title: Induction of apoptosis of rabbit corneal endothelial cells by preservative-free lidocaine hydrochloride 2%, ropivacaine 1%, or levobupivacaine 0.75%.
abstract: OBJECTIVE
  To determine and compare the amount of apoptosis and changes in rabbit corneal endothelial cell morphology after intracameral administration of different anesthetic agents.
  
  
  METHODS
  Department of Ophthalmology, Baskent University Medical Faculty, Ankara, Turkey.
  
  
  METHODS
  Right eyes of 64 Vienna white rabbits were injected intracamerally with preservative-free lidocaine hydrochloride 2%, ropivacaine 1%, levobupivacaine 0.75%, or fortified balanced salt solution (BSS Plus) (control). Animals were humanely killed 1 day or 7 days later. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling was used to detect apoptosis. Corneal endothelial cells and apoptotic cells were counted by light microscopy. The morphologic appearance was determined by transmission electron microscopy (TEM).
  
  
  RESULTS
  Apoptotic cell density was high in the anesthetic groups on day 1 (P<.01); there was no significant difference between groups at 7 days. Apoptotic cell density declined significantly between 1 day and 7 days in the anesthetic groups (P<.05) but not in the control group. There was no difference in endothelial cell density between the 4 groups at 1 or 7 days. All anesthetic groups showed degenerative changes on TEM, with the least change in the preservative-free lidocaine hydrochloride 2% group.
  
  
  CONCLUSIONS
  Intracameral injections of preservative-free lidocaine, ropivacaine, and levobupivacaine induced significantly more apoptotic endothelial cell loss than BSS Plus and led to morphologic changes in the corneal endothelial cells in the early period. This effect was temporary, with recovery by 7 days. Considering the limited proliferative capacity in human eyes, the induced apoptosis might result in the permanent cell loss and enlargement in human corneal endothelium.
authors.affiliation: Department of Ophthalmology, Baskent University School of Medicine, Ankara, Turkey. borazan74@hotmail.com
authors.forename: Mehmet
authors.initials: M
authors.lastname: Borazan
authors.forename: Aylin
authors.initials: A
authors.lastname: Karalezli
authors.forename: Sibel
authors.initials: S
authors.lastname: Oto
authors.forename: Yonca Aydin
authors.initials: YA
authors.lastname: Akova
authors.forename: Gulten
authors.initials: G
authors.lastname: Karabay
authors.forename: Alper
authors.initials: A
authors.lastname: Kocbiyik
authors.forename: Bulent
authors.initials: B
authors.lastname: Celasun
authors.forename: Beyhan
authors.initials: B
authors.lastname: Demirhan
mesh_terms: D000577:Amides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000633:toxicity; D002452:Cell Count; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure*; D020287:In Situ Nick-End Labeling; D000077554:Levobupivacaine; D008012:Lidocaine / Q000633:toxicity*; D008854:Microscopy, Electron; D011310:Preservatives, Pharmaceutical; D011817:Rabbits; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D011310:Preservatives, Pharmaceutical; D000077212:Ropivacaine; D008012:Lidocaine; D000077554:Levobupivacaine; D002045:Bupivacaine