title: Dose-dependent ultrastructural changes in rat cornea after oral methylphenidate administration.
abstract: OBJECTIVE
  To investigate dose-dependent ultrastructural changes in rat cornea after oral methylphenidate Ritalin administration.
  
  
  METHODS
  This study was conducted in the Department of Anatomy, Gazi University Faculty of Medicine, Ankara, Turkey between March and May 2005, with a total of 27 female prepubertal Wistar albino rats, divided into 3 different dose groups 5mg/kg, 10 mg/kg, 20 mg/kg, and their control groups. They were treated orally with methylphenidate, and eye tissue was removed to process for electron microscopic studies.
  
  
  RESULTS
  We observed that all cells, and prominently basal cells of the corneal epithelium show dose-dependent degenerative changes such as apoptotic bodies, chromatin condensation, and ondulation in their nuclei and crystolysis of the mitochondrion. In the stroma, the most evident finding was the increase of the collagen fiber. In addition to dose-dependent changes related to the apoptotic process, which is chromatin condensation in their nuclei, electron dense material accumulation, and pericellular edema in the cytoplasm were also seen. In the endothelial cell lines, disruption of the junctional complexes, vacuolization in the cell cytoplasms, and crystolysis of the mitochondrion's with rough endoplasmic reticulum cisternae activity were observed.
  
  
  CONCLUSIONS
  Ritalin is inducing an evident degeneration, especially in epithelium cells with increasing doses. Ultrastructural cell organelle composition degeneration with stromal fibrosis has a negative effect on cornea dehydration. In light of these findings, we believe that the Ritalin treatment doses need to be kept to a minimum to maintain healthy cornea ultrastructure and related physiology.
authors.affiliation: Department of Anatomy, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Rabet
authors.initials: R
authors.lastname: Gozil
authors.forename: Gulnur
authors.initials: G
authors.lastname: Take
authors.forename: Meltem
authors.initials: M
authors.lastname: Bahcelioglu
authors.forename: Erdinc
authors.initials: E
authors.lastname: Tunc
authors.forename: Hale
authors.initials: H
authors.lastname: Oktem
authors.forename: Guleser
authors.initials: G
authors.lastname: Caglar
authors.forename: Engin
authors.initials: E
authors.lastname: Calguner
authors.forename: Deniz
authors.initials: D
authors.lastname: Erdogan
mesh_terms: D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000648:ultrastructure*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008774:Methylphenidate / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008774:Methylphenidate