PMID- 34118276 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20211130 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 209 DP - 2021 Aug TI - Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics. PG - 108665 LID - S0014-4835(21)00231-1 [pii] LID - 10.1016/j.exer.2021.108665 [doi] AB - PURPOSE: To investigate the effect of age on wound healing after small incision lenticule extraction (SMILE) and the underlying metabolomic mechanisms. METHODS: This prospective study was conducted on 216 patients in four groups: the 18-20 (n = 38, Group I), 21-30 (n = 84, Group Ⅱ), 31-40 (n = 58, Group Ⅲ), and 41-50 (n = 36, Group IV) age groups. The density of corneal epithelial wing cells, basal cells, corneal stromal cells, endothelial cells and corneal nerves were examined with a laser confocal microscope (HRT III-RCM) before and 1 month, 3 month, 6 month and 1 year after SMILE. The central nerve fiber length (CNFL), the central corneal nerve fibre density (CNFD), and the central corneal nerve branch density (CNBD) were analyzed by Nero J. The corneal stroma lenticules were obtained from SMILE to analyze metabolites by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). RESULTS: The density of corneal wing epithelial cells and basal epithelial cells have no significant difference among the four groups. The CNFL was 21.90 +/- 1.68 mm/mm(2) in Group Ⅰ and 21.63 +/- 2.09 mm/mm(2) in Group Ⅱ after 1 year of SMILE, which represented a return to the preoperative level, whereas the CNFL of Group Ⅲ (19.40 +/- 0.98 mm/mm(2)) and Group Ⅳ (18.94 +/- 0.72 mm/mm(2)) were lower than that preoperation (P <0.01). CNFL repair had a negative correlation with age after surgery (Pearson's R = -0.572, P <0.01). The CNFD and the CNBD showed the same trend with the CNFL (Pearson's R = -0.602 and -0.531, P <0.05). Through screening the significantly different metabolites between the 18-30 age group (including Group I and Group Ⅱ) and other two groups, 6 common remarkably different metabolites were identified. Meanwhile, 5 unique different metabolites were identified only between the 18-30 age group and the 31-40 age group. Six unique different metabolites were identified only between the 18-30 age group and the 41-50 age group. CONCLUSION: Corneal nerve repair after SMILE was significantly affected by age. The identified age-associated differences in metabolites were mainly related to inflammation, oxidation, nerve protection and regeneration. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Li, Min AU - Li M AD - Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: rgswan@163.com. FAU - Liu, Lin AU - Liu L AD - Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. FAU - Shi, Yuehui AU - Shi Y AD - Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. FAU - Sun, Lina AU - Sun L AD - Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. FAU - Ma, Xiaoyun AU - Ma X AD - Department of Ophthalmology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China. Electronic address: maxiaoy1820@126.com. FAU - Zou, Jun AU - Zou J AD - Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: zoujun70@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210610 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 SB - IM MH - Adolescent MH - Adult MH - Cornea/*innervation/metabolism/pathology MH - Follow-Up Studies MH - Humans MH - *Keratomileusis, Laser In Situ MH - Lasers, Excimer/*therapeutic use MH - Male MH - Metabolomics/*methods MH - Microscopy, Confocal MH - Middle Aged MH - Myopia/diagnosis/metabolism/*surgery MH - Nerve Fibers/*physiology MH - Nerve Regeneration/*physiology MH - Prospective Studies MH - Time Factors MH - Young Adult OTO - NOTNLM OT - Age OT - Corneal wound healing OT - Metabolite OT - Small incision lenticule extraction (SMILE) EDAT- 2021/06/13 06:00 MHDA- 2021/12/01 06:00 CRDT- 2021/06/12 20:08 PHST- 2021/01/06 00:00 [received] PHST- 2021/06/01 00:00 [revised] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/06/13 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2021/06/12 20:08 [entrez] AID - S0014-4835(21)00231-1 [pii] AID - 10.1016/j.exer.2021.108665 [doi] PST - ppublish SO - Exp Eye Res. 2021 Aug;209:108665. doi: 10.1016/j.exer.2021.108665. Epub 2021 Jun 10.