Angioid Streaks Associated with Hereditary Spherocytosis

McLane, Nick J.; Grizzard, W. Sanderson; Kousseff, Boris G.; Hartmann, Robert C.; Sever, Raymond J.

doi:10.1016/s0002-9394(14)76127-6

Cited by 32 publications

(17 citation statements)

References 7 publications

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“…This concept is strengthened by the report of angioid streaks in other hemolytic states, including inherited spherocytosis and congenital dyserythropoietic anemia type III. 56,57 Many studies, however, failed to reveal a statistical relationship between the elastic tissue defects and patients' hematologic parameters. The hemoglobin or serum ferritin levels, the number of blood units received, or the chelation history have not so far been found to have a significant prognostic value.…”

Section: Pathogenesis and Geneticsmentioning

confidence: 99%

Elastic tissue abnormalities resembling pseudoxanthoma elasticum in β thalassemia and the sickling syndromes

Aessopos

Farmakis

Loukopoulos

2002

Blood

139

124

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The development of clinical and histopathologic manifestations of a diffuse elastic tissue defect, resembling inherited pseudoxanthoma elasticum (PXE), has been encountered with a notable frequency in patients with ␤ thalassemia, sickle cell disease, and sickle thalassemia. The PXE-like clinical syndrome, consisting of skin, ocular, and vascular manifestations, has a variable severity in these hemoglobinopathies and it is age-dependent, with a generally late onset, after the second decade of life. The defect is believed to be acquired rather than inherited and related to the consequences of the primary disease. The high prevalence of the findings implicates the elastic tissue injury as one of the main comorbid abnormalities encountered in ␤ thalassemia and the sickling syndromes. In these patients a number of complications, sometimes serious, has been recognized to be related to ocular and vascular elastic tissue defects. Because several organ systems are involved, each medical specialty should be aware of the phenomenon. This coexistence, on the other hand, introduces a novel pathogenetic aspect of PXE and an important research challenge. (Blood. 2002;99:30-35)

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Section: Pathogenesis and Geneticsmentioning

confidence: 99%

Elastic tissue abnormalities resembling pseudoxanthoma elasticum in β thalassemia and the sickling syndromes

Aessopos

Farmakis

Loukopoulos

2002

Blood

139

124

View full text Add to dashboard Cite

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“…Diffuse elastic fiber defects, resembling those reported in inherited pseudoxanthoma elasticum, have also been detected in patients with ␤-thalassaemia and sickle cell anemia (30), and in other hemolytic anemias (31,32). The genetic basis for these diseases cannot be directly linked to any structural or regulatory components involved in elastic fiber production (30,33,34).…”

mentioning

confidence: 94%

Fluctuations of Intracellular Iron Modulate Elastin Production

Bunda

Kaviani

Hinek

2005

Journal of Biological Chemistry

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Production of insoluble elastin, the major component of elastic fibers, can be modulated by numerous intrinsic and exogenous factors. Because patients with hemolytic disorders characterized with fluctuations in iron concentration demonstrate defective elastic fibers, we speculated that iron might also modulate elastogenesis. In the present report we demonstrate that treatment of cultured human skin fibroblasts with low concentration of iron 2-20 M (ferric ammonium citrate) induced a significant increase in the synthesis of tropoelastin and deposition of insoluble elastin. Northern blot and realtime reverse transcription-PCR analysis revealed that treatment with 20 M iron led to an increase of ϳ3-fold in elastin mRNA levels. Because treatment with an intracellular iron chelator, desferrioxamine, caused a significant decrease in elastin mRNA level and consequent inhibition of elastin deposition, we conclude that iron facilitates elastin gene expression. Our experimental evidence also demonstrates the existence of an opposite effect, in which higher, but not cytotoxic concentrations of iron (100 -400 M) induced the production of intracellular reactive oxygen species that coincided with a significant decrease in elastin message stability and the disappearance of iron-dependent stimulatory effect on elastogenesis. This stimulatory elastogenic effect was reversed, however, in cultures simultaneously treated with high iron concentration (200 M) and the intracellular hydroxyl radical scavenger, dimethylthiourea. Thus, presented data, for the first time, demonstrate the existence of two opposite iron-dependent mechanisms that may affect the steady state of elastin message. We speculate that extreme fluctuations in intracellular iron levels result in impaired elastic fiber production as observed in hemolytic diseases.Mature elastic fibers and laminae provide extensibility and elastic recoil to vascular walls and ligaments and form a connective tissue framework of lungs, elastic cartilage, and skin (1, 2). They are complex structures made of polymeric (insoluble) elastin and 12-nm microfibrils that consist of several glycoproteins, e.g. fibrillins, fibulins, and microfibril-associated glycoproteins (3-6). Elastic fiber formation (elastogenesis) is a complex process involving several intracellular and extracellular events. Cells (fibroblasts, endothelial cells, chondroblasts, or vascular smooth muscle cells) must first synthesize and secrete numerous glycoproteins to form a microfibrillar scaffold upon which tropoelastin, the precursor peptides, are properly assembled and covalently cross-linked by lysyl oxidase into a resilient polymer, insoluble elastin (7-10). Production of elastin reaches its highest levels in the third trimester of the fetal life and steadily decreases during early postnatal development (11,12). In undisturbed tissues, elastic fibers may last over the entire human lifespan (13,14).The net deposition of elastin appears to be controlled on both the transcriptional level (tropoelastin mRNA message express...

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“…[1,3]. This concept is strengthened by the report of angioid streaks and elastic tissue disorders in other haemolytic states, including inherited spherocytosis and congenital dyserythropoietic anaemia type III [23–25].…”

mentioning

confidence: 99%