scholarly journals Role of Lipid, Protein-Derived Toxic Molecules, and Deficiency of Antioxidants behind the Pathogenesis of Diabetic Retinopathy (DR) in Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Subhasish Pramanik ◽  
Lakshmi Kanta Mondal ◽  
Subhankar Chowdhury ◽  
Chiranjit Bose ◽  
Debgopal Bera ◽  
...  

To determine the role of NADPH-oxidase mediated formation of different lipid, protein-derived molecules, and depletion of vitamin-C level in vitreous behind the endothelial dysfunction-induced vascular endothelial growth factor secretion and pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fourteen T2DM patients with mild non-proliferative diabetic retinopathy (MNPDR), 11 patients without diabetic retinopathy (DNR), 17 T2 DM subjects with high-risk proliferative diabetic retinopathy (HRPDR), and 5 healthy individuals without DM underwent vitreous analysis for estimation NADPH oxidase, lipid peroxide like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE) and advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY), protein carbonyl compound (PCC), Vitamin-C and concentration of vascular endothelial growth factor (VEGF) secretion following standard spectrophotometric methods and enzyme-linked immunosorbent assay (ELISA). Vitreous concentration of NADPH-oxidase, different protein and lipid-derived molecule, and VEGF were found to be significantly elevated among DNR and of DR subjects with different grades compared to HC subjects whereasthe vitamin-C level was found to be decreased among different DR subjects and DNR subjects in comparison to healthy individuals. Oxidative stress-mediated lipid and protein-derived biomolecules not only add important mediators in the pathogenesis of DR, but also accelerate the progression and severity of microangiopathy.

2019 ◽  
Vol 19 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Jana Sajovic ◽  
Ines Cilenšek ◽  
Sara Mankoč ◽  
Špela Tajnšek ◽  
Tanja Kunej ◽  
...  

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several VEGF-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between VEGF-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of >10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 – 2.86, p = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR.


2020 ◽  
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed

Abstract Background: The incidence of type 2 diabetes mellitus (T2DM) is rising in working age adults in Pakistan. Diabetic patients have a greater chance for developing diabetic retinopathy (DR). There is negligible research on the genetic factors contributing to DR in Pakistani population. This study was done to investigate the association of vascular endothelial growth factor A gene (VEGFA) polymorphisms, 2578 C/A (rs699947) and 1154 G/A (rs1570360) with T2DM, diabetic retinopathy and serum VEGF levels in Pakistani patients. Methods: A case-control study, conducted from Jan 2017 to Dec 2018, including 450 subjects: 150 DR, 150 diabetics without retinopathy (DWR) and 150 healthy controls (HC). Genotyping was done by ARMS-PCR and serum VEGF levels were measured by ELISA. Descriptive and inferential statistics were calculated to compare genotypic / allelic frequencies and biochemical variables. Results: No statistically significant association of rs699947 and rs1570360 genotypic and allelic frequencies were found with DR as compared to DWR. The rs699947 heterozygosity was associated with DWR and homozygous mutant allele A with DWR and DR as compared to HC. Upon stratifying DR into non- proliferative (NPDR) and proliferative (PDR) sub- types, rs699947 AA genotype was significantly associated with PDR as compared to DWR in univariate and multinomial regression analysis. In allelic, dominant and recessive models, the minor allele A showed significant association with DWR and DR as compared to HC. Significantly raised serum VEGF levels were found in DR patients as compared to DWR and were associated with rs699947 and rs1570360 heterozygosity in DWR. Serum VEGF showed a positive correlation with fasting plasma glucose (FPG), cholesterol and LDL-C in DR and DWR groups. rs699947 genotype showed significant association with DWR and DR in Punjabi and Pathan and with DR in Kashmiri ethnic groups compared to HC. rs1570360 was significantly association with DR as compared to DWR in Kashmiri ethnic group. Conclusion: Our study endorses the role of VEGF 2578C/A (rs699947) gene polymorphism in the pathogenesis of T2DM and proliferative diabetic retinopathy in Pakistani patients. Serum VEGF levels have a positive correlation with T2DM and severity of DR.


Author(s):  
Nermien Abd El Rahman Ibraheim ◽  
Fatema El Zahraa Sayed Bukhary ◽  
Yehia Zakareia Mahmoud ◽  
Mahmoud Ragab Mohamed ◽  
Salama Rabei Abdel-Rahim

Sign in / Sign up

Export Citation Format

Share Document