Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model.
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.
Beutel
Julia
J
Department of Ophthalmology, University Hospital Schleswig-Holstein, Luebeck, Germany. julia.beutel@med.uni-tuebingen.de
Schroder
Christina
C
von Hof
Katharina
K
Rades
Dirk
D
Kosmehl
Hartwig
H
Wedel
Thilo
T
Sieg
Peter
P
Geerling
Gerd
G
Hakim
Samer George
SG
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
D000199:Actins; D011837:Radiation-Protective Agents; D019063:Tenascin; D010862:Pilocarpine; D008012:Lidocaine; D004999:Amifostine