Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model

  • Julia Beutel
  • Christina Schroder
  • Katharina von Hof
  • Dirk Rades
  • Hartwig Kosmehl
  • Thilo Wedel
  • Peter Sieg
  • Gerd Geerling
  • Samer George Hakim
Laboratory Investigation

Abstract

Purpose

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 (α-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 α-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.

Conclusion

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.

Keywords

Amifostine Dry eye Lidocaine Pilocarpine Radiation Tear secretion 

Notes

Acknowledgement

The authors would like to thank Mrs. G. Knebel (Institute of Anatomy, University of Luebeck) for her painstaking assistance in the transmission electron microscopic studies.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Julia Beutel
    • 1
    • 2
  • Christina Schroder
    • 1
  • Katharina von Hof
    • 3
  • Dirk Rades
    • 4
  • Hartwig Kosmehl
    • 5
  • Thilo Wedel
    • 6
  • Peter Sieg
    • 7
  • Gerd Geerling
    • 8
  • Samer George Hakim
    • 7
  1. 1.Department of OphthalmologyUniversity Hospital Schleswig-HolsteinLuebeckGermany
  2. 2.University Eye Hospital, Centre of OphthalmologyEberhard-Karls University of TuebingenTuebingenGermany
  3. 3.Department of Radiology and Nuclear MedicineUniversity Hospital Schleswig-HolsteinLuebeckGermany
  4. 4.Department of Radiation OncologyUniversity Hospital Schleswig-HolsteinLuebeckGermany
  5. 5.Institute of PathologyHelios Medical CentreErfurtGermany
  6. 6.Institute of AnatomyChristian Albrecht University of KielKielGermany
  7. 7.Department of Maxillofacial SurgeryUniversity Hospital Schleswig-HolsteinLuebeckGermany
  8. 8.Department of OphthalmologyUniversity of WürzburgWürzburgGermany

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