The cornea and disorders of lipid metabolism

Barchiesi, Barbara J.; Eckel, Robert H.; Ellis, Philip P.

doi:10.1016/0039-6257(91)90205-t

Cited by 108 publications

(57 citation statements)

References 140 publications

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“…The disease is characterized by accumulations of phospholipid, unesterified cholesterol, cholesterol ester, and apolipoproteins AI, AII, and E in the corneal stroma (56,57). There is no clear association of plasma cholesterol levels with the disease; some affected individuals exhibit dyslipidemia but others have normal levels (58). The evidence suggests a local defect in HDL cholesterol metabolism or transport.…”

Section: Discussionmentioning

confidence: 88%

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model

Welch

Bretschger

Latib

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF͞Ei ؋ B6.129S7-Ldlr tm1Her ) ؋ C57BL͞ 6J-Ldlr tm1Her backcross mice, homozygous for the Ldlr null allele, were fed a Western-type diet for 3 months and then killed for quantification of aortic lesions. A genome scan was carried out by using DNA pools and microsatellite markers spaced at Ϸ18-centimorgan intervals. Quantitative trait locus analysis of individual backcross mice confirmed linkages to chromosomes 4 (Athsq1, logarithm of odds ‫؍‬ 6.2) and 6 (Athsq2, logarithm of odds ‫؍‬ 6.7). Athsq1 affected lesions in females only whereas Athsq2 affected both sexes. Among females, the loci accounted for Ϸ50% of the total variance of lesion area. The susceptible allele at Athsq1 was derived from the MOLF͞Ei genome whereas the susceptible allele at Athsq2 was derived from C57BL͞6J. Inheritance of susceptible alleles at both loci conferred a 2-fold difference in lesion area, suggesting an additive effect of Athsq1 and Athsq2. No associations were observed between the quantitative trait loci and levels of plasma total cholesterol, high density lipoprotein cholesterol, non-high density lipoprotein cholesterol, insulin, or body weight. We provide strong evidence for complex inheritance of atherosclerosis in mice with elevated plasma low density lipoprotein cholesterol and show a major influence of nonlipoprotein-related factors on disease susceptibility. Athsq1 and Athsq2 represent candidate susceptibility loci for human atherosclerosis, most likely residing on chromosomes 1p36 -32 and 12p13-12, respectively.

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Section: Discussionmentioning

confidence: 88%

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model

Welch

Bretschger

Latib

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…The most common include gout, renal, and gall stones, but more rare forms of crystals have been described as the result of genetic errors, leading to accumulation of certain proteins and/or molecules and causing crystal deposits in the cornea of the eye or connective tissues (ie, ochronosis), triggering inflammation. [86][87][88][89][90] In gout, monosodium urate crystals have been demonstrated to trigger the danger gene signal to initiate an inflammatory response. 88 The same has now been confirmed for cholesterol crystals.…”

Section: Discussion and Summarymentioning

confidence: 99%

Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation

Abela

2010

Journal of Clinical Lipidology

155

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“…In the present family, 2 of the 3 examined subjects with SCCD had genua valga (IL-2 and IV-4), present also in another relative (II-4) without eye problems. The relationship between genua valga and SCCD is still unclear: Huoang-Xuang et al [1985] postulated an alteration in a pleiotropic gene with variable penetrance and expressivity, whereas Barchiesi et al [1991] suggested that they are inherited as independent traits.…”

Section: Discussionmentioning

confidence: 99%

Schnyder corneal crystalline dystrophy: Description of a new family with evidence of abnormal lipid storage in skin fibroblasts

et al. 1998

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Schnyder corneal crystalline dystrophy (SCCD) comprises corneal opacities often associated with precocious arcus senilis and genua valga. The metabolic defect seems to be related to abnormal lipid storage in the central part of the cornea, especially the anterior stroma, consisting mainly of nonesterified cholesterol. Plasma lipid levels are not always increased suggesting that the disease may be due to abnormal lipid metabolism limited to the cornea. We observed a family with typical SCCD, in 1 case associated with mental retardation and mild cerebellar hypoplasia. Results of serum lipid analysis of all patients were normal. Ultrastructural study of a skin biopsy specimen and fibroblast pellet showed membrane-bound spherical vacuoles containing lipid material. Cultured fibroblasts stained by filipin, a fluorescent probe that specifically binds unesterified cholesterol, showed abnormal cytoplasmic fluorescent material, suggesting abnormal cholesterol metabolism. The presence of neurological impairment, associated with SCCD in 1 of our cases, may be regarded as coincidental. Evidence of storage lipids in skin and cultured fibroblasts suggests that the disorder of intracellular cholesterol metabolism is not limited to the cornea and that skin biopsy may be a useful method to confirm the diagnosis.

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The cornea and disorders of lipid metabolism

Cited by 108 publications

References 140 publications

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model

Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation

Schnyder corneal crystalline dystrophy: Description of a new family with evidence of abnormal lipid storage in skin fibroblasts

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