Faulty homocysteine recycling in diabetic retinopathy.

DNA methylation Diabetic retinopathy Epigenetics Homocysteine Hydrogen sulfide Mitochondria Mitophagy Oxidative stress Retina

Journal

Eye and vision (London, England)

ISSN: 2326-0254

Titre abrégé: Eye Vis (Lond)

Pays: England

ID NLM: 101664982

Informations de publication

Date de publication:
2020

Historique:

received: 10 07 2019

accepted: 02 12 2019

entrez: 16 1 2020

pubmed: 16 1 2020

medline: 16 1 2020

Statut: epublish

Résumé

Although hyperglycemia is the main instigator in the development of diabetic retinopathy, elevated circulating levels of a non-protein amino acid, homocysteine, are also associated with an increased risk of retinopathy. Homocysteine is recycled back to methionine by methylenetetrahydrofolate reductase (MTHFR) and/or transsulfurated by cystathionine β-synthase (CBS) to form cysteine. CBS and other transsulfuration enzyme cystathionine-γ-lyase (CSE), through desulfuration, generates H Homocysteine and H Compared to age-matched nondiabetic control human donors, retina from donors with established diabetic retinopathy had ~ 3-fold higher homocysteine levels and ~ 50% lower H Compromised transsulfuration and remethylation processes play an important role in the poor removal of retinal homocysteine in diabetic patients. Thus, regulation of their homocysteine levels should ameliorate retinal mitochondrial damage, and by regulating DNA methylation status of the enzymes responsible for homocysteine transsulfuration and remethylation, should prevent excess accumulation of homocysteine.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

Homocysteine and H

RESULTS RESULTS

Compared to age-matched nondiabetic control human donors, retina from donors with established diabetic retinopathy had ~ 3-fold higher homocysteine levels and ~ 50% lower H

CONCLUSIONS CONCLUSIONS

Compromised transsulfuration and remethylation processes play an important role in the poor removal of retinal homocysteine in diabetic patients. Thus, regulation of their homocysteine levels should ameliorate retinal mitochondrial damage, and by regulating DNA methylation status of the enzymes responsible for homocysteine transsulfuration and remethylation, should prevent excess accumulation of homocysteine.

Identifiants

DOI: 10.1186/s40662-019-0167-9 PMID: 31938715 PMC: PMC6953140

pubmed: 31938715

doi: 10.1186/s40662-019-0167-9

pii: 167

pmc: PMC6953140

doi:

Types de publication

Journal Article

Langues

eng

Pagination

Subventions

Organisme : NIDDK NIH HHS

ID : P30 DK020572

Pays : United States

Organisme : NEI NIH HHS

ID : P30 EY004068

Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Déclaration de conflit d'intérêts

Competing interestsGM, NS and RAK do not have any conflict of interest.

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