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Ahmad Zhour, Christian Grimm, Marijana Samardzija, Tobias Peters, Torsten Strasser, Sylvia Bolz, Bernhard H. F. Weber, Eberhart Zrenner, M. Dominik Fischer; In Vivo Analysis Reveals Novel Aspects of Retinal Disease Progression in Rsh1-/Y Mice but no Therapeutic Effect of Carbonic Anhydrase Inhibition. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1134.
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© ARVO (1962-2015); The Authors (2016-present)
X-linked juvenile retinoschisis (XLRS) is the most common juvenile maculopathy in men and is caused by mutations in the gene encoding retinoschisin (RS1). Evidence in the literature on the therapeutic effect of carboanhydrase inhibitors (CAIs) to treat schisis formation in the retina has remained equivocal. Here, we evaluate the effect of the CAI dorzolamide on the structural and functional disease progression in the mouse model for XLRS (Rs1h-/y).
Rs1h-/y mice were treated unilaterally with dorzolamide eye drops (Trusopt® 20mg/ml) every 12 hours for 2 weeks starting on postnatal day 14 (n=27). Changes of retinal structure were monitored by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography at the age of 4, 6, 8, 12 weeks and 7 months. Changes in inner retinal thickness (IRT, as measure of schisis formation) and outer retinal thickness (ORT, as measure of photoreceptor degeneration) were quantified at all time-points. ERG was performed at the age of 8 and 12 weeks. At each time point two mice were sacrificed for histology.
Schisis formation (peak at 3 months) preceded photoreceptor degeneration and hyperfluorescence (peak at 7 months). Structural pathology was most severe in the superior hemiretina. Quantitative analysis showed no significant differences regarding the inner or outer retinal thickness of the treated vs. untreated eyes (IRTOS-OD = -1.29±1.45μm; ORTOS-OD = 0.61±1.34μm; mean±95%CI). Retinal function showed no statistical significant treatment effect in amplitudes (a-waveOS-OD = 5.87±27.04μV; b-waveOS-OD = 0.82±27.81μV).
Time line analysis after treatment with CAIs failed to show short-term, intermediate or long-term evidence of structural as well as functional improvement in Rs1h-/y mice. Schisis formation in the inner retina peaked at the age of 3 months and was followed by photoreceptor degeneration and hyperfluorescence suggesting photoreceptor debris accumulation. Schisis formation and hyperfluorescent spots were more severe in the superior hemiretina.
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