Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland

Souza, Rodrigo G. de; Yu, Zhiyuan; Hernandez, Humberto; Trujillo-Vargas, Claudia M.; Lee, Andrea; Mauk, Kelsey E.; Cai, Jiyang; Alves, Mílton Ruiz; Paiva, Cintia S. de

doi:10.1016/j.ajpath.2020.10.013

Cited by 37 publications

(25 citation statements)

References 95 publications

(88 reference statements)

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“…When Oltipraz, an NRF2 inducer, was administered to aged mice, oxidative stress markers such as nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were decreased in the lacrimal gland. Concomitantly, infiltration of immune cells into the lacrimal gland was also decreased, which was accompanied by a significant increase in conjunctival goblet cell density compared to aged mice fed a standard diet [ 99 ].…”

Section: Tissue Aging and The Keap1-nrf2 Systemmentioning

confidence: 99%

The KEAP1-NRF2 System in Healthy Aging and Longevity

Matsumaru

Motohashi

2021

Antioxidants

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Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the quality and quantity of the stresses generate diverse impacts on the organismal aging process. In the current oxygenic atmosphere on earth, oxidative stress caused by reactive oxygen species is one of the most common and critical environmental factors for life. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (KEAP1-NRF2) system is a critical defense mechanism of cells and organisms in response to redox perturbations. In the presence of oxidative and electrophilic insults, the thiol moieties of cysteine in KEAP1 are modified, and consequently NRF2 activates its target genes for detoxification and cytoprotection. A number of studies have clarified the contributions of the KEAP1-NRF2 system to the prevention and attenuation of physiological aging and aging-related diseases. Accumulating knowledge to control stress-induced damage may provide a clue for extending healthspan and treating aging-related diseases. In this review, we focus on the relationships between oxidative stress and aging-related alterations in the sensory, glandular, muscular, and central nervous systems and the roles of the KEAP1-NRF2 system in aging processes.

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Section: Tissue Aging and The Keap1-nrf2 Systemmentioning

confidence: 99%

The KEAP1-NRF2 System in Healthy Aging and Longevity

Matsumaru

Motohashi

2021

Antioxidants

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“…Studies of conjunctival tolerance in Sjögren's syndrome‐like mice are lacking in the literature. Aged lacrimal glands also display lymphocytic infiltration [147,148,158]. All the aforementioned mechanisms at work in the aged ocular surface have been linked to decreased or altered Treg generation and impaired mucosal tolerance induction in other tissues [25,123,124,159–161].…”

Section: Conjunctival Tolerance and Ageingmentioning

confidence: 99%

Age‐related changes in ocular mucosal tolerance: Lessons learned from gut and respiratory tract immunity

Galletti

Paiva

2021

Immunology

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Summary The ocular surface is the part of the visual system directly exposed to the environment, and it comprises the cornea, the first refractive tissue layer and its surrounding structures. The ocular surface has evolved to keep the cornea smooth and wet, a prerequisite for proper sight, and also protected. To this aim, the ocular surface is a bona fide mucosal niche with an immune system capable of fighting against dangerous pathogens. However, due to the potential harmful effects of uncontrolled inflammation, the ocular surface has several mechanisms to keep the immune response in check. Specifically, the ocular surface is maintained inflammation‐free and functional by a particular form of peripheral tolerance known as mucosal tolerance, markedly different from the immune privilege of intraocular structures. Remarkably, conjunctival tolerance is akin to the oral and respiratory tolerance mechanisms found in the gut and airways, respectively. And also similarly, this form of immunoregulation in the eye is affected by ageing just as it is in the digestive and respiratory tracts. With ageing comes an increased prevalence of immune‐based ocular surface disorders, which could be related to an age‐related impairment of conjunctival tolerance. The purpose of this review was to summarize the present knowledge of ocular mucosal tolerance and how it is affected by the ageing process in the light of the current literature on mucosal immunoregulation of the gut and airways.

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“…In the normal lacrimal gland, there were very few inflammatory cells. 21 PMN staining showed sporadic polymorphonuclear leukocytes in the normal rat lacrimal gland but increased from day one of lacrimal duct ligation and reached peak at day seven. The PMN-positive cells slightly decreased after 14 days ( Figs.…”

Section: Resultsmentioning

confidence: 92%

Lacrimal Gland Microenvironment Changes After Obstruction of Lacrimal Gland Ducts

Sun

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate microenvironment changes of the lacrimal gland after obstruction of lacrimal gland ducts. Methods The ducts of rat exorbital lacrimal gland were ligated by sutures for different durations. After that, the sutures in some animals were released, and they were observed for 21 days to evaluate the recovery of the lacrimal gland. Slit lamp and tear secretion test was performed to evaluate ocular surface and lacrimal gland function. The lacrimal gland and cornea were harvested and processed for hematoxylin and eosin staining, oil red O staining, LipidTOX staining, Masson staining, quantitative real time polymerase chain reaction, and immunofluorescence staining. Results After the lacrimal gland ducts were blocked, tear secretion and the weight of the lacrimal gland were reduced. Incidence of corneal neovascularization increased after seven days. Intraglandular ducts dilated and acini destroyed. Long-term ligation induced fibrosis and lipid accumulation of the lacrimal glands. Inflammatory cell infiltrated and inflammatory factors upregulated. Proliferative and apoptotic cells increased. Structure of myoepithelial cells and basement membrane was destroyed. The p63 expression increased whereas Pax6 expression decreased. After suture release, tear secretion and structure of acini could recover in less than seven days after ligation, with a decrease in inflammatory cell infiltration and fibrosis relief. Apoptotic cells and proliferative cells increased at five days thereafter. The structure of the myoepithelial cells and basement membrane could not recover three days after ligation, and the number of mesenchymal cells increased in ligation after five to 14 days. Conclusions Blockage of the lacrimal gland ducts results in dystrophy of lacrimal gland acini cells, inflammation, and lipid accumulation of the lacrimal gland microenvironment. Long-term duct blockage will cause irreversible lacrimal gland failure.

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Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland

Cited by 37 publications

References 95 publications

The KEAP1-NRF2 System in Healthy Aging and Longevity

The KEAP1-NRF2 System in Healthy Aging and Longevity

Age‐related changes in ocular mucosal tolerance: Lessons learned from gut and respiratory tract immunity

Lacrimal Gland Microenvironment Changes After Obstruction of Lacrimal Gland Ducts

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