A Potential Role for Fructosamine-3-Kinase in Cataract Treatment

Bruyne, Sander De; Schie, Loes van; Himpe, Jonas; Somer, Filip De; Everaert, Inge; Derave, Wim; Broecke, Caroline Van den; Huizing, Manon; Bostan, Nezahat; Speeckaert, Marijn M.; Callewaert, Nico; Aken, Elisabeth Van; Delanghe, Joris

doi:10.3390/ijms22083841

Cited by 14 publications

(21 citation statements)

References 45 publications

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“…Maximal effects on lens opacity are observed in the wavelength range of 410–430 nm, which is a typical absorbance wavelength of Maillard products that induces a yellow-brownish coloration of aged lenses. Our observations strengthen our hypothesis that the process of non-enzymatic glycation of proteins such as crystallins can be reversed [ 11 , 20 ]. Several studies have demonstrated that Maillard reactions involving sugars can induce a decrease in the chaperone function of α-crystallins [ 22 , 23 , 24 , 25 ].…”

Section: Discussionsupporting

confidence: 88%

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Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia

Delanghe

Beeckman

Beerens

et al. 2023

IJMS

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Presbyopia is an age-related vision disorder that is a global public health problem. Up to 85% of people aged ≥40 years develop presbyopia. In 2015, 1.8 billion people globally had presbyopia. Of those with significant near vision disabilities due to uncorrected presbyopia, 94% live in developing countries. Presbyopia is undercorrected in many countries, with reading glasses available for only 6–45% of patients living in developing countries. The high prevalence of uncorrected presbyopia in these parts of the world is due to the lack of adequate diagnosis and affordable treatment. The formation of advanced glycation end products (AGEs) is a non-enzymatic process known as the Maillard reaction. The accumulation of AGEs in the lens contributes to lens aging (leading to presbyopia and cataract formation). Non-enzymatic lens protein glycation induces the gradual accumulation of AGEs in aging lenses. AGE-reducing compounds may be effective at preventing and treating AGE-related processes. Fructosyl-amino acid oxidase (FAOD) is active on both fructosyl lysine and fructosyl valine. As the crosslinks encountered in presbyopia are mainly non-disulfide bridges, and based on the positive results of deglycating enzymes in cataracts (another disease caused by glycation of lens proteins), we studied the ex vivo effects of topical FAOD treatment on the power of human lenses as a new potential non-invasive treatment for presbyopia. This study demonstrated that topical FAOD treatment resulted in an increase in lens power, which is approximately equivalent to the correction obtained by most reading glasses. The best results were obtained for the newer lenses. Simultaneously, a decrease in lens opacity was observed, which improved lens quality. We also demonstrated that topical FAOD treatment results in a breakdown of AGEs, as evidenced by gel permeation chromatography and a marked reduction in autofluorescence. This study demonstrated the therapeutic potential of topical FAOD treatment in presbyopia.

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Section: Discussionsupporting

confidence: 88%

“…AGE-inhibiting or -disrupting compounds may be effective at preventing and treating AGE-related processes. FN3K has been shown to reverse crystalline glycation in cataracts [ 11 ]. This process eventually prevents AGE formation.…”

Section: Introductionmentioning

confidence: 99%

Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia

Delanghe

Beeckman

Beerens

et al. 2023

IJMS

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“…22 Some scholars believe that AGEs, duration of DM and the level of blood glucose control play an important role in the occurrence and development of this disease. 23,24 In our study on diabetic patients including a significantly larger cohort, we found that the content of AHG and AGEs in AH from patients with prolonged diabetes and poor blood glucose control was higher than that from patients with short-term diabetes and good blood glucose control. We also found a strong positive significant correlation between AHG and AGEs levels with a Pearson coefficient constant R = 0.540 (significance at the 0.01 level).…”

Section: Discussionmentioning

confidence: 60%

Concentrations of glucose metabolites in the aqueous humour of diabetic cataract eyes

Ren

Zhang

Yang

et al. 2023

European Journal of Ophthalmology

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Purpose Glucose metabolism underpins diabetic cataracts (DCs), but the relationship between the two remains unclear. Here, we tested the aqueous humour (AH) of patients with DCs to elucidate glucose metabolite levels. Methods In this study, aqueous humour (AH) samples were collected preoperatively from DC eyes (n = 37) and age-related cataract eyes (n = 37) from 74 patients (74 eyes) undergoing uncomplicated cataract surgery. The content of glucose, pyruvate, L-lactate were detected by biochemical methods and advanced glycation end-products (AGEs) was detemined using enzyme-linked immunosorbent assay (ELISA) technique. Furthermore, the ratios of glucose/pyruvate and L-lactate/pyruvate in the AH were calculated. In addition, we calculated the correlation between glucose levels and AGEs in the AH. Results The concentrations of glucose, pyruvate and AGEs in the DC group were higher than those in the control group. Significantly lower levels of L-lactate in the AH were found in the DC group. We calculated the glucose/pyruvate ratio and the L-lactate/pyruvate ratio in the AH, which showed that glucose metabolism was changed in the AH from DC patients. Interestingly, we observed that AGEs in the AH were significantly correlated with increased anterior chamber glucose permeability. A stronger correlation was found in the subgroups of male patients, younger patients, and patients with poor glycaemic control status. Conclusions Comparison of the levels of glucose metabolism-related products in the AH in the DC group highlight a potential pathological mechanism for DC from a glucose metabolism perspective. The findings indicated an alteration in the metabolic pathways of energy metabolism and amino acids in the AH of DC patients.

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“…Therefore, it would be interesting to see if a correlation between FN3K and GNEM could be found—as it exists, for example, in relation to diabetes mellitus [ 155 , 156 ]. A recent study investigating the effect of ex vivo intravitreal FN3K injections on AGE-based cataracts seems to be quite promising as a potential new treatment of certain types of cataracts [ 157 ]. Therefore, it might be good to see if glucose-derived glycation products play a role in GNEM and whether activating the FN3K in muscle cells—maybe it might be possible to inject FN3K-solutions directly into the muscle (i.m.…”

Section: Discussion and Outlookmentioning

confidence: 99%

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

et al. 2023

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Mutations in the gene coding for the bi-functional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of the sialic acid biosynthesis, are responsible for autosomal-recessive GNE myopathy (GNEM). GNEM is an adult-onset disease with a yet unknown exact pathophysiology. Since the protein appears to work adequately for a certain period of time even though the mutation is already present, other effects appear to influence the onset and progression of the disease. In this study, we want to investigate whether the late onset of GNEM is based on an age-related effect, e.g., the accumulation of post-translational modifications (PTMs). Furthermore, we also want to investigate what effect on the enzyme activity such an accumulation would have. We will particularly focus on glycation, which is a PTM through non-enzymatic reactions between the carbonyl groups (e.g., of methylglyoxal (MGO) or glyoxal (GO)) with amino groups of proteins or other biomolecules. It is already known that the levels of both MGO and GO increase with age. For our investigations, we express each domain of the GNE separately, treat them with one of the glycation agents, and determine their activity. We demonstrate that the enzymatic activity of the N-acetylmannosamine kinase (GNE-kinase domain) decreases dramatically after glycation with MGO or GO—with a remaining activity of 13% ± 5% (5 mM MGO) and 22% ± 4% (5 mM GO). Whereas the activity of the UDP-N-acetylglucosamine 2-epimerase (GNE-epimerase domain) is only slightly reduced after glycation—with a remaining activity of 60% ± 8% (5 mM MGO) and 63% ± 5% (5 mM GO).

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A Potential Role for Fructosamine-3-Kinase in Cataract Treatment

Cited by 14 publications

References 45 publications

Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia

Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia

Concentrations of glucose metabolites in the aqueous humour of diabetic cataract eyes

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

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