Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy.
Invest Ophthalmol Vis Sci
; 56(8): 4560-9, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-26200496
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Traumatismos Experimentales por Radiación
/
Protectores contra Radiación
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Retina
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Degeneración Retiniana
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Succinatos
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Antagonistas del Receptor de Serotonina 5-HT2
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Luz
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos