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Brandon Ellis Tullis, Michael Joos Gale, Alexander J Nicholson, Michelle Sorensen, Shreya Datta, Mark E Pennesi, Pennesi Lab; Evaluation of the Neuroprotective Potential of the 5HT2A Receptor Antagonist Sarpogrelate Hydrochloride in a Light Damage Model of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1902.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the potential of the 5HT2A receptor antagonist sarpogrelate hydrochloride (MCI-9042; Anplag) for protecting rodent retinal structure and function from light-induced phototoxicity
Albino BALB/c mice received intraperitoneal injections of 5 mg/kg sarpogrelate hydrochloride (5 mice), 50 mg/kg sarpogrelate hydrochloride (5 mice), or 0.9% saline solution (4 mice). The mice received injections 48, 24, and 0 hours prior to light damage, as well as 24 and 48 hours afterward. Light damage was induced by exposing the mice to 9.0-9.4×103 lux from four compact fluorescent light bulbs inside a custom-built light box. The light box was well-ventilated and temperature-controlled, and the mice were checked on each hour to ensure comfort. One week after light damage, retinal structure was viewed in cross-section using spectral domain optical coherence tomography (SD-OCT). Retinal function was analyzed through electroretinography (ERG).
SD-OCT imaging of the high dose sarpogrelate mice showed a marked preservation of retinal structure in comparison to the low dose and saline control mice. The outer nuclear layer was severely thinned in the saline control mice and the low dose sarpogrelate mice, but was only slightly thinned in most retinal quadrants imaged in the high dose sarpogrelate mice. Total retinal thickness was also visibly thicker in the high dose sarpogrelate mice; numeric comparisons of retinal thicknesses will be made available following further analysis. The five low dose sarpogrelate mice did not exhibit a grossly appreciable preservation of retinal structure when compared to the control group. The ERG data followed a similar pattern as the OCT data. The b wave amplitudes of the saline control and low dose sarpogrelate mice were 50% and 37% as large as those seen in normal BALB/c mice, respectively, but the b wave amplitudes of the high dose sarpogrelate mice were 83% of normal on average.
Preliminary evidence indicates that high dose, but not low dose, sarpogrelate hydrochloride appears to be effective in protecting albino BALB/c mouse retinal structure (as measured by OCT) and preserving retinal function (as measured by ERG) from light-induced phototoxicity compared to saline-injected animals.
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