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Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland.

Authors
  • de Souza, Rodrigo G1
  • Yu, Zhiyuan2
  • Hernandez, Humberto2
  • Trujillo-Vargas, Claudia M3
  • Lee, Andrea4
  • Mauk, Kelsey E4
  • Cai, Jiyang5
  • Alves, Milton R6
  • de Paiva, Cintia S7
  • 1 Department of Ophthalmology, Baylor College of Medicine, Houston, Texas; Department of Ophthalmology, University of São Paulo, São Paulo, Brazil. , (Brazil)
  • 2 Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
  • 3 Department of Ophthalmology, Baylor College of Medicine, Houston, Texas; Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia. , (Colombia)
  • 4 Graduate Program in Immunology and Microbiology, Baylor College of Medicine, Houston, Texas.
  • 5 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
  • 6 Department of Ophthalmology, University of São Paulo, São Paulo, Brazil. , (Brazil)
  • 7 Department of Ophthalmology, Baylor College of Medicine, Houston, Texas; Department of Ophthalmology, University of São Paulo, São Paulo, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Feb 01, 2021
Volume
191
Issue
2
Pages
294–308
Identifiers
DOI: 10.1016/j.ajpath.2020.10.013
PMID: 33159886
Source
Medline
Language
English
License
Unknown

Abstract

Inflammation and oxidative stress accompany aging. This study investigated the interplay between oxidative stress and inflammation in the lacrimal gland. C57BL/6 mice were used at 2 to 3, 12, and 24 months of age. Nuclear factor erythroid derived-2-related factor 2 (Nrf2)-/- and corresponding wild-type mice were used at 2 to 3 and 12 to 13 months of age. A separate group of 15.5 to 17 months of age C57BL/6 mice received a diet containing an Nrf2 inducer (Oltipraz) for 8 weeks. Aged C57BL/6 lacrimal glands showed significantly greater lymphocytic infiltration, higher levels of MHC II, IFN-γ, IL-1β, TNF-α, and cathepsin S (Ctss) mRNA transcripts, and greater nitrotyrosine and 4-hydroxynonenal protein. Young Nrf2-/- mice showed an increase in IL-1β, IFN-γ, MHC II, and Ctss mRNA transcripts compared with young wild-type mice and greater age-related changes at 12 to 13 months of age. Oltipraz diet significantly decreased nitrotyrosine and 4-hydroxynonenal and decreased the expression of IL-1β and TNF-α mRNA transcripts, while decreasing the frequency of CD45+CD4+ cells in lacrimal glands and significantly increasing conjunctival goblet cell density compared with a standard diet. The findings provide novel insight into the development of chronic, low-grade inflammation and oxidative stress in age-related dry eye. New therapies targeting oxidative stress pathways will be valuable in treating age-related dry eye. Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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