The role of autophagy involving the protein kinase B/sterol regulatory ele-ment binding protein 1 signaling pathway in diabetic retinopathy
10.13389/j.cnki.rao.2025.0105
- VernacularTitle:Akt/SREBP-1信号通路参与的自噬在糖尿病视网膜病变中的作用
- Author:
Li DENG
1
;
Xiaoli CAI
1
;
Ling LI
1
;
Jiang YUE
1
;
Zhengqun LIU
1
;
Juanping YIN
1
Author Information
1. 410006 湖南省长沙市,长沙市第四医院(湖南师范大学附属长沙医院)眼科
- Publication Type:Journal Article
- Keywords:
diabetic retinopathy;
protein kinase B;
sterol regulatory element binding protein 1;
autophagy;
rat
- From:
Recent Advances in Ophthalmology
2025;45(8):609-616
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of autophagy involving the protein kinase B/sterol regulatory element binding protein 1(Akt/SREBP-1)signaling pathway in diabetic retinopathy(DR).Methods DR rat models were estab-lished via the intraperitoneal injection of streptozotocin.Rats were randomized into control(normal rats)and DM-DR groups(DR rats).The expression of autophagy-related proteins(autophagy markers LC3-Ⅱ and LC3-Ⅰ,autophagy specific substrate p62,and autophagy-related protein Beclin1)in rat retinas was compared between the two groups.Rats were di-vided into control B(normal rats injected with 1 μL saline),DR(DR rats injected with 1 μL saline),DR+si-NC(DR rats injected with 1 μL of the negative control siRNA),and DR+si-SREBP-1 groups(DR rats injected with 1 μL of the SREBP-1 siRNA).All interventions were given 1 day before modeling and 8 weeks after modeling.Akt/SREBP-1 expression and retinal ganglion cell(RGC)survival were compared among groups.R28 rat retinal precursor cells were classified into con-trol C(normal glucose,24 h),HG(high glucose,24 h),HG+si-NC(si-NC transfection+high glucose,24 h),and HG+si-SREBP-1 groups(si-SREBP-1 transfection+high glucose,24 h).The expression of autophagy-related proteins and au-tophagosome-lysosome fusion were compared among groups.Western blot and immunofluorescence were used to examine the expression of Akt,SREBP-1 and autophagy-related proteins.Results The relative expression of Beclin1 and p62 pro-teins and the LC3-Ⅱ/Ⅰ ratio in the DM-DR group were significantly higher than those in the control group 1 and 8 weeks after modeling(all P＜0.001).Compared with the control B group,the DR group exhibited elevated SREBP-1 and reduced Akt protein levels 1 and 8 weeks after modeling(all P＜0.01).RGC counts in the DR and DR+si-NC groups were significantly lower than those in the control B group(P＜0.001).The RGC count in the DR+si-SREBP-1 group was significantly higher than that in the DR+si-NC group(P＜0.001).Compared with those in the control C group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were increased in the HG and HG+si-NC groups(all P＜0.01).Compared with those in the HG+si-NC group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were reduced in the HG+si-SREBP-1 group(all P＜0.05).The HG and HG+si-NC groups showed significantly more LC3B/LAMP1 dual-positive puncta than the control C group(P＜0.001).The HG+si-SREBP-1 group showed significantly less LC3B/LAMP1 dual-positive puncta than the HG+si-NC group(P＜0.001).Conclusion SREBP-1 knockdown enhances autophagic flux in early DR to attenuate RGC loss.Thus,the Akt/SREBP-1 axis represents a promising therapeutic target for DR.
