title: Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.
abstract: OBJECTIVE
  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 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. 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 µl, 5 mg/50 µl, 2'5 mg/50 µ) 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 µg/50 µl.
  
  
  CONCLUSIONS
  Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/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.
authors.affiliation: Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Dolz-Marco
authors.affiliation: Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gallego-Pinazo
authors.affiliation: Ophthalmology Research Unit "Santiago Grisolía", Valencia, Spain; Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Pinazo-Duran
authors.affiliation: Ophthalmology Research Unit "Santiago Grisolía", Valencia, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: Pons-Vázquez
authors.affiliation: Biochemistry and Molecular Biology Department, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Domingo-Pedro
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Llopis
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D007267:Injections; D008297:Male; D011817:Rabbits; D012160:Retina / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D012449:Safety; D023382:Toxicity Tests, Acute; D014822:Vitreous Body / Q000187:drug effects
chemical_list: D004281:Docosahexaenoic Acids