Cardiovascular repercussions of the pseudoexfoliation syndrome

Katsi, Vasiliki; Pavlidis, Antonios N.; Kallistratos, Manolis S.; Fitsios, Athanasios; Bratsas, Athanasios; Tousoulis, Dimitris; Stefanadis, Christodoulos; Manolis, Athanasios; Kallikazaros, Ioannis

doi:10.4103/1947-2714.117294

Cited by 31 publications

(11 citation statements)

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“…A large number of studies have been presented indicating impaired circulation in various tissues and vital organs in persons with PES ( Akarsu and Ünal, 2005 , Atalar et al, 2006 , Andrikopoulos et al, 2014 , Cumurcu et al, 2013 , Djordjevic-Jocic et al, 2012 , French et al, 2012 , Gonen et al, 2013 , Katsi et al, 2013 , Mitchell et al, 1997 , Praveen et al, 2011 , Turacli et al, 2007 , Visontai et al, 2008 ). It is unlikely that increased prevalence of serious diseases, like heart attack and stroke, would not influence mortality and life span.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, a number of observations indicate that PES may have functional implications beyond the eye ( Bettis et al, 2014 , Katsi et al, 2013 , Tarkkanen et al, 2008 ), although opinion is divided with regards to its significance ( Andrikopoulos et al, 2014 , Gonen et al, 2013 , Hietanen et al, 2002 , Ringvold, 2001 , Schumacher et al, 2001 , Tarkkanen, 2008 ). Recently, the association between ocular PES and vascular disease has been evaluated in a meta-analysis based on sixteen epidemiologic studies ( Wang et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Ocular pseudoexfoliation syndrome and life span

2015

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BackgroundTo compare life span of persons with and without ocular pseudoexfoliation syndrome (PES).MethodsThe study is based on an epidemiological survey conducted in Sør-Trøndelag county, Norway, in 1985–86. All inhabitants over 64 years of age (2109 individuals) were invited. Mortality information was obtained from The Norwegian Institute of Public Health in 2014, by which time 99% of the participants were deceased.ResultsWhen adjusting for age and gender, life span was not statistically different in persons with and without PES. Following the diagnosis of PES, patients' survival was up to, and beyond, 30 years.ConclusionsOur observations suggest that, despite all the systemic aberrations reported in persons with ocular PES, none or only marginal functional changes are caused in extraocular organs and tissues. The present study supports the notion that systemic PES is not a life-threatening condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ocular pseudoexfoliation syndrome and life span

2015

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“…XFM incorporates many extracellular matrix proteins, proteases and protease inhibitors, including clusterin, ApoE, latent TGFβ binding proteins, fibrillins, fibulins, lysosomal hydrolases and most notably LOXL1, a crosslinking enzyme needed for elastin fiber formation 2–4 . While there are reports showing health impact in multiple organs, in particular in peri-cardiac vessels 5 , the most significant morbidity occurs in the eye 6–8 . Patients presenting with elevated intraocular pressure (IOP) and XFM have a significantly higher chance of developing glaucoma (XFG) with subsequent vision loss compared to those without the presence of XFM.…”

Section: Introductionmentioning

confidence: 99%

Exfoliation Syndrome: A Disease of Autophagy and LOXL1 Proteopathy

Bernstein

Ritch

Wolosin

2018

Journal of Glaucoma

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Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (exfoliation material) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where exfoliation material accumulations form on the surface of the ciliary body, iris, and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies. Progress in understanding the cellular bases for XFS/XFG has been slowed by a lack of experimental models. Working with primary human tenon fibroblasts (TF) derived from trabeculectomies of XFG patients and age-matched primary open-glaucoma controls, we found that TF from XFG cells display many of the functional features observed in cells from other protein aggregate diseases, such as Parkinson, Alzheimer, Huntington, and age-related macular degeneration. We have documented defects in lysosomal positioning, microtubule organization, autophagy processing rate, and mitochondrial health. In regard to failure of lysosomal and autophagosome positioning in XFG cells, we have found that XFG TF are unable to establish the transnuclear microtubule organizing center that is required for efficient centripetal vesicular locomotion along microtubules. In regard to potential sources of the autophagy malfunction, we have directed our attention to a potential role of the lysyl oxidase-like 1 protein (LOXL1), the elastic fiber catalyst that displays variant-dependent association with risk for XFG. Our experiments show that (a) in XFG cells, a substantial fraction of LOXL1 is processed for degradation by the autophagic system; (b) most of the LOXL1 N-terminus domain exists in a highly disordered state, a condition known to greatly increase the frequency of polypeptide misfolding; (c) that maximum misfolding occurs at amino acid position 153, the location of the high risk variant G153D; and (d) that replacement of glycine (G) by aspartate (D) there results in a substantial decrease in disorder within the 20 amino acid surrounding domain. Finally, we show that clusterin, a protein that can be induced by the presence of intracellular, or extracellular aggregates, is uniformly overexpressed in XFG TF. The implications of our results for a theory relating XFG to cellular aggregopathy are discussed.

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“…Other ocular manifestations of XFS include angle-closure glaucoma, cataract formation and retinal vein occlusion 3,4 . XFS is also associated with numerous systemic conditions, including Alzheimer’s-like dementia, sensorineural hearing loss, cerebrovascular disease, and cardiovascular disease 5 .…”

Section: Introductionmentioning

confidence: 99%

Genetics of Exfoliation Syndrome and Glaucoma

Aboobakar¹,

Allingham²

2014

International Ophthalmology Clinics

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Exfoliation glaucoma (XFG) is the most common identifiable secondary form of open-angle glaucoma in the world. It is an ocular manifestation of exfoliation syndrome (XFS), an age-related systemic disease characterized by deposition of extracellular fibrillar material in various tissues and organs. XFS/XFG has been studied in populations around the world, which has led to identification of genetic factors that play a significant role in disease pathogenesis. Here, we summarize current knowledge of the genetics of XFS/XFG and identify areas for future research.

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Cardiovascular repercussions of the pseudoexfoliation syndrome

Cited by 31 publications

References 50 publications

Ocular pseudoexfoliation syndrome and life span

Ocular pseudoexfoliation syndrome and life span

Exfoliation Syndrome: A Disease of Autophagy and LOXL1 Proteopathy

Genetics of Exfoliation Syndrome and Glaucoma

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