Pseudoexfoliation Syndrome Ocular Manifestation of a Systemic Disorder?

Schlötzer‐Schrehardt, Ursula; M, Koca; Naumann, G. O. H.; Volkholz, H.

doi:10.1001/archopht.1992.01080240092038

Cited by 398 publications

(306 citation statements)

References 15 publications

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“…Age related macular degeneration Drusen components Extracellular Clus (Sakaguchi et al, 2002), SAP (Ambati et al, 2003) Gelatinous drop-like corneal dystrophy Keratoepithelin Extracellular Clus (Nishida et al, 1999), SAP (Stix et al, 2005) Lattice type I corneal dystrophy M1S1 Extracellular Clus (Nishida et al, 1999), SAP (Stix et al, 2005) Pseudoexfoliation (PEX) syndrome PEX components Extracellular Clus (Zenkel et al, 2006), SAP (Schlotzer-Schrehardt et al, 1992) Down's syndrome Aβ Extracellular Clus (Kida et al, 1995), SAP (Kalaria and Grahovac 1990) Figure 1. A schematic representation of some of the fates that await polypeptide chains in vivo.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerabate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ABSTRACTThe pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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Section: Discussionmentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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“…6,7 PEX is not only an ocular disease, but also a generalized disorder that involves the abnormal production and/or turnover of extracellular matrix material. [6][7][8][9][10] Recent investigations have revealed the presence of PEX fibril in several extracellular tissues. [9][10][11] These studies have shown that the PEX material is found in many parts of the body such as the eyes, skin, heart, lungs, liver, kidney, gall bladder, blood vessels, optic nerves, and meninges.…”

mentioning

confidence: 99%

“…[6][7][8][9][10] Recent investigations have revealed the presence of PEX fibril in several extracellular tissues. [9][10][11] These studies have shown that the PEX material is found in many parts of the body such as the eyes, skin, heart, lungs, liver, kidney, gall bladder, blood vessels, optic nerves, and meninges. [9][10][11] PEX has also been shown to affect smaller vessels rather than the major ones.…”

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confidence: 99%

Pseudoexfoliation as a risk factor for peripheral vascular disease: a case-control study

Praveen

Shah

Vasavada

et al. 2010

Eye

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Aim To determine the association between pseudoexfoliation (PEX) and peripheral vascular disease (PVD) among age-related cataract. Setting Iladevi Cataract and IOL Research Center, Ahmedabad, India. Material and methods An observational agematched case-control study of 160 patients over 60 years of age with age-related cataract. A total of 40 subjects with PEX (cases) were compared with 120 subjects with cataract but without PEX (controls). A detailed medical history, including hypertension, diabetes mellitus, cerebrovascular stroke and ischaemic heart disease, was recorded. Ankle brachial index (ABI) was used to determine the risk of PVD among age-related cataract patients. Color Doppler imaging was performed on the brachial and dorsalis pedis artery to measure ABI and detect PVD. Least mean ABI was the main outcome measure, as low ABI indicates higher risk for PVD. The lowest mean ABI was measured for each subject. An ABI ratio of o0.90 was considered abnormal. The MannWhitney U-test and logistic regression were used for analysis. Results The lowest mean ABI in the controls was 0.98 ± 0.03 (SD; a range of 0.86-1.08) as compared with 0.88 ± 0.02 (SD) among the cases (a range of 0.79-0.92; Po0.001). When compared with controls, cases had a lower ABI (Po0.001) irrespective of the presence or absence of systemic illness. On multiple regression analysis adjusting for systemic illness, the presence of PEX increased the odds of a low ABI group 150 times (Po0.001). Conclusion Subjects with cataract and PEX had a significantly lower ABI as compared with controls (cataracts without PEX). PEX is associated with and may be a risk factor for PVD.

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“…A síndrome de pseudo-exfoliação (SPEX) é uma fibrilopatia relacionada à idade de causa desconhecida, caracterizada pela deposição de material pseudo-exfoliativo anormal sobre o segmento anterior do olho, além de pele, pulmão, coração, fígado, vasos sanguíneos e meninges (1)(2)(3) . A síntese ocular e a deposição crônica deste material podem levar a complicações como glaucoma de ângulo aberto e aumento em complicações de cirurgia ocular (1) .…”

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“…A síntese ocular e a deposição crônica deste material podem levar a complicações como glaucoma de ângulo aberto e aumento em complicações de cirurgia ocular (1) . A associação com oclusão de veia central da retina (4)(5) e eventos cardiovasculares (6)(7) também tem sido sugerida.…”

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Análise da correlação entre síndrome de pseudo-exfoliação e aneurisma de aorta abdominal

Filho¹,

Araújo²,

Costa³

et al. 2004

Arq. Bras. Oftalmol.

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0,05). Dois dos 65 pacientes com aneurisma de aorta e um dos 51 controles apresentaram síndrome de pseudo-exfoliação (p = 1,00). CONCLUSÃO: A prevalência de síndrome de pseudo-exfoliação em pacientes operados por aneurisma de aorta abdominal e em pacientes com aterosclerose periférica foi similar. Este achado não confirma a associação proposta entre síndrome de pseudo-exfoliação e aneurisma de aorta abdominal.]]>

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Pseudoexfoliation Syndrome Ocular Manifestation of a Systemic Disorder?

Cited by 398 publications

References 15 publications

Extracellular Chaperones and Amyloids

Extracellular Chaperones and Amyloids

Pseudoexfoliation as a risk factor for peripheral vascular disease: a case-control study

Análise da correlação entre síndrome de pseudo-exfoliação e aneurisma de aorta abdominal

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