Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.

Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.
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DOI:
10.1007/s40123-023-00656-6
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发表时间:
2023-04
影响因子:
3.3
通讯作者:
Figueiredo, Francisco C.
Figueiredo, Francisco C.
中科院分区:
医学3区
文献类型:
--
作者:
Figueiredo, Gustavo S.;Hogg, Jeffry;Okonkwo, Arthur;Baylis, Oliver J.;Berry, Monica;Ali, Simi;Lako, Majlinda;Figueiredo, Francisco C.

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我们的目的是确定炎症细胞因子在自体培养的角膜缘上皮干细胞移植(CLET)之前和之后的化学烧伤引起的单侧角膜缘干细胞缺乏症(TLSCD)患者的眼泪中的表达。在CLET前后的固定时间点,从23名单侧TLSCD患者和11名健康对照者的双眼收集泪液样本。使用标准化方法从Schirmer条提取溶解的分子,并在十种炎性细胞因子的阵列板(V-FXR Proinflammatory Panel 1 Human Kit,MSD)上进行分析。与基线时未受影响的眼睛相比,TLSCD眼睛中的IL 1 β表达显著升高(p < 0.0001),但在CLET后3个月降至正常(p = 0.22)。IL 6和IL 8在基线时未受影响,但在CLET后1个月在TLSCD眼中显著升高(分别为p = 0.001和p < 0.0001)。IL 6在CLET后3个月恢复正常,IL 8在6个月恢复正常。在CLET后12个月,IL 1 β、IL 6和IL 8表达显著重新增加(分别为p < 0.0001、p = 0.0001和p = 0.0003)。单侧TLSCD患者双眼IFNγ、IL 10和IL 12 p70表达在所有时间点均显著降低。IL 1 β是TLSCD眼中炎症的特异性标志物,其可以在治疗上靶向于CLET前以改善干细胞植入。在CLET后12个月,IL 1 β、IL 6和IL 8水平的峰值与局部类固醇的停止一致,表明正在进行的亚临床炎症。因此,我们建议在有穿透性角膜移植指征的病例中不要停止局部类固醇治疗;然而,需要进一步的调查来确定这一点。欧盟药品监管机构临床试验数据库(EuDRACT 2011-000608-16); ISRCTN(国际标准随机对照试验编号(isrctn 51772481))。
We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer’s strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). IL1β expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1β, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. IL1β is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1β, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011—000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481).
DOI: 10.1155/2016/9672082
发表时间: 2016
影响因子: --
作者:
Micera A;Di Zazzo A;Esposito G;Sgrulletta R;Calder VL;Bonini S
通讯作者: Bonini S
DOI: 10.1016/j.jtos.2017.09.004
发表时间: 2018-01
期刊: The ocular surface
影响因子: --
作者:
Cavalcanti BM;Cruzat A;Sahin A;Pavan-Langston D;Samayoa E;Hamrah P
通讯作者: Hamrah P
DOI: 10.1002/stem.276
发表时间: 2010-03-31
期刊: STEM CELLS
影响因子: 5.2
作者:
Kolli, Sai;Ahmad, Sajjad;Figueiredo, Francisco
通讯作者: Figueiredo, Francisco
DOI: 10.1016/s0161-6420(02)00994-6
发表时间: 2002-05-01
期刊: OPHTHALMOLOGY
影响因子: 13.7
作者:
Samson, CM;Nduaguba, C;Foster, CS
通讯作者: Foster, CS
DOI: 10.1007/s12026-009-8150-5
发表时间: 2010-07
影响因子: 4.4
作者:
Hedrich CM;Bream JH
通讯作者: Bream JH