TY - JOUR
T1 - Sarpogrelate, a 5-HT2A receptor antagonist, protects the retina from light-induced retinopathy
AU - Tullis, Brandon E.
AU - Ryals, Renee C.
AU - Coyner, Aaron S.
AU - Gale, Michael J.
AU - Nicholson, Alex
AU - Ku, Cristy
AU - Regis, Dain
AU - Sinha, Wrik
AU - Datta, Shreya
AU - Wen, Yuquan
AU - Yang, Paul
AU - Pennesi, Mark E.
N1 - Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - 5-HT receptor
KW - Anplag
KW - Light-induced retinopathy
KW - MCI-9042
KW - Neuroprotection
KW - Retinal degeneration
KW - Sarpogrelate
KW - Serotonin
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U2 - 10.1167/iovs.15-16378
DO - 10.1167/iovs.15-16378
M3 - Article
C2 - 26200496
AN - SCOPUS:84939824107
SN - 0146-0404
VL - 56
SP - 4560
EP - 4569
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 8
ER -