Expression of CCR5 and its ligands CCL3, -4, and -5 in the tear film and ocular surface of patients with dry eye disease.
OBJECTIVE
To evaluate the expression of CCR5 and its ligands CCL3, CCL4, and CCL5 in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease.


METHODS
The concentrations of CCL3, CCL4, and CCL5 were measured using enzyme-linked immunosorbent assay in tear samples obtained from forty-three patients with dry eye (17 SS and 26 non-SS patients) and 20 control subjects. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. Expression of the chemokines and their receptor in the conjunctiva was evaluated using immunohistochemistry. Flow cytometry was performed to detect CCR4+CD4+, CCR5+CD4+, and CCR6+CD4+ cells in the conjunctiva.


RESULTS
The concentrations of CCL3, CCL4, and CCL5 were 25.3 ± 24.2, 4.65 ± 3.21, and 93.12 ± 26.31 pg/mL in control subjects, 92.33 ± 13.23, 263.13 ± 116.13, and 253.64 ± 46.29 pg/mL in patients with non-SS, and 215.56 ± 36.1, 697.85 ± 185.65, and 456.12 ± 92.82 pg/mL in patients with SS. The concentrations showed a significant increase in tears of SS patients compared with those of non-SS patients and control subjects (p < 0.05). CCL5 levels showed significant correlation with tear film break-up time, basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (p < 0.01). Staining for the chemokines and their receptor increased in dry eye patients, especially in those with SS patients. Flow cytometry demonstrated increased numbers of CCR5+CD4+, and CCR6+CD4+ cells in dry eye patients in contrast to CCR4+CD4+ cells.


CONCLUSIONS
Expression of CCR5 and its ligands CCL3, CCL4, and CCL5 increase in the tear film and ocular surface of patients with dry eye syndrome, especially in those with SS. CCL5 levels correlate significantly with various tear film and ocular surface parameters.
Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwang-Ju, Korea.
Won
W
Choi
Zhengri
Z
Li
Han-Jin
HJ
Oh
Seong-Kyu
SK
Im
Seung-Hyun
SH
Lee
Soo-Hyun
SH
Park
In-Cheon
IC
You
Kyung-Chul
KC
Yoon
D000328:Adult; D000368:Aged; D015415:Biomarkers; D054405:Chemokine CCL3 / Q000096:biosynthesis*; D054407:Chemokine CCL4 / Q000096:biosynthesis*; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D003228:Conjunctiva / Q000378:metabolism*; D015352:Dry Eye Syndromes / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D012720:Severity of Illness Index; D013666:Tears / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; C515429:CCL3 protein, human; C066507:CCL4 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019713:Receptors, CCR5