Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes.
The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea.
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Fang
F
Song
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Yunxia
Y
Xue
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Dong
D
Dong
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Jun
J
Liu
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Ting
T
Fu
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Chengju
C
Xiao
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Hanqing
H
Wang
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Cuipei
C
Lin
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Peng
P
Liu
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Jiajun
J
Zhong
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Yabing
Y
Yang
Department of Medical Images, The Third People's Hospital, Puyang, China.
Zhaorui
Z
Wang
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Hongwei
H
Pan
International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.
Jiansu
J
Chen
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Yangqiu
Y
Li
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.
Dongqing
D
Cai
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, P.R. China.|International Ocular Surface Research Centre and Institute of Ophthalmology, Jinan University Medical School, Guangzhou 510632, P.R. China.|Section of Leukocyte Biology, Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.
Zhijie
Z
Li
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D013311:Streptozocin
D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin