title: Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy.
abstract: OBJECTIVE
  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.
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Tullis
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Renee C
authors.initials: RC
authors.lastname: Ryals
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Coyner
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gale
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Nicholson
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Cristy
authors.initials: C
authors.lastname: Ku
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Dain
authors.initials: D
authors.lastname: Regis
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Wrik
authors.initials: W
authors.lastname: Sinha
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Shreya
authors.initials: S
authors.lastname: Datta
authors.affiliation: Baylor University Medical Center, Dallas, Texas, United States.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Yang
authors.affiliation: Casey Eye Institute Oregon Health & Science University, Portland, Oregon, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Pennesi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D007274:Injections, Intraperitoneal; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012160:Retina / Q000473:pathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013386:Succinates / Q000008:administration & dosage / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence
chemical_list: D011837:Radiation-Protective Agents; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists; D013386:Succinates; C064294:sarpogrelate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin