title: Modulation of Circadian Rhythms Affects Corneal Epithelium Renewal and Repair in Mice.
abstract: In mammalian corneal epithelium, mitosis shows a distinct circadian pattern. However, how this circadian pattern is maintained, and how it or its disruption influence renewal and regeneration remain unclear.
  
  
  
  C57BL/6 mice were maintained under 12-hour light/12-hour dark (LD), 12-hour light/12-hour light (LL), 12-hour dark/12-hour dark (DD), or reversed LD (DL, 12-hour dark/12-hour light; jet-lag defined as a shift of 12 hours) conditions. Mitotic cells in corneal epithelium were enumerated and analyzed via immunofluorescence at different zeitgeber times (ZTs). Expression of core clock genes (Clock, Bmal1, Period2, Cry1, and Rev-erbα) was qualified via quantitative RT-PCR. The rate and quality of healing at different ZT times and after administration of two small-molecule modifiers of the circadian clock, KL001 and SR8278, was evaluated.
  
  
  
  In this study, photic cues were found to influence the 24-hour rhythm of corneal clock gene expression and epithelial cell mitosis in mice. Disruption of the circadian clock by exposure to constant light, constant dark, or jet-lag conditions modified the normal 24-hour patterns of corneal epithelial mitosis and corneal clock gene expression. The time of day of wound occurrence affected the rate and quality of corneal healing, with both of these parameters peaking during the more mitotically active hours of the morning. The two small-molecule modifiers of the circadian clock, KL001 and SR8278, had negative and positive effects on corneal wound healing, respectively.
  
  
  
  Circadian rhythms significantly influence corneal epithelium renewal and repair in mice. Our findings reveal possible opportunities for biological rhythm-based interventional strategies to control corneal healing and restore corneal homeostasis.
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Chengju
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Cuipei
authors.initials: C
authors.lastname: Lin
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China 2Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fu
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Third People's Hospital, Puyang, Henan, China.
authors.forename: Zhaorui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Pan
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China 2Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Jiansu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Jinan University, Guangzhou, China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Cai
authors.affiliation: International Ocular Surface Research Center and Institute of Ophthalmology, Jinan University, Guangzhou, China 2Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China 5Section of Leukocyte Biology, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002940:Circadian Rhythm; D065306:Corneal Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000235:genetics*; D017440:Photoperiod; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D056926:CLOCK Proteins