CI, -0.97 to -0.31; P = .001; and R = -0.57; 95% CI, -0.94 to -0.19; P = .005, respectively) at the first IOP elevation, and a greater reduction in MRW was also associated with worse MD and VFI (first IOP elevation: R = -0.48; 95% CI, -0.86 to -0.09; P = .02; and R = -0.57; 95% CI, -0.94 to -0.20; P = .004, respectively; second IOP elevation: R = -0.56; 95% CI, -0.98 to -0.13; P = .01; and R = -0.60; 95% CI, -1.03 to -0.17; P = .008, respectively), after adjusting for age, sex, and baseline IOP. A correlation was found between the reduction in MRW in the inferior-temporal sector and the corresponding visual field cluster in POAG eyes at the second elevation (? = -0.55; 95% CI, -0.78 to -0.18; P = .006).Conclusions and relevanceThe biomechanical response of the ONH to acute IOP elevations was associated with established visual field loss in POAG eyes, but not in primary angle-closure glaucoma eyes. This suggests that ONH biomechanics may be related to glaucoma severity in POAG and that the 2 glaucoma subgroups exhibit inherently different biomechanical properties.

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Single transient intraocular pressure elevations cause prolonged retinal ganglion cell dysfunction and retinal capillary abnormalities in mice.

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