Asymmetric Dimethyloarginin (ADMA) Concentration in the Aqueous Humor of Patients with Exfoliation Syndrome or Exfoliative Glaucoma

Mikropoulos, Dimitrios G.; Mallini, Paraskevi; Michopoulou, Anna; Giannopoulos, Theodoros; Arranz-Marquez, Esther; Κολιάκος, Γεώργιος; Konstas, Anastasios G. P.

doi:10.3109/02713683.2012.757325

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…ADMA concentrations of both aqueous humor and serum in XFS were found to be significantly higher than those measured in controls 126 . Furthermore, in another study, ADMA concentrations in aqueous humor were significantly greater in XFG patients compared to either XFS or normal cataract controls 127 .…”

Section: Risk Factors For Xfs and The Relation With Oxidation Stressmentioning

confidence: 97%

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Chiras

Kitsos

Petersen

et al. 2014

Critical Reviews in Clinical Laboratory Sciences

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Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

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Section: Risk Factors For Xfs and The Relation With Oxidation Stressmentioning

confidence: 97%

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Chiras

Kitsos

Petersen

et al. 2014

Critical Reviews in Clinical Laboratory Sciences

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“…We speculated that impaired nitric oxide signaling might be responsible for nailfold hemorrhages in POAG. 21 Interestingly, some 51,52 but not all studies 53 show that asymmetric dimethyl arginine, an inhibitor of nitric oxide synthase and contributor to endothelial cell dysfunction, is elevated in the aqueous humor and serum of XFS/XFG patients. One needs also to consider that other mechanisms may be operative in the formation of nailfold hemorrhages in XFS/XFG including a tendency for inherent blood clot formation as demonstrated by rotational thromboelastography.…”

Section: Discussionmentioning

confidence: 99%

Nailfold capillary morphology in exfoliation syndrome

Cousins

Kang

Bovee

et al. 2017

Eye

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Purpose The purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy. Patients and methods We used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥ 200 microns (μm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models. Results After adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥ 200 μm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤ 0.0001) and in POAG vs controls (P-for trend ≤ 0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend = 0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend = 0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥ 1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score o1.0 (P-for trend = 0.005). Conclusion A high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

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“…At present, the association of ADMA levels and glaucoma is somewhat controversial mainly because of the limited number of the previous studies. 13,14,21,22 The earlier study with the largest sample size of 211 patients with advanced glaucoma and 295 participants without glaucoma reported that the serum ADMA levels in advanced glaucoma were significantly higher than that of the control participants. 13 Our findings are consistent with the results of this previous study.…”

Section: Discussionmentioning

confidence: 97%

“…A few clinical studies have shown that the level of ADMA in the serum and aqueous humor of patients with glaucoma was higher than that of the control participants without glaucoma. 13,14 However, whether the ADMA levels is associated with the severity of the glaucomatous visual field damages remains to be investigated.…”

mentioning

confidence: 99%

Association Between the Asymmetric Dimethylarginine Levels and Glaucoma Severity: A Cross-Sectional Analysis of the LIGHT Study

Yoshikawa

Obayashi

Miyata

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of nitric oxide synthase, may be involved in the pathophysiology of glaucoma by dysfunctioning nitric oxide and oxidative stress. The purpose of this study was to determine whether the serum ADMA level is associated with the severity of glaucoma. METHODS.One hundred twenty-five patients with glaucoma (mean age 69.4 years) were analyzed in this cross-sectional study. The severity of glaucoma was determined by the visual field mean deviation in the worse eye; severe, a mean deviation ≤ −12 dB; and mild, a mean deviation > −12 dB. The serum ADMA levels were classified into three groups according to tertiles; low (T1), intermediate (T2), and high group (T3). RESULTS.The mean serum ADMA levels in the severe glaucoma group was significantly higher than that in the mild glaucoma group (0.41 vs. 0.39 μmol/L; P = 0.031). A significantly higher prevalence of patients with severe glaucoma was found in the T3 group than that in the T1 group (T1, 44.7% and T3, 68.2%; P = 0.018). In the multivariable logistic regression analysis adjusted for the potential confounders, e.g., age, sex, obesity, smoking, hypertension, diabetes, and renal function, the odds ratio for severe glaucoma in the T3 group was significantly higher than that in the T1 group (odds ratio 3.02; 95% confidence interval 1.04 to 8.79; P = 0.043). CONCLUSIONS.A significant association between higher serum ADMA levels and severe glaucoma was found, and this association remained significant after adjusting for the potential confounders.

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Asymmetric Dimethyloarginin (ADMA) Concentration in the Aqueous Humor of Patients with Exfoliation Syndrome or Exfoliative Glaucoma

Abstract: Aqueous humor ADMA concentration is significantly elevated in XFG patients supporting the view that oxidative stress plays a key role in XFG pathobiology. The lower level of this marker in XFS suggests that the development of XFG is a prerequisite for ADMA elevation.

Cited by 9 publications

References 32 publications

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Nailfold capillary morphology in exfoliation syndrome

Association Between the Asymmetric Dimethylarginine Levels and Glaucoma Severity: A Cross-Sectional Analysis of the LIGHT Study

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