WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy
© 2024. The Author(s)..
BACKGROUND: In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.
METHOD: Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.
RESULT: Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.
CONCLUSIONS: WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Journal of translational medicine - 22(2024), 1 vom: 06. März, Seite 245 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Bolin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Diabetic retinopathy |
|---|
| Anmerkungen: |
Date Completed 08.03.2024 Date Revised 12.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12967-024-05046-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369387090 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369387090 | ||
| 003 | DE-627 | ||
| 005 | 20240312234059.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240307s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12967-024-05046-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1324.xml |
| 035 | |a (DE-627)NLM369387090 | ||
| 035 | |a (NLM)38448948 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Bolin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.03.2024 | ||
| 500 | |a Date Revised 12.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR | ||
| 520 | |a METHOD: Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting | ||
| 520 | |a RESULT: Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability | ||
| 520 | |a CONCLUSIONS: WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Diabetic retinopathy | |
| 650 | 4 | |a Glycolysis | |
| 650 | 4 | |a Photoreceptor cell | |
| 650 | 4 | |a Retinal neuronal degeneration | |
| 650 | 4 | |a Wnt-inhibitory factor 1 | |
| 650 | 7 | |a Glucose Transporter Type 1 |2 NLM | |
| 650 | 7 | |a Wif1 protein, mouse |2 NLM | |
| 700 | 1 | |a Zou, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Lihui |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Yinjun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bowen |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jinhaohao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fangling |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Huizhuo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of translational medicine |d 2003 |g 22(2024), 1 vom: 06. März, Seite 245 |w (DE-627)NLM142679194 |x 1479-5876 |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:1 |g day:06 |g month:03 |g pages:245 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12967-024-05046-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 1 |b 06 |c 03 |h 245 | ||