Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313647450> ?p ?o ?g. }
- W4313647450 endingPage "1071" @default.
- W4313647450 startingPage "1071" @default.
- W4313647450 abstract "Age-related macular degeneration (AMD) is a major cause of blindness. Recent studies have reported impaired glycolysis in AMD patients with a high lactate/pyruvate ratio. Elevated homocysteine (Hcy) (Hyperhomocysteinemia, HHcy) was observed in several clinical studies, reporting an association between HHcy and AMD. We established the effect of HHcy on barrier function, retinal pigment epithelium (RPE) structure, and induced choroidal neovascularization (CNV) in mice. We hypothesize that HHcy contributes to AMD by inducing a metabolic switch in the mitochondria, in which cells predominantly produce energy by the high rate of glycolysis, or “Warburg”, effect. Increased glycolysis results in an increased production of lactate, cellular acidity, activation of angiogenesis, RPE barrier dysfunction, and CNV. Evaluation of cellular energy production under HHcy was assessed by seahorse analysis, immunofluorescence, and western blot experiments. The seahorse analysis evaluated the extracellular acidification rate (ECAR) as indicative of glycolysis. HHcy showed a significant increase in ECAR both in vivo using (Cystathionine β-synthase) cbs+/− and cbs−/− mice retinas and in vitro (Hcy-treated ARPE-19) compared to wild-type mice and RPE cells. Moreover, HHcy up-regulated glycolytic enzyme (Glucose transporter-1 (GlUT-1), lactate dehydrogenase (LDH), and hexokinase 1 (HK1)) in Hcy-treated ARPE-19 and primary RPE cells isolated from cbs+/+, cbs+/−, and cbs−/− mice retinas. Inhibition of GLUT-1 or blocking of N-methyl-D-aspartate receptors (NMDAR) reduced glycolysis in Hcy-treated RPE and improved albumin leakage and CNV induction in Hcy-injected mice eyes. The current study suggests that HHcy causes a metabolic switch in the RPE cells from mitochondrial respiration to glycolysis during AMD and confirms the involvement of NMDAR in this process. Therefore, targeting Glycolysis or NMDAR could be a novel therapeutic target for AMD." @default.
- W4313647450 created "2023-01-07" @default.
- W4313647450 creator A5020787558 @default.
- W4313647450 creator A5049167156 @default.
- W4313647450 creator A5057871062 @default.
- W4313647450 creator A5058435609 @default.
- W4313647450 creator A5074540577 @default.
- W4313647450 creator A5077605149 @default.
- W4313647450 creator A5080437369 @default.
- W4313647450 date "2023-01-05" @default.
- W4313647450 modified "2023-09-25" @default.
- W4313647450 title "Warburg Effect as a Novel Mechanism for Homocysteine-Induced Features of Age-Related Macular Degeneration" @default.
- W4313647450 cites W1245937174 @default.
- W4313647450 cites W1441171282 @default.
- W4313647450 cites W1548826407 @default.
- W4313647450 cites W1589173706 @default.
- W4313647450 cites W175019293 @default.
- W4313647450 cites W1893330971 @default.
- W4313647450 cites W1985070835 @default.
- W4313647450 cites W1988703517 @default.
- W4313647450 cites W1999062056 @default.
- W4313647450 cites W2002712265 @default.
- W4313647450 cites W2008363752 @default.
- W4313647450 cites W2020271577 @default.
- W4313647450 cites W2033254113 @default.
- W4313647450 cites W2035436553 @default.
- W4313647450 cites W2050140657 @default.
- W4313647450 cites W2057105708 @default.
- W4313647450 cites W2058046374 @default.
- W4313647450 cites W2060628991 @default.
- W4313647450 cites W2063649606 @default.
- W4313647450 cites W2064020686 @default.
- W4313647450 cites W2070819294 @default.
- W4313647450 cites W2074785713 @default.
- W4313647450 cites W2082660627 @default.
- W4313647450 cites W2085317787 @default.
- W4313647450 cites W2088715496 @default.
- W4313647450 cites W2088852677 @default.
- W4313647450 cites W2092788153 @default.
- W4313647450 cites W2103641796 @default.
- W4313647450 cites W2107264664 @default.
- W4313647450 cites W2127363066 @default.
- W4313647450 cites W2130213418 @default.
- W4313647450 cites W2133615329 @default.
- W4313647450 cites W2137094186 @default.
- W4313647450 cites W2144523453 @default.
- W4313647450 cites W2152421399 @default.
- W4313647450 cites W2160226180 @default.
- W4313647450 cites W2162868196 @default.
- W4313647450 cites W2163729820 @default.
- W4313647450 cites W2170431784 @default.
- W4313647450 cites W2191654248 @default.
- W4313647450 cites W2261225624 @default.
- W4313647450 cites W2286749487 @default.
- W4313647450 cites W2305989251 @default.
- W4313647450 cites W2327580634 @default.
- W4313647450 cites W2411003535 @default.
- W4313647450 cites W2559348075 @default.
- W4313647450 cites W2617421506 @default.
- W4313647450 cites W2626131839 @default.
- W4313647450 cites W2754339716 @default.
- W4313647450 cites W2794122823 @default.
- W4313647450 cites W2901655097 @default.
- W4313647450 cites W2908553539 @default.
- W4313647450 cites W2936033672 @default.
- W4313647450 cites W3009137906 @default.
- W4313647450 cites W3045746793 @default.
- W4313647450 cites W3094653946 @default.
- W4313647450 cites W3161602643 @default.
- W4313647450 cites W3198889226 @default.
- W4313647450 cites W4229663497 @default.
- W4313647450 cites W4238294480 @default.
- W4313647450 doi "https://doi.org/10.3390/ijms24021071" @default.
- W4313647450 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36674587" @default.
- W4313647450 hasPublicationYear "2023" @default.
- W4313647450 type Work @default.
- W4313647450 citedByCount "1" @default.
- W4313647450 countsByYear W43136474502023 @default.
- W4313647450 crossrefType "journal-article" @default.
- W4313647450 hasAuthorship W4313647450A5020787558 @default.
- W4313647450 hasAuthorship W4313647450A5049167156 @default.
- W4313647450 hasAuthorship W4313647450A5057871062 @default.
- W4313647450 hasAuthorship W4313647450A5058435609 @default.
- W4313647450 hasAuthorship W4313647450A5074540577 @default.
- W4313647450 hasAuthorship W4313647450A5077605149 @default.
- W4313647450 hasAuthorship W4313647450A5080437369 @default.
- W4313647450 hasBestOaLocation W43136474501 @default.
- W4313647450 hasConcept C126322002 @default.
- W4313647450 hasConcept C134018914 @default.
- W4313647450 hasConcept C181199279 @default.
- W4313647450 hasConcept C185592680 @default.
- W4313647450 hasConcept C20251656 @default.
- W4313647450 hasConcept C2777318727 @default.
- W4313647450 hasConcept C2778024200 @default.
- W4313647450 hasConcept C2779826832 @default.
- W4313647450 hasConcept C2780827179 @default.
- W4313647450 hasConcept C55493867 @default.
- W4313647450 hasConcept C62231903 @default.