Expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome.
OBJECTIVE
To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome.


METHODS
Thirty-three patients with dry eye (16 with and 17 without Sjögren's syndrome) and 15 control subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were measured with enzyme-linked immunosorbent assays. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. The expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by using immunohistochemistry. Flow cytometry was performed to count CXCR3(+) cells and CXCR3(+)CD4(+) cells in the conjunctiva.


RESULTS
The concentrations of CXCL9, -10, and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334 pg/mL, in the patients with dry eye, and 272 +/- 269 (P = 0.01), 18,149 +/- 5,266 (P = 0.02), and 486 +/- 175 (P < 0.01) pg/mL in the control subjects, respectively. The concentrations significantly increased in tears of the patients with Sjögren's syndrome compared with those of the patients with non-Sjögren's dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P < 0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry eye, especially in the patients with Sjögren's syndrome. Flow cytometry demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the patients with dry eye.


CONCLUSIONS
Expression of CXCL9, -10, -11, and CXCR3 increased in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.).
Yoon
Kyung-Chul
KC
Department of Ophthalmology, Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School and Hospital, Gwang-Ju, Korea. kcyoon@jnu.ac.kr
Park
Chang-Soo
CS
You
In-Cheon
IC
Choi
Hwan-Jun
HJ
Lee
Kwang-Hoon
KH
Im
Seong-Kyu
SK
Park
Hong-Yong
HY
Pflugfelder
Stephen C
SC
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D054357:Chemokine CXCL10 / Q000378:metabolism*; D054371:Chemokine CXCL11 / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000378:metabolism*; D003228:Conjunctiva / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020397:Goblet Cells / Q000166:cytology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D013666:Tears / Q000378:metabolism*; D055815:Young Adult
C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D005136:Eye Proteins; D054367:Receptors, CXCR3; C042434:tear proteins