title: Intravitreal injection of methotrexate in an experimental rabbit model: determination of ultrastructural changes.
abstract: OBJECTIVE
  To investigate the ultrastructural changes of the rabbit retina induced by intravitreal methotrexate injection.
  
  
  METHODS
  Ten New Zealand white rabbits were enucleated bilaterally at different time periods after intravitreal methotrexate injection. One rabbit was used as control group and one rabbit was used as intact group. Histopathological examinations were performed under light and electron microscopy. Early (within first three days after injection) and long-term (one month after serial injections) effects of intravitreal methotrexate on the retina were investigated.
  
  
  RESULTS
  Retinal edema, vacuolization, and disintegration of mitochondria of the retinal cells were observed as early changes. The main long-term effects after serial injections were edema in the photoreceptor, inner nuclear, and ganglionic cell layers. Cellular disorganisation was seen on light microscopy. Electron microscopic examination revealed mitochondrial degeneration and vacuole formation in retinal cells, nuclear degeneration in outer nuclear layer, and membranous whorl formation in photoreceptor and nerve fiber layers.
  
  
  CONCLUSIONS
  High dose intravitreal methotrexate injection may cause significant ultrastructural changes in the rabbit retina in varying severity. This finding may highlight the potential side effects of methotrexate on human retina in higher doses.
authors.affiliation: Department of Ophthalmology, Cukurova University Medical School, Adana, Turkey.
authors.forename: Ebru B
authors.initials: EB
authors.lastname: Ozkan
authors.forename: Altan A
authors.initials: AA
authors.lastname: Ozcan
authors.forename: Hande Taylan
authors.initials: HT
authors.lastname: Sekeroglu
authors.forename: Yurdun
authors.initials: Y
authors.lastname: Kuyucu
authors.forename: Hulya
authors.initials: H
authors.lastname: Ozgun
authors.forename: Sait
authors.initials: S
authors.lastname: Polat
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D058449:Intravitreal Injections; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008854:Microscopy, Electron; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure*; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology*
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate