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Simon Topp Christensen, Kristian Agmund Haanes, Michael Larsen; Possible new in vivo experimental model for normal-tension glaucoma. Invest. Ophthalmol. Vis. Sci. 2020;61(9):PB0067.
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Preclinical in vivo experimental models for normal-tension glaucoma (NTG) are relevant for imaging studies. We tested the hypothesis that a retinal ischemia model of male pigmented outbred Long Evans rats subjected to a single intravitreal injection of endothelin-1 (ET-1), a potent vasoconstrictor, would result in an NTG phenotype.
The rats received a single bolus by IVT injection of 5μL 500μM ET-1 into the right eye (RE)(N=3), with the left eye (LE) being used as an internal control. The rats were imaged by ultrahigh-resolution polarization-sensitive optical coherence tomography (UHR-SD-OCT) system, developed as part of the EU project GALAHAD (Project ref.732613). Imaging times included Day0 (day of injection), Day3, Day28 and Day60, while the retinal layer thicknesses were evaluated using Insight image segmentation software (Phoenix Research Laboratories). Intraocular pressure (IOP) measurements were performed on conscious rats before injection of ET-1 and at Days 1, 2 and 7 after injection, using an Icare Tonolab rebound tonometer. Two-way repeated measures ANOVA with Geisser-Greenhouse correction for sphericity and Holm-Sidak post-tests were used for statistical analysis.
Our results showed that intravitreal injection of ET-1 lead to an increase in inner retina (IR) thickness (138.3±3.2% of baseline, p= 0.0131) and total retina (TR) thickness (118.3±0.7%, p= 0.0025) from Day0 to Day3 in the RE. We also observed a trend of thinning of the inner retina at Day28 (84.7±7.8%) and Day60 (89.7±12.1%). Comparing the RE and LE at Day3, we also observed a significant increase in the IR thickness (135.0±0.9%, p= 0.0181) and TR thickness (118.0±2.0%, p=0.0265) of the RE. We observed a reduced mean IOP in the RE, with 17.8 mmHg at baseline to 9.3 mmHg at Day1 and 9.7 mmHg at Day2. The IOP returned to pre-injection levels by Day7.
Our results showed no increased IOP, consistent with NTG, while the decrease in IOP at Day1 could be due to vasoconstriction by ET-1. After a transient ischemic edema, reduction of the retina due to loss of tissue in the inner layers of the retina, notably the retinal nerve fiber layer, was seen to a degree that was beyond the thickness resolution limit of the OCT instrument. We conclude that the ET-1 model is suitable for the induction of NTG-like inner retinal damage that can be used to test the sensitivity of an OCT instrument designed for the monitoring of glaucoma.
This is a 2020 Imaging in the Eye Conference abstract.
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