Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model
- 112 Downloads
- 9 Citations
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 secretionNotes
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.
References
- 1.Göbbels M (1990) Das trockene Auge. Standortbestimmung und Aussichten. Fortschr Ophthalmol 87:190–197Google Scholar
- 2.Zettinig G, Hanselmayer G, Fueger BJ, Hofman A, Pirich C, Nepp J, Dudszak R (2002) Long-term impairment of the lacrimal glands after radioiodine therapy: a cross-sectional study. Eur J Nucl Med Mol Imaging 29:1428–1432PubMedCrossRefGoogle Scholar
- 3.Bessell EM, Henck JM, Whitelocke RAF, Wright JE (1987) Ocular morbidity after radiotherapy of orbital and conjunctival lymphoma. Eye 1:90–96PubMedGoogle Scholar
- 4.MacFaul PA, Bedford MA (1970) Ocular complications after irradiation. Br J Ophthalmol 54:237–247PubMedGoogle Scholar
- 5.Schroder C, Hakim SG, Collin JR, Sieg P, Geerling G (2003) Long-term follow-up after autologous submandibular gland transplantation in scarring keratoconjunctivitis with absolute dry eyes. Ophthalmologe 100:1079–1084PubMedCrossRefGoogle Scholar
- 6.Hakim SG, Kosmehl H, Lauer I, Nadrowitz R, Wedel T, Sieg P (2005) A comparative study on the protection profile of lidocaine, amifostine, and pilocarpin on the parotid gland during radiotherapy. Cancer Res 65:10486–10493PubMedCrossRefGoogle Scholar
- 7.Kumar S, Tyler AB, Philipps S, Burnet NG (1997) Oral pilocarpine improves radiotherapy-induced dry eyes. Clin Oncol 9:62–63CrossRefGoogle Scholar
- 8.Hakim SG, Geerling G, Lauer I, Sieg P (2002) Scintigraphic evaluation of lacrimal glands using a rabbit experimental model. Ophthalmic Res 34:254–257PubMedCrossRefGoogle Scholar
- 9.Stephens LC, Schultheiss TE, Ang KK, Peters LJ (1989) Pathogenesis of radiation injury to the salivary glands and potential methods of protection. Cancer Bull 41(2)Google Scholar
- 10.Letschert JGJ, González D, Oskam J, Koorneef L, van Dijk JD, Boukes R, Bras J, van Heerde P, Bartelink H (1991) Results of radiotherapy in patients with stage I orbital non-Hodgkins lymphoma. Radiother Oncol 22:36–44PubMedCrossRefGoogle Scholar
- 11.Solans R, Bosch JA, Porta F, Roselló J, Selva-O’Callagan A, Vilardell M (2001) Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J Nucl Med 42:738–743PubMedGoogle Scholar
- 12.Coppes RP, Vissink A, Zeilstra LJ, Konings AW (1997) Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage. Int J Radiat Biol 72:615–625PubMedCrossRefGoogle Scholar
- 13.Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL 3rd, Tran-Johnson TK, Muscoplat CC, Trivedi M, Goldlust B, Gallagher SC (1999) Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjörgen syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med 159:174–181PubMedCrossRefGoogle Scholar
- 14.Johnson JT, Ferretti GA, Nethery WJ, Valdez IH, Fox PC, Ng D, Muscoplat CC, Gallagher SC (1993) Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med 329:390–395PubMedCrossRefGoogle Scholar
- 15.Coppes RP, Zeilstra LJ, Kampinga HH, Konings AW (2001) Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists. Br J Cancer 28:1055–1063CrossRefGoogle Scholar
- 16.Roesink JM, Konings AW, Terhaard CH, Battermann JJ, Kampinga HH, Coppes RP (1999) Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms. Int J Radiat Oncol Biol Phys 45:483–489PubMedCrossRefGoogle Scholar
- 17.Jones PL, Boudreau N, Myers CA, Erickson HP, Bissell MJ (1995) Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments. J Cell Sci 108:519–527PubMedGoogle Scholar
- 18.Stephens LC, Schultheiss TE, Small SM, Ang KK, Peters LJ (1989) Response of parotid gland organ culture to radiation. Radiat Res 120:140–153PubMedCrossRefGoogle Scholar
- 19.Pratt NE, Sodicoff M, Liss J, Davis M, Sinesi M (1980) Radioprotection of the rat parotid gland by WR-2721: morphology at 60 days post-irradiation. Int J Radiat Oncol Biol Phys 6:431–435PubMedGoogle Scholar
- 20.Bennett CL, Lane D, Stinson T, Glatzel M, Buntzel J (2001) Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany. Cancer Invest 19:107–113PubMedCrossRefGoogle Scholar
- 21.Hay EM, Thomas E, Hajeer A, Chambers H, Silman AJ (1998) Weak association between subjective symptoms of and objective testing for dry eye and dry mouth: results from a population based study. Ann Rheum Dis 57:20–24PubMedCrossRefGoogle Scholar