title: Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model.
abstract: OBJECTIVE
  To evaluate the radioprotective effect of lidocaine, amifostine and pilocarpine on lacrimal glands.
  
  
  METHODS
  Twenty-five rabbits were randomized into five groups: the control, irradiated/sham-treated, irradiated/lidocaine-pretreated, irradiated/amifostine-pretreated and irradiated/pilocarpine-pretreated groups. One week before irradiation, 72 h and 1 month afterward, the inferior lacrimal gland was investigated histomorphologically, immunohistochemically [tenascin-C and alpha smooth muscle actin (alpha-SMA)] and functionally using scintigraphy and the Schirmer test.
  
  
  RESULTS
  Compared with control animals, the lacrimal ejection fraction (LEF) in the irradiated/sham-treated group was significantly reduced 72 h afterwards. Pilocarpine- as well as amifostine-pretreated animals showed a slightly lower reduction. Lidocaine stabilized the LEF. Immunohistochemically, a significant loss of alpha-SMA and an up-regulation of tenascin-C expression in irradiated/untreated glands were evident. Pretreatment with lidocaine and amifostine-but not with pilocarpine-induced lower up-regulation of TN-C expression 72 h after radiation. One month after irradiation a reduction of the immunhistochemical changes at all was found. Ultrastructural damage was observed in irradiated/non-treated and pilocarpine-pretreated glands, whereas lidocaine and amifostine preserved the ultrastructure.
  
  
  CONCLUSIONS
  Morphologic and functional findings could prove a prevailing protection profile of amifostine and especially of lidocaine on lacrimal glands. This may provide a prophylactic approach in the radioprotection of the lacrimal glands during radiotherapy of the orbital region.
authors.affiliation: Department of Ophthalmology, University Hospital Schleswig-Holstein, Luebeck, Germany. julia.beutel@med.uni-tuebingen.de
authors.forename: Julia
authors.initials: J
authors.lastname: Beutel
authors.forename: Christina
authors.initials: C
authors.lastname: Schroder
authors.forename: Katharina
authors.initials: K
authors.lastname: von Hof
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kosmehl
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
authors.forename: Peter
authors.initials: P
authors.lastname: Sieg
authors.forename: Gerd
authors.initials: G
authors.lastname: Geerling
authors.forename: Samer George
authors.initials: SG
authors.lastname: Hakim
mesh_terms: D000199:Actins / Q000378:metabolism; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D008012:Lidocaine / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011877:Radionuclide Imaging; D013666:Tears / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism; D015854:Up-Regulation; D014965:X-Rays
chemical_list: D000199:Actins; D011837:Radiation-Protective Agents; D019063:Tenascin; D010862:Pilocarpine; D008012:Lidocaine; D004999:Amifostine