Intravitreal Docosahexaenoic Acid in a Rabbit Model: Preclinical Safety Assessment

Fecha de publicación: 08/05/2014

Autores de IIS La Fe

• Rosa Dolz Marco

  Autor

• Roberto Gallego Pinazo

  Autor

• María Dolores Pinazo Durán

  Autor

• María Sheila Pons Vazquez

  Autor

• Manuel Díaz Llopis

  Autor

Participantes ajenos a IIS La Fe

• Domingo-Pedro JC

Grupos

• Biomedicina Molecular, Celular y Genómica

  

  Leader

  José María Millán Salvador

Abstract

Purpose: The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. Methods: Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 mu l, 5 mg/50 mu l, 2'5 mg/50 mu l, 50 mu g/50 mu l, 25 mu g/50 mu l, and 5 mu g/50 ml. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological 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 was performed by SPSS 21.0. Results: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 mu l, 5 mg/50 mu l, 2'5 mg/50 mu) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 mg/50 ml. Conclusions: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 mu g/50 mu l. 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.