The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities‐A review

Aboobakar, Inas F.; Wiggs, Janey L.

doi:10.1111/ceo.14035

Cited by 34 publications

(17 citation statements)

References 130 publications

(129 reference statements)

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“…About 52 XFS including those with glaucoma were screened for the variations and found that allele G of rs3825942 was significantly associated (p = 0.0001) and genotype GG (p = 0.000305) with XFS in our population, which was the first Asian study [83]. Pseudo-exfoliation glaucoma is caused by polymorphisms in the lysyl oxidase like 1 (LOXL1) gene in chromosome 15 with significant associations through GWAS in many populations across the world [81]. Pseudo-exfoliation syndrome, due to the deposition of extracellular fibrillar material (basement membrane, clusterin, elastic fibre contents, elastin, fibrillin-1, laminin, fibronectin, latent TGF-B proteins) crosslinking with LOXL1, hence systemically, it may be associated with cardiovascular diseases, cerebrovascular disorders, dementia like Alzheimer's, pelvic organ prolapse and sensory neural deafness [84].…”

Section: Complex Genetics and Genomics Of Glaucomamentioning

confidence: 95%

“…PCMTD1 (Protein-L-Isoaspartate (D-Aspartate) O-Methyltransferase Domain Containing 1) protein is of the methyltransferase superfamily and ST18 (ST18 C2H2C-Type Zinc Finger Transcription Factor) protein inhibits basal transcription activity through target promoters. There are a myriad of players implicated in PACG as predisposing traits, (extensively reviewed by Ahram et al, Aboobakar and Wiggs) like MTHFR, MFRP, CHX10, HGF, RS; PO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, ALPPL2, ZC3H11B, PRSS56, ABCC5, MYOC, CYP1B1, eNOS, PCMTD1, ST18, HSP70, SPARC, CALCRL, EPDR1, CHAT, FERMT2, DPM2, FAM102A and NEB [77,81]. A variety of anatomical, physiological, genetic and environmental factors individually or collectively result in PACG and hence, these associations reveal the larger etiopathogenesis network.…”

Section: Complex Genetics and Genomics Of Glaucomamentioning

confidence: 99%

See 1 more Smart Citation

Molecular Genomics of Glaucoma: An Update

Kumaramanickavel¹,

Jadhav²,

Ramsait³

et al. 2023

Glaucoma - Recent Advances and New Perspectives

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Glaucoma is in the top five age-related eye disorders with increasing prevalence globally. Past research has led to the understanding of glaucoma as a neurodegenerative disease. Glaucoma phenomics could be syndromic or non-syndromic. Globally primary open angle, primary angle closure and primary pseudoexfoliation glaucomas are widely present. The genetics and genomics of glaucoma are heterogeneous, both clinically and genetically. Glaucoma has heritability associations, particularly with central corneal thickness, retinal nerve fibre layer and peripapillary atrophy. Ocular embryogenesis genes when mutated could cause either local (in situ), pan-ocular or systemic syndromic glaucoma phenomics. In glaucoma, except for a few single gene causes, most of the associations have been shown with innumerable gene single-nucleotide polymorphisms and epigenetic factors. The biological mechanisms in glaucoma are mechanical strain, inflammation, oxidative stress, vascular dysregulation, and immune imbalance, which independently or collectively contribute to the neurodegeneration and visual morbidity. Biomarkers in glaucoma have experimental study biases and therefore today we cannot apply them effectively in clinical practice and henceforth that demands further research to understand the fundamental basis of the disease. However, the knowledge gained in research will translate into early detection and biomolecular interventional strategies, having traction toward personalised medicine.

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Section: Complex Genetics and Genomics Of Glaucomamentioning

confidence: 95%

Section: Complex Genetics and Genomics Of Glaucomamentioning

confidence: 99%

Molecular Genomics of Glaucoma: An Update

Kumaramanickavel¹,

Jadhav²,

Ramsait³

et al. 2023

Glaucoma - Recent Advances and New Perspectives

View full text Add to dashboard Cite

show abstract

“…It is well known that glaucoma is markedly affected by genetic factors and is a complex genetic disease ( Aboobakar and Wiggs, 2022 ). There has been evidence suggesting that small variations, including single nucleotide polymorphisms (SNPs) may be underlying cause of glaucoma.…”

Section: Pathogenesis Of Glaucomamentioning

confidence: 99%

“…Besides, these SNPs may play highly pathogenic, mildly pathogenic or protective role in causing glaucoma. Genome-wide association studies (GWAS) is a genome-wide method that compares the genetic profile of SNPs between glaucoma cases and normal groups, aimed at identifying glaucoma-associated genomic regions ( Aboobakar and Wiggs, 2022 ). Thus far, findings of GWAS have implicated 127 genetic loci that show strong associations with primary open-angle glaucoma ( Gharahkhani et al, 2021 ).…”

Section: Pathogenesis Of Glaucomamentioning

confidence: 99%

From Bench to Bed: The Current Genome Editing Therapies for Glaucoma

Rong

et al. 2022

Front. Cell Dev. Biol.

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Glaucoma is a group of optic neuropathies featured by degeneration of retinal ganglion cells and loss of their axons in the optic nerve. The only currently approved therapies focus on lowering intraocular pressure with medication and surgery. Over the previous few decades, technological advances and research progress regarding pathogenesis has brought glaucomatous gene therapy to the forefront. In this review, we discuss the three current genome editing methods and potential disease mechanisms of glaucoma. We further summarize different genome editing strategies that are being developed to target a number of glaucoma-related genes and pathways from four aspects including strategies to lower intraocular pressure, neuroprotection, RGC and optic nerve neuro-regeneration, and other strategies. In summary, genome therapy is a promising therapy for treating patients with glaucoma and has great potential to be widely applied in clinical practice.

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“… 2 , 3 Despite extensive investigation, intraocular pressure (IOP) is currently the only modifiable risk factor to prevent disease progression. 4 The development and progression of POAG are influenced by complex gene/environment interactions, 5 as well as non-modifiable factors, including IOP, age, family history, central corneal thickness, and optic disc features. 6 …”

mentioning

confidence: 99%

Blood Pressure Measures and Incident Primary Open-Angle Glaucoma

Macri

Wong

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate the association of systemic blood pressure and incident primary open-angle glaucoma (POAG) using a large open-access database. Methods Prospective cohort study included 484,268 participants from the UK Biobank without glaucoma at enrollment. Incident POAG events were recorded through assessment visits, hospital inpatient admissions, and primary care data. Blood pressure measures included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Repeated measurements throughout the study period were analyzed as time-varying covariables. The parameters were modeled as both categorical and continuous nonlinear variables. The primary outcome measure was the relative hazard of incident POAG. Results There were 2390 incident POAG events over 5,715,480 person-years of follow-up. Median follow-up was 12.08 years. In multivariable analyses, compared to SBP and PP in the normal range (SBP, 120–130 mmHg; PP, 40–50 mmHg), higher SBP and PP were associated with an increased risk of incident POAG (linear trend P = 0.038 for SBP, P < 0.001 for PP). Specifically, SBP of 130 to 140 mmHg or 140 to 150 mmHg was associated with a 1.16 higher hazard of incident POAG (95% CI, 1.01–1.32 and 1.01–1.33, respectively), whereas a PP of greater than 70 mmHg was associated with a 1.13 higher hazard of incident glaucoma (95% CI, 1.00–1.29). In multivariable models, no statistically significant associations were found for DBP or MAP with incident glaucoma. These findings were similar when blood pressure measures were modeled as continuous variables. Conclusions Higher SBP and PP were associated with an increased risk of incident POAG. Further studies are required to characterize these relationships better.

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The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities‐A review

Cited by 34 publications

References 130 publications

Molecular Genomics of Glaucoma: An Update

Molecular Genomics of Glaucoma: An Update

From Bench to Bed: The Current Genome Editing Therapies for Glaucoma

Blood Pressure Measures and Incident Primary Open-Angle Glaucoma

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