Regulation of Lysyl Oxidase-like 1 (<i>LOXL1</i>) and Elastin-Related Genes by Pathogenic Factors Associated with Pseudoexfoliation Syndrome

Zenkel, Matthias; Krysta, Anita; Pasutto, Francesca; Juenemann, Anselm; Kruse, Friedrich E.; Schlötzer‐Schrehardt, Ursula

doi:10.1167/iovs.11-8361

Cited by 83 publications

(89 citation statements)

References 37 publications

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“…Moreover, the nailfold is largely unshielded from ambient solar exposure and it is known that ultraviolet radiation alters LOXL1 expression. 37 Perhaps interaction between ambient ultraviolet rays and LOXL1 activity 38,39 contributes to the nailfold capillary morphological changes we observed.…”

Section: Discussionmentioning

confidence: 83%

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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Section: Discussionmentioning

confidence: 83%

Nailfold capillary morphology in exfoliation syndrome

Cousins

Kang

Bovee

et al. 2017

Eye

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“…They reported a decrease in TAS in the plasma of XFG patients and suggested that the combined effect of the high risk allele for both LOXL1 SNPs and the oxidative stress clearly contributed through different mechanisms to the development of XFG. Zenkel et al 115 analyzed the effect of a number of XFS-associated pathogenic factors and stress conditions on the expression of LOXL1 and elastic fiber proteins. Cultured human Tenon's capsule fibroblasts with high-and low-risk LOXL1 haplotypes were exposed to TGF-b1, interleukin-6, Hcy, oxidative stress, hypoxia or ultraviolet radiation.…”

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

confidence: 99%

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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“…Factors potentially influencing XFS pathogenesis were tested for their effect on LOXL1 expression using cultured fibroblasts from Tenon's capsule biopsies from five patients with cataract and XFS and three patients with cataract without XFS [8]. Changes in LOXL1 expression were also investigated for high and low LOXL1 risk haplotypes (based on the R141L and G153D polymorphisms) [8].…”

mentioning

confidence: 99%

Expression and Regulation of LOXL1 and Elastin-related Genes in Eyes With Exfoliation Syndrome

Wiggs

Pasquale

2014

Journal of Glaucoma

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Regulation of Lysyl Oxidase-like 1 (LOXL1) and Elastin-Related Genes by Pathogenic Factors Associated with Pseudoexfoliation Syndrome

Abstract: The findings support the notion that both genetic and nongenetic fibrogenic factors, particularly TGF-β1 and oxidative stress, may cooperate in the stable accumulation of PEX aggregates.

Cited by 83 publications

References 37 publications

Nailfold capillary morphology in exfoliation syndrome

Nailfold capillary morphology in exfoliation syndrome

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

Expression and Regulation of LOXL1 and Elastin-related Genes in Eyes With Exfoliation Syndrome

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