2. Academic Validation
  3. Involvement of aberrant acinar cell proliferation in scopolamine-induced dry eye mice

Involvement of aberrant acinar cell proliferation in scopolamine-induced dry eye mice

  • Exp Eye Res. 2023 Jan 22;227:109391. doi: 10.1016/j.exer.2023.109391.
Qing Chen 1,  Mingli Qu 2,  Bin Zhang 2,  Sai Zhang 3,  Xia Qi 2,  Yujie Qiao 3,  Qingjun Zhou 4
Affiliations

Affiliations

  • 1 School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, 261053, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, Shandong, 266071, China.
  • 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, Shandong, 266071, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, 266071, China.
  • 3 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, Shandong, 266071, China.
  • 4 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, Shandong, 266071, China; Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, 266071, China. Electronic address: qjzhou2000@hotmail.com.
PMID: 36696946 DOI: 10.1016/j.exer.2023.109391
Abstract

Dry eye is a multifactorial disease that causes dryness, inflammation and damage of ocular surface. Subcutaneous injection of the muscarinic cholinergic antagonist scopolamine under desiccating stress reduces tear production and induces dry eye symptoms in mice. However, the expression profile and pathogenic changes of the lacrimal gland remain incompletely understood. In the present study, we performed comparative transcriptomic analysis of lacrimal glands from the control and scopolamine-treated mice. Primary analysis identified 677 upregulated genes and 269 downregulated genes in the lacrimal gland of mice with scopolamine treatment. Unexpectedly, KEGG pathway and hierarchical clustering analysis showed the enrichment of "DNA replication" and "cell cycle" categories in the upregulated genes. Subsequently, we confirmed that the acinar cells were the major proliferating cells of lacrimal gland, which exhibited significant increasing of the proliferating cell nuclear antigen (PCNA) expression after scopolamine treatment, accompanied with the upregulation of DNA damage marker γ-H2AX. More importantly, both prophylactic and therapeutic administration of the cyclin-dependent kinase (CDK) inhibitor AT7519 rescued the tear reduction and alleviated dry eye severity in the scopolamine-treated mice, including corneal epithelial barrier function, lacrimal and corneal inflammation, and conjunctival goblet cell density. Therefore, we conclude that aberrant acinar cell proliferation is involved in the scopolamine-induced tear reduction and dry eye onset, which can be improved by AT7519 treatment.

Keywords

Acinar cells; CDK inhibitor; Dry eye; Lacrimal gland; PCNA.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z