TNF is a critical cytokine in age-related dry eye disease.

Aug 28, 2023

Experts: Yashaswini Kelagere,Kaitlin K Scholand,Erica N DeJong,Andrea I Boyd,Zhiyuan Yu,Roger A Astley,Michelle C Callegan,Dawn Me Bowdish,Helen P Makarenkova,Cintia S de Paiva

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), IFN-γ, IL-12p40, IL-17, and IL-10 proteins in tears of aged mice. Moreover, genetic loss of the Tnf in mice decreased goblet cell loss and the development of ectopic lymphoid structures in the lacrimal gland compared to wild-type mice. This was accompanied by a decrease in cytokine production. Treatment of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease.
Copyright © 2023. Published by Elsevier Inc.

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ABOUT THE EXPERTS

Yashaswini Kelagere,Kaitlin K Scholand,Erica N DeJong,Andrea I Boyd,Zhiyuan Yu,Roger A Astley,Michelle C Callegan,Dawn Me Bowdish,Helen P Makarenkova,Cintia S de Paiva

Yashaswini Kelagere

Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA. Electronic address: yashaswinikelagere@gmail.com.

Kaitlin K Scholand

Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; Biochemistry and Cell Biology Graduate Program, Department of BioSciences, Rice University, Houston, TX, USA. Electronic address: Kaitlin.Scholand@bcm.edu.

Erica N DeJong

McMaster Immunology Research Centre, McMaster University, Ontario, Canada. Electronic address: dejone1@mcmaster.ca.

Andrea I Boyd

Graduate Program in Immunology & Microbiology, Baylor College of Medicine, USA. Electronic address: Andrea.Lee@bcm.edu.

Zhiyuan Yu

Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA. Electronic address: zhiyuan.yu@bcm.edu.

Roger A Astley

Departments of Ophthalmology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Roger-Astley@ouhsc.edu.

Michelle C Callegan

Departments of Ophthalmology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Michelle-Callegan@ouhsc.edu.

Dawn Me Bowdish

McMaster Immunology Research Centre, McMaster University, Ontario, Canada. Electronic address: bowdish@mcmaster.ca.

Helen P Makarenkova

Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. Electronic address: hmakarenk@scripps.edu.

Cintia S de Paiva

Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; Biochemistry and Cell Biology Graduate Program, Department of BioSciences, Rice University, Houston, TX, USA. Electronic address: cintiadp@bcm.edu.