Glaucoma – risk factors and current challenges in the diagnosis of a leading cause of visual impairment

Lee, Samantha Sze‐Yee; Mackey, David A.

doi:10.1016/j.maturitas.2022.05.002

Cited by 39 publications

(18 citation statements)

References 115 publications

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“…Exposure to certain wavelengths or intensities of light for a certain time can result in serious damage to the retina [14][15] , which may facilitate the development of age-related ocular disorders. Other risk factors [16] , including thin corneas, positive family history, and ethnicity, are also connected with the pathogenesis of glaucoma. Currently, IOP is the sole variable that can be controlled and is proven to be effective in glaucoma treatment [17] .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction in glaucomatous degeneration

Zhang¹,

Chen²,

Zhang³

2023

Int J Ophthalmol

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Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death of retinal ganglion cells (RGCs), atrophy of the optic nerve, and loss of visual ability. The main risk factors for glaucoma consist of the pathological elevation of intraocular pressure (IOP) and aging. Although the mechanism of glaucoma remains an open question, a theory related to mitochondrial dysfunction has been emerging in the last decade. Reactive oxygen species (ROS) from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction. Oxidative stress takes place when the cellular antioxidant system fails to remove excessive ROS promptly. Meanwhile, more and more studies show that there are other common features of mitochondrial dysfunction in glaucoma, including damage of mitochondrial DNA (mtDNA), defective mitochondrial quality control, ATP reduction, and other cellular changes, which are worth summarizing and further exploring. The purpose of this review is to explore mitochondrial dysfunction in the mechanism of glaucomatous optic neuropathy. Based on the mechanism, the existing therapeutic options are summarized, including medications, gene therapy, and red-light therapy, which are promising to provide feasible neuroprotective ideas for the treatment of glaucoma.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction in glaucomatous degeneration

Zhang¹,

Chen²,

Zhang³

2023

Int J Ophthalmol

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“…Early monitoring and diagnosis based on genotype, combined with early intervention, could be transformative for precision clinical care of glaucoma ( Lee and Mackey, 2022 ). Glaucoma is a heterogeneous disease, and genetic risk for glaucoma is complex and extends well beyond myocilin, but patients with the highest combination of known genetic risk variants are diagnosed on average 5 years earlier than those with fewer genetic risk variants ( Fan et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Quantitative differentiation of benign and misfolded glaucoma-causing myocilin variants on the basis of protein thermal stability

Scelsi

Hill

Barlow

et al. 2023

Disease Models &Amp; Mechanisms

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Accurate predictions of pathogenicity for mutations associated with genetic disease are key to the success of precision medicine. Inherited, missense coding mutations in the myocilin gene (MYOC), within its olfactomedin (OLF) domain, comprise the strongest genetic link to primary open angle glaucoma via a toxic gain of function, and MYOC is an attractive precision medicine target. However, not all mutations in MYOC cause glaucoma, and common variants are expected to be neutral polymorphisms. The gnomAD database lists ∼100 missense variants documented within OLF, all of which are relatively rare (allele frequency <0.001%) and nearly all are of unknown pathogenicity. To disambiguate disease from benign OLF variants, we first characterized the most prevalent population-based variants using a suite of cellular and biophysical assays, and identify two variants with features of aggregation-prone familial disease variants. Next, we consider all available biochemical and clinical data to demonstrate that pathogenic and benign variants can be differentiated statistically based on a single metric, thermal stability of OLF. Our results motivate genotyping MYOC in patients for clinical monitoring of this widespread, painless, and irreversible age-onset disease.

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“…The slow degeneration of retinal ganglion cells (RGCs) and their axons is its characteristic (Fernández-Albarral et al 2021). Elevated intraocular pressure (IOP) is a persistent trait caused by a complex, largely unidentified set of genetic and environmental causes, and it is a major risk factor for glaucoma (Lee and Mackey 2022). RGC apoptosis in a rat model of glaucoma can be seen for the first time after two weeks, and it is consistent with decreased RGC numbers, indicating that apoptosis may be the main factor in decreased RGC numbers (Chen et al 2011).…”

Section: Glaucomamentioning

confidence: 99%

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases

Nasrolahi,

Khojasteh Pour,

Mousavi Salehi

et al. 2023

J. Cell Commun. Signal.

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Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that are longer than 200 nucleotides in length. LncRNAs are implicated in gene expression at the transcriptional, translational, and epigenetic levels, and thereby impact different cellular processes including cell proliferation, migration, apoptosis, angiogenesis, and immune response. In recent years, numerous studies have demonstrated the significant contribution of lncRNAs to the pathogenesis and progression of various diseases, such as stroke, heart disease, and cancer. Further investigations have shown that lncRNAs have altered expression patterns in ocular tissues and cell lines during pathological conditions. The pathogenesis of various ocular diseases, including glaucoma, cataract, corneal diseases, proliferative vitreoretinopathy, diabetic retinopathy, and retinoblastoma, is influenced by the involvement of specific lncRNAs which play a critical role in the development and progression of these diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-researched lncRNA in the context of ocular diseases, which has been shown to exert its biological effects through several signaling pathways and downstream targets. The present review provides a comprehensive summary of the molecular mechanisms underlying the biological functions and roles of MALAT1 in ocular diseases.

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Glaucoma – risk factors and current challenges in the diagnosis of a leading cause of visual impairment

Cited by 39 publications

References 115 publications

Mitochondrial dysfunction in glaucomatous degeneration

Mitochondrial dysfunction in glaucomatous degeneration

Quantitative differentiation of benign and misfolded glaucoma-causing myocilin variants on the basis of protein thermal stability

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases

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