Expression of sodium iodide symporter in the lacrimal drainage system: implication for the mechanism underlying nasolacrimal duct obstruction in I(131)-treated patients.
OBJECTIVE
Nasolacrimal outflow obstruction has been associated with high-dose (>150 mCi) radioactive iodine (I(131)) treatment. Commonly used for thyroid cancer treatment, I(131) is effectively transported in the targeted tissue by the Na(+)/I symporter (NIS). We hypothesized that NIS is expressed in the lacrimal sac and nasolacrimal duct and that active accumulation of I(131) is responsible for the clinical observations seen in these patients.


METHODS
Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were used to evaluate NIS expression in both archived and fresh human tissues


RESULTS
Reverse transcriptase-polymerase chain reaction analysis showed that NIS mRNA is present in the lacrimal sac. Immunohistochemical analysis indicated that NIS protein is expressed in the stratified columnar epithelial cells of the lacrimal sac and nasolacrimal duct. NIS protein was undetectable in the lacrimal gland, Wolfring and Krause glands, conjunctiva, canaliculus, and nasal mucosa. NIS-expressing columnar epithelial cells were absent and fibrosis was evident in the lacrimal sacs from I(131)-treated patients undergoing dacryocystorhinostomy.


CONCLUSIONS
NIS is present in the lacrimal sac and nasolacrimal duct of humans, correlating to the anatomic areas of clinical obstruction that develop in patients treated with greater than 150 mCi of I(131). This suggests that NIS may be the vector of radiation-induced injury to the lacrimal system. To our knowledge, this is the first report of any ion transporter in the nasolacrimal outflow system and raises new questions as to the role the lacrimal sac plays in the modification of tears and in lacrimal outflow pathology.
Morgenstern
Kenneth E
KE
Department of Ophthalmology, Division of Oculoplastic Surgery, The Ohio State University, Columbus, OH, USA. kmorgenstern@pol.net
Vadysirisack
Douangsone D
DD
Zhang
Zhaoxia
Z
Cahill
Kenneth V
KV
Foster
Jill A
JA
Burns
John A
JA
Kloos
Richard T
RT
Jhiang
Sissy M
SM
D001485:Basement Membrane / Q000378:metabolism / Q000528:radiation effects; D003608:Dacryocystorhinostomy; D004847:Epithelial Cells / Q000378:metabolism* / Q000528:radiation effects; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D007765:Lacrimal Apparatus / Q000378:metabolism / Q000528:radiation effects; D007767:Lacrimal Duct Obstruction / Q000209:etiology / Q000378:metabolism*; D009301:Nasolacrimal Duct / Q000378:metabolism* / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters