Rapamycin Eyedrops Increased CD4+Foxp3+ Cells and Prevented Goblet Cell Loss in the Aged Ocular Surface

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.

• Autores: Trujillo Vargas, Claudia Milena; Kutlehria, Shallu; Hernández, Humberto; de Souza, Rodrigo G; Lee, Andrea; Yu, Zhiyuan; Pflugfelder, Stephen C; Singh, Mandip; de Paiva, Cintia S
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40525
• Acceso en línea: https://hdl.handle.net/10495/40525
• Palabra clave: Aging; Envejecimiento; Autophagy-Related Protein-1 Homolog; Homólogo de la Proteína 1 Relacionada con la Autofagia; CD4 Antigens; Antígenos CD4; Cell Lineage; Linaje de la Célula; Conjunctiva; Conjuntiva; Cornea; Córnea; Disease Models, Animal; Modelos Animales de Enfermedad; Dry Eye Syndromes; Síndromes de Ojo Seco; Forkhead Transcription Factors; Factores de Transcripción Forkhead; Goblet Cells; Células Caliciformes; Inflammation; Inflamación; Interferon-gamma; Interferón gamma; Leukocyte Common Antigens; Antígenos Comunes de Leucocito; Ophthalmic Solutions; Soluciones Oftálmicas; Sirolimus; Sirolimus; Vascular Endothelial Growth Factor A; Factor A de Crecimiento Endotelial Vascular; https://id.nlm.nih.gov/mesh/D000375; https://id.nlm.nih.gov/mesh/D000071189; https://id.nlm.nih.gov/mesh/D015704; https://id.nlm.nih.gov/mesh/D019070; https://id.nlm.nih.gov/mesh/D003228; https://id.nlm.nih.gov/mesh/D003315; https://id.nlm.nih.gov/mesh/D004195; https://id.nlm.nih.gov/mesh/D015352; https://id.nlm.nih.gov/mesh/D051858; https://id.nlm.nih.gov/mesh/D020397; https://id.nlm.nih.gov/mesh/D007249; https://id.nlm.nih.gov/mesh/D007371; https://id.nlm.nih.gov/mesh/D017493; https://id.nlm.nih.gov/mesh/D009883; https://id.nlm.nih.gov/mesh/D020123; https://id.nlm.nih.gov/mesh/D042461
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/