{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:07:22Z","timestamp":1778857642034,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,1,22]],"date-time":"2017-01-22T00:00:00Z","timestamp":1485043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Shanghai Municipal Health Planning Commission","award":["2015400073"],"award-info":[{"award-number":["2015400073"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1\u2010phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrops was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of non\u2010obese diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrops. Inbred 10\u2010week\u2010old BALB\/c mice were randomly divided into four groups, fingolimod\u2010treated groups at three different concentrations (0.01%, 0.1% and 0.5%) and a negative control group without intervention. Our results showed that in the 0.5% fingolimod group, adverse effects such as photophobia, catacleisis and corneal oedema were observed after 1 week of treatment. 1 month later, corneal opacity, oedema and neovascularization persisted till the mice were killed 2 months later. In contrast, there was no significant abnormality in the negative control group, and 0.01% and 0.1% fingolimod\u2010treated groups. During a 2\u2010month treatment period, we did not detect fingolimod, nor significant change in blood cells in peripheral blood, nor pathological changes in retina and systemic organs. Combined with our previous study and the current results, we recommend that an optimal range of safe and effective concentration of fingolimod as eyedrops is between 0.005% and 0.1%.<\/jats:p>","DOI":"10.1111\/bcpt.12717","type":"journal-article","created":{"date-parts":[[2016,11,26]],"date-time":"2016-11-26T09:09:13Z","timestamp":1480151353000},"page":"398-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Adverse Effect Profile of Topical Ocular Administration of Fingolimod for Treatment of Dry Eye Disease"],"prefix":"10.1111","volume":"120","author":[{"given":"Weibao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Huashan Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Huashan Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Huashan Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Huashan Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-0124(12)70085-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3181ca327e"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153573"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2015.12.004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2015.11.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(00)00035-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.3.330"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)00176-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.47.208"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00451.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070238"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7115-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-015-0224-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.12.040"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.06.032"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-0124(12)70120-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0910fje"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000077"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.400"},{"key":"e_1_2_7_22_1","first-page":"243","article-title":"The multiple sclerosis drug fingolimod (FTY720) stimulates neuronal gene expression, axonal growth and regeneration","volume":"279","author":"Anastasiadou S","year":"2016","journal-title":"ExpNeurol"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-783"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401842"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4769"},{"key":"e_1_2_7_26_1","first-page":"624","article-title":"Topical application of FTY720 and cyclosporin A prolong corneal graft survival in mice","volume":"18","author":"Liu Y","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052643"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141781"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2014.05.005"}],"container-title":["Basic &amp; 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