Effects of Chronic and Acute Intraocular Pressure Elevation on Scotopic and Photopic Contrast Sensitivity in Mice

• Published in: Investigative ophthalmology & visual science 2016-06, Vol.57 (7), p.3077-3087
• Main Authors: van der Heijden, Meike E, Shah, Priya, Cowan, Cameron S, Yang, Zhuo, Wu, Samuel M, Frankfort, Benjamin J
• Format: Article
• Language: English
• Subjects: Animals; Cell Count; Color Vision - physiology; Contrast Sensitivity - physiology; Dark Adaptation - physiology; Disease Models, Animal; Female; Glaucoma; Intraocular Pressure - physiology; Mice; Mice, Inbred C57BL; Ocular Hypertension - physiopathology; Retina - physiopathology; Retinal Ganglion Cells - pathology
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.16-19312

To compare the impact of intraocular pressure (IOP) elevation on scotopic and photopic contrast sensitivity in mice. We chronically elevated the IOP of wild-type mice via injection of polystyrene beads or acutely via injection of highly cohesive sodium hyaluronate. Some eyes with chronically elevated IOP were treated with either topical brimonidine tartrate 0.1% or brinzolamide 1%. Scotopic and photopic contrast sensitivity was assessed at peak spatiotemporal frequencies at multiple time points, with an established optokinetic technique. Retinal ganglion cell (RGC) counts were determined with an antibody to class III beta-tubulin. Correlations among IOP level, RGC count, and scotopic or photopic contrast sensitivity were performed. Six weeks of IOP elevation caused a generalized reduction of photopic contrast sensitivity and a preferential reduction of scotopic contrast sensitivity at peak spatiotemporal frequencies. The administration of brinzolamide but not brimonidine caused a significant reduction in cumulative IOP, whereas brimonidine, but not brinzolamide, prevented RGC loss. Both brimonidine and brinzolamide prevented contrast sensitivity loss, but brimonidine did so at earlier time points and across a wider range of lighting conditions. Following either chronic or acute IOP elevation, scotopic contrast sensitivity was impacted most prominently by IOP level and not by RGC count, while photopic contrast sensitivity was impacted by a combination of factors. It is possible that scotopic-specific retinal circuitry is altered preferentially by IOP elevation, and that changes in scotopic contrast sensitivity will assist with glaucoma detection. Brimonidine appears to prevent RGC loss via an IOP-independent mechanism.