Oxidative Stress in the Protection and Injury of the Lacrimal Gland and the Ocular Surface: are There Perspectives for Therapeutics?

Lemos, Camila Nunes; Silva, Lilian Eslaine Costa Mendes da; Faustino, Jacqueline; Fantucci, Marina Zílio; Murashima, Adriana de Andrade Batista; Adriano, Leidiane; Alves, Mônica; Rocha, Eduardo Melani

doi:10.3389/fcell.2022.824726

Cited by 5 publications

(6 citation statements)

References 170 publications

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“…61 The C0 cell subtype predominantly releases LPO and the cytokine epidermal growth factor (EGF), both of which are linked to the antibacterial and defensive roles of the ocular surface. 62,63 Meanwhile, the Car6 protein produced by the C1 subtype is involved in maintaining the pH homeostasis of tears. 12,32 These findings indicate that these two kinds of acinar cells probably work together to regulate the makeup of the tear fluid.…”

Section: Discussionmentioning

confidence: 99%

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease

Tang,

Dou,

Wei

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively characterize LG cellular heterogeneity under normal and DED conditions using single-nucleus RNA sequencing (snRNA-seq). METHODS. SingleLG nuclei isolated from mice with or without DED induced by scopolamine (SCOP)/desiccating stress (DS) were subjected to snRNA-seq using the 10x Genomics platform. These cells were clustered and annotated using the t-distributed stochastic neighbor embedding (t-SNE) method and unbiased computational informatic analysis. Cluster identification and functional analysis were performed based on marker gene expression and bioinformatic data mining. RESULTS.The snRNA-seq analysis of 30,351 nuclei identified eight major cell types, with acinar cells (∼72.6%) being the most abundant cell type in the LG. Subclustering analysis revealed that the LG mainly contained two acinar cell subtypes, two ductal cell subclusters, three myoepithelial cell (MECs) subtypes, and four immunocyte subclusters. In the SCOP-induced DED model, three major LG parenchymal cell types were significantly altered, characterized by a reduced proportion of acinar cells with a lowered secretion potential and an augmented proportion of ductal cells and MECs. LG immunocytes in DED scenarios showed an intensified inflammatory response and dysregulated intercellular communication with three major LG parenchymal cells. CONCLUSIONS. Overall, this study offers a systemic single-nucleus transcriptomic profile ofLGs in both normal and DED conditions and an atlas of the complicated interactions of immunocytes with major LG parenchymal cells. The findings also facilitate understanding the pathogenesis of DED.

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Section: Discussionmentioning

confidence: 99%

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease

Tang,

Dou,

Wei

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…Antioxidant enzymes on the OS provide sophisticated protection to the eye against oxidative stress (50) (51). Reactive oxygen species (ROS) products have important roles in homeostasis and cell signaling, yet an imbalance of ROS production or scavenging causes oxidative damage that results in cell damage and death (52) (53). The OS tissues, such as the cornea, possess protective mechanisms against endogenous oxidative stress (54).…”

Section: Discussionmentioning

confidence: 99%

Profiling Tear Film Enzymes Reveals Major Metabolic Pathways Involved in the Homeostasis of the Ocular Surface

Arslan

Brignole‐Baudouin

Baudouin

et al. 2022

Preprint

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Background The role of ocular surface enzymes is of great interest. Therefore, this study first aimed to profile and classify enzymes identified on the ocular surface to describe major biological processes and pathways that are involved in the maintenance of homeostasis. Secondly, we aimed to compare the enzymatic profiles between two main tear collection methods, capillary tubes (CT) and Schirmer strips (ScS). Methods A comprehensive tear proteomic dataset was generated by pooling all identified enzymes from nine tear proteomic analyses of healthy subjects using mass spectrometry. In these studies, tear fluid was collected using CT (n = 4), ScS (n = 4) or both collection methods (n = 1). The classification and functional analysis of enzymes was performed using a combination of bioinformatic tools. Results The generated dataset enabled the identification of 1010 enzymes. The most representative classes were hydrolases (EC 3) and transferases (EC 2). Phosphotransferases, esterases and peptidases were the most represented subclasses. A large part of identified enzymes was common to both collection methods (n = 499). More enzymes were specifically detected in the ScS-extracted proteome. The immune system and metabolism of proteins, carbohydrates and lipids formed the major pathways of the identified enzymes. Metabolic processes of nucleosides, cellular amid, sugar and sulfur compounds constituted the most enriched biological processes. Conclusions Knowledge about these highly druggable molecules could help to predict the metabolism of ophthalmic drugs, and develop novel prodrug strategies as well as new drug delivery systems. Combining extensive knowledge about ocular surface enzymes with new approaches and techniques might open up new avenues for ocular drug metabolisms.

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“…Such accumulation leads to damage of cellular components, including proteins, lipids, and DNA, causing cell inflammation and apoptosis 2 . This, in turn, can contribute to organismal aging and physical dysfunction, ultimately resulting in a series of age‐related eye diseases 3,4 . At the same time, aging itself also increases oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

“… 2 This, in turn, can contribute to organismal aging and physical dysfunction, ultimately resulting in a series of age‐related eye diseases. 3 , 4 At the same time, aging itself also increases oxidative stress. On the one hand, endogenous antioxidants decrease with increasing age, accompanied by excessive radical and lipid peroxide generation.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant potential of chlorogenic acid in Age‐Related eye diseases

Tang,

Fang,

Shi

et al. 2024

Pharmacology Res & Perspec

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Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue‐light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age‐related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti‐inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age‐related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.

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Oxidative Stress in the Protection and Injury of the Lacrimal Gland and the Ocular Surface: are There Perspectives for Therapeutics?

Cited by 5 publications

References 170 publications

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease

Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease

Profiling Tear Film Enzymes Reveals Major Metabolic Pathways Involved in the Homeostasis of the Ocular Surface

Antioxidant potential of chlorogenic acid in Age‐Related eye diseases

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