Autoimmune aspects in glaucoma

Hohenstein-Blaul, Nadine von Thun und; Bell, Katharina; Pfeiffer, Norbert; Grus, Franz H.

doi:10.1016/j.ejphar.2016.04.031

Cited by 26 publications

(26 citation statements)

References 90 publications

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“…Although we lack data regarding the etiology of hypothyroidism, it has previously been shown that hypothyroidism due to autoimmune thyroiditis accounts for more than 80% of all hypothyroid cases[ 1 ]. This is important to acknowledge, as also glaucoma etiologically includes aspects of autoimmunity[ 14 , 15 ]. However, despite the fact that autoimmune diseases tend to co-exist[ 25 ] our data cannot support a significant association between autoimmune thyroiditis and glaucoma.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis has been supported by the finding of a lowering of the intraocular pressure after restoration of euthyroidism following thyroid hormone therapy[ 13 ]. In addition, an interrelationship between hypothyroidism and glaucoma due to a shared autoimmune background has also been suggested but is at present unclarified[ 14 , 15 ]. However, as pointed out in our recent systematic review[ 9 ], the interpretation of the studies dealing with the relationship between hypothyroidism and glaucoma is hampered by methodological shortcomings such as major differences in the sample size, definition of disease phenotypes, lack of appropriate control for co-morbidity and, importantly, focus on the direction of such a potential association.…”

Section: Introductionmentioning

confidence: 99%

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No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

2018

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BackgroundAn interrelationship between hypothyroidism and glaucoma, due to a shared autoimmune background or based on deposition of mucopolysaccharides in the trabecular meshwork in the eye, has been suggested but is at present unsubstantiated. Therefore, our objective was to investigate, at a nationwide and population-based level, whether there is such an association.Subjects and methodsObservational cohort study using record-linkage data from nationwide Danish health registers. 121,799 individuals diagnosed with a first episode of hypothyroidism were identified and were matched with 4 non-hypothyroid controls according to age and sex. Prevalence of glaucoma was recorded and cases and controls were followed over a mean of 7.1 years (range 0–17). Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of hypothyroidism, respectively.ResultsOverall, we found a higher prevalence of glaucoma in subjects with hypothyroidism as compared to controls (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence interval (CI): 1.04–1.13]. Based on the Cox regression model, there was no increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio (HR) 1.00; 95% CI: 0.96–1.06], and the HR decreased further after adjusting for pre-existing co-morbidity (0.88; 95% CI: 0.84–0.93).ConclusionsThere was an increased risk of glaucoma before but not after the diagnosis of hypothyroidism, suggesting that screening for glaucoma in hypothyroid individuals is unwarranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

2018

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“…Glaucoma is a multi-factorial disease and its pathogenesis mechanism is not completely understood. Several mechanisms have been proposed that may contribute to neurodegeneration in glaucoma, such as mitochondrial dysfunction, oxidative stress, secretion of toxic molecules by glial cells, and autoimmunity ( 7 , 64 , 100 , 101 ). Alterations in the level of autoreactive antibodies was first reported two decades back, when it was shown that HSP60 antibody level was increased in the serum of glaucoma patients ( 102 ).…”

Section: Autoimmunity and Glaucomamentioning

confidence: 99%

“…Alterations in the level of autoreactive antibodies was first reported two decades back, when it was shown that HSP60 antibody level was increased in the serum of glaucoma patients ( 102 ). Since then increase or decrease in the level of antibodies against various proteins such as HSP70, HSP27, crytallins, neuron-specific enolase, GST, αFodrin, GFAP, MBP, etc., from sera of NTG as well as POAG patients, has been reported ( 101 ). Some of these antibodies induce death of primary RGCs in vitro , such as HSP27 and HSP60 antibodies ( 101 , 102 ).…”

Section: Autoimmunity and Glaucomamentioning

confidence: 99%

“…Since then increase or decrease in the level of antibodies against various proteins such as HSP70, HSP27, crytallins, neuron-specific enolase, GST, αFodrin, GFAP, MBP, etc., from sera of NTG as well as POAG patients, has been reported ( 101 ). Some of these antibodies induce death of primary RGCs in vitro , such as HSP27 and HSP60 antibodies ( 101 , 102 ). On the other hand, antibodies against some of the proteins, like GFAP, enhance RGC survival and are present at lower level in glaucoma patients ( 103 ).…”

Section: Autoimmunity and Glaucomamentioning

confidence: 99%

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Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin

Swarup

Sayyad

2018

Front. Immunol.

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Optineurin (OPTN) is an adaptor protein that is involved in mediating a variety of cellular processes such as signaling, vesicle trafficking, and autophagy. Certain mutations in OPTN (gene OPTN) are associated with primary open angle glaucoma, a leading cause of irreversible blindness, and amyotrophic lateral sclerosis, a fatal motor neuron disease. Glaucoma-associated mutations of OPTN are mostly missense mutations. OPTN mediates its functions by interacting with various proteins and altered interactions of OPTN mutants with various proteins primarily contribute to functional defects. It interacts with Rab8, myosin VI, Huntigtin, TBC1D17, and transferrin receptor to mediate various membrane vesicle trafficking pathways. It is an autophagy receptor that mediates cargo-selective as well as non-selective autophagy. Glaucoma-associated mutants of OPTN, E50K, and M98K, cause defective vesicle trafficking, autophagy, and signaling that contribute to death of retinal ganglion cells (RGCs). Transgenic mice expressing E50K-OPTN show loss of RGCs and persistent reactive gliosis. TBK1 protein kinase, which mediates E50K-OPTN and M98K-OPTN induced cell death, is emerging as a potential drug target. Autoimmunity has been implicated in glaucoma but involvement of OPTN or its mutants in autoimmnity has not been explored. In this review, we highlight the main functions of OPTN and how glaucoma-associated mutants alter these functions. We also discuss some of the controversies, such as the role of OPTN in signaling to transcription factor NF-κB, interferon signaling, and use of RGC-5 cell line as a cell culture model.

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Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus

Liu,

You,

Zeng

et al. 2024

iMetaOmics

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Glaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that the risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, the mechanism underlying this association remains unclear. Therefore, this study aimed to identify novel common biomarkers and potential therapeutic drugs for SLE and glaucoma. GSE27276, GSE50772, and GSE148371 datasets were sourced from the gene expression omnibus (GEO) database. An integrated analysis of the datasets for both diseases identified biomarkers and thoroughly examined their biological roles and molecular mechanisms using differential expression analysis (DEA), weighted gene co‐expression network analysis (WGCNA), gene enrichment analysis, machine learning, microRNA (miRNA) and transcription factor analyses, immune infiltration analyses, and single‐cell transcriptome analysis. Concurrently, molecular docking was used to forecast potential drugs targeting these biomarkers. Finally, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR) was performed in human trabecular meshwork stem cells to validate the five identified biomarkers. The 10 key genes identified through DEA and WGCNA were predominantly involved in immune, inflammatory, and autophagy pathways. Additionally, machine learning identified five biomarkers, and we established associated transcription factors and miRNA regulatory networks. Immune infiltration analysis indicated an elevated presence of immune cells, including macrophages, T cells, and B cells, in both conditions. Furthermore, the DSigDB database yielded 10 potential therapeutic agents, three of which showed strong binding potential to the biomarkers via molecular docking. The RT‐qPCR results confirmed the trend in gene expression. This study uncovered a new link between SLE and primary open‐angle glaucoma, identifying biomarkers and mechanisms of immunopathogenesis for future research and treatment strategies.

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Autoimmune aspects in glaucoma

Cited by 26 publications

References 90 publications

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin

Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus

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