Association between vascular comorbidity and glaucoma progression: A four-year observational study

Dascălu, Ana Maria; Stana, Daniela; Nicolae, Vanesa Andrada; Cîrstoveanu, Cătălin; Vancea, G; Şerban, Dragoş; Socea, Bogdan

doi:10.3892/etm.2021.9714

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…59 The PLTP gene encodes the lipid transfer protein, which transfers lipopolysaccharides, α-tocopherol, diacylglycerol, cerebroside and may contribute to the development of metabolic syndrome, insulin resistance, obesity, atherosclerosis, and type II diabetes, etc.. 60 There is evidence that systemic comorbidities associated with hyperglycemia, hyperlipidemia, endothelial lesions, and atherosclerosis can lead to damage to the retinal nerve fiber layer and the underlying conjunctive tissue. 1,61,62 Besides, PLTP may be involved in signal transduction pathways in human neurons 63 and may contribute to maintaining integrity of the blood-brain barrier, possibly through its involvement in transfer of vitamin E and modulation of the cerebrovascular oxidative stress. 64 One more candidate gene for POAG suggested by the in silico analysis, SLC12A5 , modulates Ca 2+ -dependent insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

Ponomarenko

Reshetnikov

Dvornyk

et al. 2022

European Journal of Ophthalmology

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Purpose The aim of this study was to investigate the role of functionally significant loci of the matrix metalloproteinases genes 1, 3, 9 ( MMP1, MMP3, and MMP9) in the development of primary open-angle glaucoma (POAG) in Caucasians of the Central region of Russia. Methods In total 604 participants were recruited for the study, including 208 patients with POAG and 396 healthy controls. They were genotyped at eight single nucleotide polymorphisms (SNPs) of the three MMP genes. The association was analyzed using logistic and log-linear regression. POAG-associated loci and their proxies were in silico assessed for their functional prediction. Results Variant allele G*rs2250889 of MMP9 was significantly associated with higher risk of POAG (ORcov = 1.57–1.71). Haplotype CCA [rs3918242-rs3918249-rs17576] of the MMP9 gene was associated with lower risk of POAG (ORcov = 0.33). Allele А*rs3787268 of MMP9 was associated with the low intraocular pressure in the POAG patients (βcov = −0.176 - −0.272), and so were haplotypes AA [rs17576-rs3787268] (βcov = −0.577) and AAC [rs17576-rs3787268- rs2250889] (βcov = −0.742) of the same gene, whereas allele 2G*rs1799750 of MMP1 was associated with the earlier onset of the disease (βcov = −0.112 - −0.218). In silico analysis of the polymorphisms suggested the functionality of POAG-associated SNPs and their proxies (epigenetic potential, expression and alternative splicing effects for several genes). Conclusions The MMP9 gene polymorphisms are associated with POAG and intraocular pressure in POAG patients; rs1799750 of MMP1 was associated with the earlier age of manifestation of the disease symptoms.

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Section: Discussionmentioning

confidence: 99%

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

Ponomarenko

Reshetnikov

Dvornyk

et al. 2022

European Journal of Ophthalmology

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“…From the results of logistic regression analysis, we found that experiencing migraines significantly influences the diagnosis of OHT vs. OAG. Peripheral vasospasm is vascular dysregulation (altered vasoconstriction and/or vasodilation) of the microvasculature that is manifests as symptoms of cold hands and feet [ 73 ] and is associated with glaucoma risk and progression [ 74 , 75 ]. We identified this symptomatology in 25% of our OHTG and 31% of our OAGG populations.…”

Section: Discussionmentioning

confidence: 99%

Impact of Systemic Comorbidities on Ocular Hypertension and Open-Angle Glaucoma, in a Population from Spain and Portugal

García–Villanueva

Millá

Bolarín

et al. 2022

JCM

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Open-angle glaucoma (OAG), the most prevalent clinical type of glaucoma, is still the main cause of irreversible blindness worldwide. OAG is a neurodegenerative illness for which the most important risk factor is elevated intraocular pressure (IOP). Many questions remain unanswered about OAG, such as whether nutritional or toxic habits, other personal characteristics, and/or systemic diseases influence the course of glaucoma. As such, in this study, we performed a multicenter analytical, observational, case–control study of 412 participants of both sexes, aged 40–80 years, that were classified as having ocular hypertension (OHT) or OAG. Our primary endpoint was to investigate the relationship between specific lifestyle habits; anthropometric and endocrine–metabolic, cardiovascular, and respiratory events; and commonly used psychochemicals, with the presence of OHT or OAG in an ophthalmologic population from Spain and Portugal. Demographic, epidemiological, and ocular/systemic clinical data were recorded from all participants. Data were analyzed using the R Statistics v4.1.2 and RStudio v2021.09.1 programs. The mean age was 62 ± 15 years, with 67–80 years old comprising the largest subgroup sample of participants in both study groups. The central corneal thickness (ultrasound pachymetry)-adjusted IOP (Goldman tonometry) in each eye was 20.46 ± 2.35 and 20.1 ± 2.73 mmHg for the OHT individuals, and 15.8 ± 3.83 and 16.94 ± 3.86 mmHg for the OAG patients, with significant differences between groups (both p = 0.001). The highest prevalence of the surveyed characteristics in both groups was for overweight/obesity and daily coffee consumption, followed by psychochemical drug intake, migraine, and peripheral vasospasm. Our data show that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from OHT to OAG in this Spanish and Portuguese population.

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“…Glaucoma is a devastating optic neuropathy afflicting millions worldwide, and yet the complex etiology of the disease results in the ensuing neurodegeneration not receiving effective treatment for many individuals. While the past understanding and treatment of the disease has focused on controlling IOP, the only current modifiable risk factor, recent research has elucidated a substantial contribution of retinal vasculature dysfunction to disease progression [ 3 , 7 , 9 , 34 ]. Whether vascular dysfunction occurs early in glaucoma triggering neurodegenerative events, or whether RGC degeneration leads to the disruption of NVC remains challenging to determine.…”

Section: Discussionmentioning

confidence: 99%

“…Glaucoma shares comorbidities with a number of systemic vascular diseases, including diastolic hypotension, diabetes, ischemic cardiac disease, peripheral vasospasm, and arterial hypertension [ 7 , 8 ]. Advances in vascular imaging technology have provided evidence of a link between vascular dysfunction and glaucoma in both animal models and in the clinic [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

cGMP Signaling in the Neurovascular Unit—Implications for Retinal Ganglion Cell Survival in Glaucoma

2022

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Glaucoma is a progressive age-related disease of the visual system and the leading cause of irreversible blindness worldwide. Currently, intraocular pressure (IOP) is the only modifiable risk factor for the disease, but even as IOP is lowered, the pathology of the disease often progresses. Hence, effective clinical targets for the treatment of glaucoma remain elusive. Glaucoma shares comorbidities with a multitude of vascular diseases, and evidence in humans and animal models demonstrates an association between vascular dysfunction of the retina and glaucoma pathology. Integral to the survival of retinal ganglion cells (RGCs) is functional neurovascular coupling (NVC), providing RGCs with metabolic support in response to neuronal activity. NVC is mediated by cells of the neurovascular unit (NVU), which include vascular cells, glial cells, and neurons. Nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling is a prime mediator of NVC between endothelial cells and neurons, but emerging evidence suggests that cGMP signaling is also important in the physiology of other cells of the NVU. NO-cGMP signaling has been implicated in glaucomatous neurodegeneration in humans and mice. In this review, we explore the role of cGMP signaling in the different cell types of the NVU and investigate the potential links between cGMP signaling, breakdown of neurovascular function, and glaucoma pathology.

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Association between vascular comorbidity and glaucoma progression: A four-year observational study

Cited by 17 publications

References 43 publications

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

Impact of Systemic Comorbidities on Ocular Hypertension and Open-Angle Glaucoma, in a Population from Spain and Portugal

cGMP Signaling in the Neurovascular Unit—Implications for Retinal Ganglion Cell Survival in Glaucoma

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