title: Retinal toxicity of intravitreal genistein in a rabbit model.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the preclinical safety of intravitreal genistein in rabbit eyes over a short-term period.
  
  
  METHODS
  Twelve New Zealand albino rabbits were selected for this study. Four concentrations of genistein (LC Laboratories, Woburn, MA) were prepared: 24 mg/0.1 mL, 135 mg/0.1 mL, 270 mg/0.1 mL, and 540 mg/0.1 mL. Each concentration was injected intravitreally in one eye of three rabbits. As a control, the vehicle solution was injected into the other eye of each animal. Retinal safety of intravitreal genistein was studied with electroretinography and histologic examination in rabbits. Electroretinography recordings were made before the injection and 3 weeks after the injection. Eventually, the rabbits were killed and the retinas were examined by light microscopy. Immunohistochemical staining with caspase-3 and caspase-9 was also performed to evaluate apoptotic expression in all study and control eyes.
  
  
  RESULTS
  Electroretinography studies showed no significant difference between control and genistein-injected eyes at any of the doses in the rabbit model. Histologic examination showed no retinal abnormality in the rabbits injected with different concentrations of genistein. Immunohistochemical staining with caspase-3 and caspase-9 showed no different apoptotic protein expression in any study or control eyes.
  
  
  CONCLUSIONS
  Our results indicate that genistein is a safe intravitreal drug in the rabbit model up to 540 mg. If proven safe and efficacious in human studies, intravitreal injection of genistein could be considered a treatment alternative for ocular neovascularisation in selected cases.
authors.affiliation: Department of Ophthalmology, Eye Clinic, University of Perugia, Perugia, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Fiore
authors.forename: Barbara
authors.initials: B
authors.lastname: Iaccheri
authors.forename: Francesca
authors.initials: F
authors.lastname: Pietrolucci
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giansanti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cavaliere
authors.forename: Renato
authors.initials: R
authors.lastname: Coltella
authors.forename: Maria G
authors.initials: MG
authors.lastname: Mameli
authors.forename: Sofia
authors.initials: S
authors.lastname: Androudi
authors.forename: Periklis
authors.initials: P
authors.lastname: Brazitikos
authors.forename: Carlo
authors.initials: C
authors.lastname: Cagini
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004596:Electroretinography / Q000187:drug effects*; D019833:Genistein / Q000633:toxicity*; D058449:Intravitreal Injections; D023421:Models, Animal; D048789:Phytoestrogens / Q000633:toxicity*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
chemical_list: D016588:Anticarcinogenic Agents; D048789:Phytoestrogens; D019833:Genistein; D053148:Caspase 3; D053453:Caspase 9