Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

Fokkens, Bernardina T.; Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.J.M.; Smit, Andries J.; Los, Leonoor I.

doi:10.1371/journal.pone.0173379

Cited by 17 publications

(14 citation statements)

References 49 publications

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“…Dicarbonyls, such as methylglyoxal and glyoxal, are excessively formed in diabetes mellitus patients. Upon reaction with proteins the dicarbonyls generate advanced glycation end product (AGEs) which may cause diabetic retinopathy, nephropathy, neuropathy, rheumatoid arthritis etc [ 48 – 51 ]. Participation of modified-IgG in autoimmune disorders (especially rheumatoid arthritis) has been reported by several authors [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level

et al. 2018

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Hyperglycaemia triggers increased production of methylglyoxal which can cause gross modification in proteins’ structure vis-a-vis function though advanced glycation end products (AGEs). The AGEs may initiate vascular and nonvascular pathologies. In this study, we have examined the biochemical and biophysical changes in human IgG under normal and high glucose after introducing methylglyoxal into the assay mixture. This non-enzymatic reaction mainly engaged lysine residues as indicated by TNBS results. The UV results showed hyperchromicity in modified-IgG samples while fluorescence data supported AGEs formation during the course of reaction. Shift in amide I and amide II band position indicated perturbations in secondary structure. Increase carbonyl content and decrease in sulfhydryl suggests that the modification is accompanied by oxidative stress. All modified-IgG samples showed more thermostability than native IgG; the highest Tm was shown by IgG-high glucose-MGO variant. Results of ANS, Congo red and Thioflavin T dyes clearly suggest increase in hydrophobic patches and aggregation, respectively. SEM and TEM images support aggregates generation in modified-IgG samples.

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Section: Discussionmentioning

confidence: 99%

Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level

et al. 2018

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“…Inhibition of AGE accumulation has been shown to slow the progression of established diabetes mellitus-associated atherosclerosis [30] . Methylglyoxal, which is formed by the nonenzymatic fragmentation of the glycolytic intermediate triose phosphate, is a precursor of the majority of AGE adducts in diabetes mellitus [31] . In nondiabetic apolipoprotein E (ApoE) null mice, increasing plasma methylglyoxal concentration to diabetic levels caused endothelial inflammation and atherogenesis similar to that seen in mice with diabetes mellitus [32] .…”

Section: Hyperglycemia-induced Excessive Ros Production and Acceleratmentioning

confidence: 99%

New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis

et al. 2019

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Oxidative stress and inflammation interact in the development of diabetic atherosclerosis. Intracellular hyperglycemia promotes production of mitochondrial reactive oxygen species (ROS), increased formation of intracellular advanced glycation end-products, activation of protein kinase C, and increased polyol pathway flux. ROS directly increase the expression of inflammatory and adhesion factors, formation of oxidized-low density lipoprotein, and insulin resistance. They activate the ubiquitin pathway, inhibit the activation of AMP-protein kinase and adiponectin, decrease endothelial nitric oxide synthase activity, all of which accelerate atherosclerosis. Changes in the composition of the gut microbiota and changes in microRNA expression that influence the regulation of target genes that occur in diabetes interact with increased ROS and inflammation to promote atherosclerosis. This review highlights the consequences of the sustained increase of ROS production and inflammation that influence the acceleration of atherosclerosis by diabetes. The potential contributions of changes in the gut microbiota and microRNA expression are discussed.

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“…189 AGEs has been shown to increase in the vitreous with age, especially in patients with diabetes 190 and/or rhegmatogenous retinal detachment. 191 AGE accumulation has also been shown to reduce vitreous permeability, 192 which might explain the disruption to the antioxidant balance and the oxygen gradient in liquefied vitreous. The connection between a healthy oxygen gradient, homogeneous vitreous, rate of AGE formation, and biotransport of molecules (ascorbate, glutathione, other therapeutics, etc.)…”

Section: Future Directionsmentioning

confidence: 99%

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

Tram

Maxwell

Swindle-Reilly

2020

Current Eye Research

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Research on the vitreous humor and development of hydrogel vitreous substitutes have gained a rapid increase in interest within the past two decades. However, the properties of the vitreous humor and vitreous substitutes have yet to be consolidated. In this paper, the mechanical properties of the vitreous humor and hydrogel vitreous substitutes were systematically reviewed. The number of publications on the vitreous humor and vitreous substitutes over the years, as well as their respective testing conditions and testing techniques were analyzed. The mechanical properties of the human vitreous were found to be most similar to the vitreous of pigs and rabbits. The storage and loss moduli of the hydrogel vitreous substitutes developed were found to be orders of magnitude higher in comparison to the native human vitreous. However, the reported modulus for human vitreous, which was most commonly tested in vitro, has been hypothesized to be different in vivo. Future studies should focus on testing the mechanical properties of the vitreous in situ or in vivo. In addition to its mechanical properties, the vitreous humor has other biotransport mechanisms and biochemical functions that establish a redox balance and maintain an oxygen gradient inside the vitreous chamber to protect intraocular tissues from oxidative damage. Biomimetic hydrogel vitreous substitutes have the potential to provide ophthalmologists with additional avenues for treating and controlling vitreoretinal diseases while preventing complications after vitrectomy. Due to the proximity and interconnectedness of the vitreous humor to other ocular tissues, particularly the lens and the retina, more interest has been placed on understanding the properties of the vitreous humor in recent years. A better understanding of the properties of the vitreous humor will aid in improving the design of biomimetic vitreous substitutes and enhancing intravitreal biotransport.

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Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

Cited by 17 publications

References 49 publications

Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level

Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level

New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

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