Sarpogrelate, a 5-HT2A receptor antagonist, protects the retina from light-induced retinopathy

Brandon E. Tullis, Renee C. Ryals, Aaron S. Coyner, Michael J. Gale, Alex Nicholson, Cristy Ku, Dain Regis, Wrik Sinha, Shreya Datta, Yuquan Wen, Paul Yang, Mark E. Pennesi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

PURPOSE. To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is protective against light-induced retinopathy in BALB/c mice. METHODS. BALB/c mice were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24, and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48 hours after exposure. Additionally, a single injection regimen was evaluated by injecting mice with 50 mg/kg sarpogrelate once immediately prior to light exposure. To investigate the potential for additive effects of serotonin receptor agents, a combination therapy consisting of sarpogrelate (15 mg/kg) and 8-OH-DPAT (1 mg/kg) was evaluated with the 5-day treatment regimen. Neuroprotection was characterized by the preservation of retinal thickness and function, measured by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), respectively. RESULTS. Mice that were light damaged and injected with saline had significantly reduced outer retinal thickness, total retinal thickness, and ERG amplitudes compared with naïve mice. A 5- day administration of 15, 30, or 40 mg/kg of sarpogrelate was able to partially protect retinal morphology and full protection of retinal morphology was achieved with a 50 mg/kg dose. Both 15 and 30 mg/kg doses of sarpogrelate partially preserved retinal function measured by ERG, whereas 40 and 50 mg/kg doses fully preserved retinal function. Additionally, a single administration of 50 mg/kg sarpogrelate was able to fully preserve both retinal morphology and function. Administration of 15 mg/kg of sarpogrelate and 1 mg/kg of 8-OH-DPAT together demonstrated an additive effect and fully preserved retinal morphology. CONCLUSIONS. A 5- or 1-day treatment with 50 mg/kg sarpogrelate can completely protect the retina of BALB/c mice from light-induced retinopathy. Partial protection can be achieved with lower doses starting at 15 mg/kg and protection increases in a dose-dependent manner. Treatment with low doses of sarpogrelate and 8-OH-DPAT elicits an additive effect that results in full protection of retinal morphology.

Original languageEnglish (US)
Pages (from-to)4560-4569
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number8
DOIs
StatePublished - 2015

Keywords

  • 5-HT receptor
  • Anplag
  • Light-induced retinopathy
  • MCI-9042
  • Neuroprotection
  • Retinal degeneration
  • Sarpogrelate
  • Serotonin

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Tullis, B. E., Ryals, R. C., Coyner, A. S., Gale, M. J., Nicholson, A., Ku, C., Regis, D., Sinha, W., Datta, S., Wen, Y., Yang, P., & Pennesi, M. E. (2015). Sarpogrelate, a 5-HT2A receptor antagonist, protects the retina from light-induced retinopathy. Investigative Ophthalmology and Visual Science, 56(8), 4560-4569. https://doi.org/10.1167/iovs.15-16378