Retinal vascular integrity following correction of diabetic ketoacidosis in children and adolescents

Martin, Silas; Hoffman, William H.; Marcus, Dennis M.; Passmore, Gregory G.; Dalton, Rory R.

doi:10.1016/j.jdiacomp.2004.08.005

Cited by 9 publications

(12 citation statements)

References 32 publications

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“…Interestingly, as described above, no discrepancy in lipid ion abundances were observed between the internal standard and ‘internal standard free’ methods for the 36 week retina samples. This is consistent with results from a previous study, suggesting that the retina is protected from perturbations due to diabetic ketoacidosis 74. Differences in the abundances of several individual GPCho molecular lipid species were determined between the diabetic and control erythrocyte extracts, 36 weeks post STZ treatment.…”

Section: Resultssupporting

confidence: 91%

Analysis of Retina and Erythrocyte Glycerophospholipid Alterations in a Rat Model of Type 1 Diabetes

Lydic

Renis

Busik

et al. 2009

JALA: Journal of the Association for Laboratory Automation

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A n automated tandem mass spectrometryebased analysis using precursor ion and neutral loss scans in a triple quadrupole (QqQ) mass spectrometer has been used to identify and quantify changes in the abundances of glycerophospholipids extracted from retina and erythrocytes in a rat streptozotocin model of type 1 diabetes, 6 and 36 weeks after the induction of diabetes, compared with age-matched nondiabetic controls. The utility of an ''internal standard'' method compared with an ''internal standard free'' method for quantification of differences in the abundances of specific lipid ions was evaluated in both retina and erythrocyte lipid extracts. In retina, equivalent results were obtained by using the internal standard and internal standard free methods for quantification. In erythrocytes, the two methods of analysis yielded significantly different results, suggesting that factors intrinsic to particular sample types may influence the outcome of label-free lipidome quantification approaches.Overall increases (w25e35%) in the abundances of major retina glycerophospholipid classes were demonstrated in rats at 6 weeks of diabetes, relative to control animals. However, at 36 weeks of diabetes, subsequent overall decreases in retina glycerophosphatidylcholine (GPCho) and glycerophosphatidylethanolamine (GPEtn) abundances of 16% and 33%, respectively, were observed. Additionally, retina and erythrocyte GPCho lipids at both 6 and 36 weeks of diabetes exhibited increased incorporation of linoleic acid (18:2n6) and a decrease in docosahexaenoic acid (DHA (22:6n3) ) content. Finally, an approximately fivefold increase in the abundances of specific glycated GPEtn (Amadori-GPEtn) lipids were observed in the retina of 36-week diabetic rats, with a corresponding 1.6-fold increase of Amadori-GPEtn lipids in diabetic erythrocytes. (JALA 2009;14:383-99)

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Section: Resultssupporting

confidence: 91%

Analysis of Retina and Erythrocyte Glycerophospholipid Alterations in a Rat Model of Type 1 Diabetes

Lydic

Renis

Busik

et al. 2009

JALA: Journal of the Association for Laboratory Automation

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“…Pericyte coverage is an important step in vascular maturation (Baffi et al, 2000; Dosso et al, 1999; Israely et al, 2003; Martin et al, 2005). Different from the mature retinal vasculature, in which endothelial cells are covered by mural cells (pericytes and vascular smooth muscle cells), the neovasculature in the sub-retinal space of Vldlr −/− mice lacks functional mural cells, which may also contribute to the immaturity and instability of blood vessels.…”

Section: Discussionmentioning

confidence: 99%

“…Different from the mature retinal vasculature, in which endothelial cells are covered by mural cells (pericytes and vascular smooth muscle cells), the neovasculature in the sub-retinal space of Vldlr −/− mice lacks functional mural cells, which may also contribute to the immaturity and instability of blood vessels. Although the blood-retinal barrier primarily relies on the tight junction between endothelial cells, recent studies showed that functional pericytes also play an important role in maintaining the functional integrity of the blood-retinal barrier (Martin et al, 2005). Therefore, the lack of pericytes may contribute to the vascular leakage in Vldlr −/− mouse retina.…”

Section: Discussionmentioning

confidence: 99%

Photoreceptor degeneration and retinal inflammation induced by very low-density lipoprotein receptor deficiency

Chen

Moiseyev

et al. 2009

Microvascular Research

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Our previous studies have shown that very low-density lipoprotein receptor (VLDLR) is a negative regulator of the Wnt pathway. The present study showed that VLDLR gene knockout (Vldlr −/− ) mice displayed impaired cone ERG responses at early ages. Immunostaining of mid-wavelength cones showed significantly decreased cone densities in the retina and shortened cone outer segments in Vldlr −/− mice. At older ages, Vldlr −/− mice displayed declined rod ERG responses, decreased layers of photoreceptor nuclei, reduced rhodopsin levels and decreased levels of 11-cis retinal, the chromophore of visual pigments. As shown by fluorescein angiography and permeability assay, Vldlr −/− mice had severe retinal vascular leakage. ZO-1, a tight junction protein, was down-regulated in Vldlr −/− mouse retinae, further supporting the impaired blood-retinal barrier. Double staining of pericytes and endothelial cells in retinal sections revealed that neovasculature in Vldlr −/− mice lacks pericyte coverage, suggesting impaired maturation of retinal vasculature in Vldlr −/− mice. Staining of adherent leukocytes in the retinal vasculature revealed significant leukostasis in Vldlr −/− mice. Moreover, Vldlr −/− mice displayed up-regulated expression of multiple pro-inflammatory factors and activated NF-κB and HIF-1α, key regulators of inflammation. These findings suggest that deficiency of VLDLR leads to retinal degeneration and inflammation.

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“…One limitation of the model is that the action of lipoproteins occurs only as a secondary effect of BRB leakage, not as the primary initiator. BRB impairment may be caused by many common, intermittent metabolic stresses that are present in diabetes, such as high and fluctuating glucose, free fatty acids, oxidative stress and osmotic stress [50-54], all of which may be acutely exacerbated during episodes of ketoacidosis. Extravasation of lipoproteins, we suggest, can gradually turn a transitory BRB impairment into prolonged, chronic pathology.…”

Section: A Unifying Hypothesis For Lipoproteins In Drmentioning

confidence: 99%

Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina

Lyons²

2013

J Clin Exp Ophthalmol

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Clinical epidemiological studies have revealed relatively weak, yet statistically significant, associations between dyslipidemia/dyslipoproteinemia and diabetic retinopathy (DR). Recent large interventional studies, however, demonstrated an unexpectedly robust efficacy of fenofibrate on the development of DR, possibly independent of plasma lipids. To unify the apparent discrepancies, we hypothesize that plasma lipoproteins play an indirect but important role in DR, contingent on the integrity of the blood-retina-barrier (BRB). In retinas with an intact BRB, plasma lipoproteins may be largely irrelevant; however, important effects become operative after the BRB is impaired in diabetes, leading to lipoprotein extravasation and subsequent modification, hence toxicity to the neighbouring retinal cells. In this hypothesis, BRB leakage is the key, plasma lipoprotein concentrations mainly modulate its consequences, and fenofibrate has intra-retinal actions. This review summarizes our current knowledge of the direct effects and mechanisms of modified lipoproteins on retinal cells and their potential contribution to the pathogenesis of DR.

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Retinal vascular integrity following correction of diabetic ketoacidosis in children and adolescents

Cited by 9 publications

References 32 publications

Analysis of Retina and Erythrocyte Glycerophospholipid Alterations in a Rat Model of Type 1 Diabetes

Analysis of Retina and Erythrocyte Glycerophospholipid Alterations in a Rat Model of Type 1 Diabetes

Photoreceptor degeneration and retinal inflammation induced by very low-density lipoprotein receptor deficiency

Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina

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