Kim Yu Jeong, Ryu Jin Suk, Park Se Yeon, Lee Hyun Ju, Ko Jung Hwa, Kim Mee Kum, Wee Won Ryang, Oh Joo Youn
*Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea; and †Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Cornea. 2016 Apr;35(4):536-42. doi: 10.1097/ICO.0000000000000756.
To compare the therapeutic effects of topical tumor necrosis factor (TNF)-α-stimulated gene/protein-6 (TSG-6) with those of cyclosporine and prednisolone eye drops in NOD.B10.H2 mice, a model for inflammation-mediated dry eye.
The 12-week-old NOD.B10.H2 mice were topically administered recombinant TSG-6 (0.1%) 4 times a day, 0.05% cyclosporine (Restasis) twice a day, or 1% prednisolone (Pred Forte) 4 times a day for 1 week. Aqueous tear production was measured by phenol red thread test, and corneal epithelial damage was observed with lissamine green and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Conjunctival goblet cell number was evaluated with periodic acid-Schiff staining. The levels of inflammatory cytokines were analyzed in the ocular surface (cornea and conjunctiva) and intraorbital gland. The dose-dependent effects of topical TSG-6 (0.001, 0.01, and 0.1%) were tested.
Tear production and goblet cell density were significantly increased in all groups receiving TSG-6, cyclosporine, and prednisolone. Corneal epithelial staining was markedly reduced by TSG-6 and cyclosporine but not by prednisolone. In prednisolone-treated eyes, corneal epithelial thickness was decreased, and apoptosis of corneal epithelial cells was increased. The levels of interferon gamma and TNF-α in the ocular surface and intraorbital gland were significantly repressed by TSG-6 and cyclosporine, and prednisolone treatment significantly reduced the level of interferon gamma. The effects of TSG-6 on the ocular surface and tear production were dose dependent.
Topical TSG-6 was as effective in inflammation-mediated dry eye as cyclosporine eye drops. Topical prednisolone suppressed inflammation but induced apoptosis in the corneal epithelium.
在炎症介导的干眼模型NOD.B10.H2小鼠中，比较局部应用肿瘤坏死因子（TNF）-α刺激基因/蛋白-6（TSG-6）与环孢素和泼尼松龙滴眼液的治疗效果。
对12周龄的NOD.B10.H2小鼠，分别每日局部给予重组TSG-6（0.1%）4次、0.05%环孢素（Restasis）2次或1%泼尼松龙（Pred Forte）4次，持续1周。通过酚红棉线试验测量泪液分泌量，用丽丝胺绿和末端脱氧核苷酸转移酶dUTP缺口末端标记染色观察角膜上皮损伤情况。用高碘酸-希夫染色评估结膜杯状细胞数量。分析眼表（角膜和结膜）及眶内腺体中炎性细胞因子的水平。测试局部应用TSG-6（0.001%、0.01%和0.1%）的剂量依赖性效应。
接受TSG-6、环孢素和泼尼松龙治疗的所有组中，泪液分泌和杯状细胞密度均显著增加。TSG-6和环孢素可显著减少角膜上皮染色，但泼尼松龙无此作用。在泼尼松龙治疗的眼中，角膜上皮厚度降低，角膜上皮细胞凋亡增加。TSG-6和环孢素可显著抑制眼表和眶内腺体中干扰素γ和TNF-α的水平，泼尼松龙治疗可显著降低干扰素γ水平。TSG-6对眼表和泪液分泌的作用具有剂量依赖性。
局部应用TSG-6在炎症介导的干眼中与环孢素滴眼液效果相当。局部应用泼尼松龙可抑制炎症，但会诱导角膜上皮细胞凋亡。
