Evaluación preclínica de la toxicidad retiniana en la administración intravítrea de ácido docosahexaenoico en modelo experimental de conejo

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Publication date
2013
Reading date
15-04-2013
Advisors
Díaz Llopis, Manuel
Pinazo Durán, María Dolores
Gallego Pinazo, Roberto
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Abstract
Purpose: to evaluate the retinal toxicity of a unit dose of intravítrea pure docosahexaenoico acid (DHA) in rabbit eyes over a short-term period. Methods: Sixteen New Zealand albino rabbits were selected for this toxicology pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelone, Spain) were prepared: 10mg/50 μL, 5mg/50 μL, 2’5mg/50 μL, 50μg/50 μL, 25μg/50 μL, and 5μg/50 μL. Each concentration was injected intravitreally in one eye of two rabbits. As a control, the vehicle solution was injected into one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intreavitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histologic examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis were performed by SPSS 21.0 3 Rosa Dolz Marco Abstract Results: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10mg/50μl, 5mg/50μl, 2'5mg/50μ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected results at any of the concentrations except for the group injected with 50μg/50. Conclusions: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25μg/50 μL. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination of different retinal diseases.
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