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

Abstract

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.

The Modification of Detrimental Biochemical Anomalies May Reduce the Rate of Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus

“…It has been demonstrated by landmark studies that improving glycemic control reduces the risk of development and progression of DR, though there is no lower limit of glycemic control that is protective against the onset of retinopathy [15,16]. Our sequential studies have suggested that hyperglycemic and dyslipidemia-induced biochemical derangements result in tissue hypoxia and up-regulation of VEGF [17,18]. The important anomalies related to mishandling of glucose and lipids leading to increased generation of advanced glycation and lipid peroxidation end products, oxidative stress, and failure of the body's antioxidant defense systems, ultimately invite inflammation, hypoxia, and increased VEGF secretion [17,18].…”

“…Our sequential studies have suggested that hyperglycemic and dyslipidemia-induced biochemical derangements result in tissue hypoxia and up-regulation of VEGF [17,18]. The important anomalies related to mishandling of glucose and lipids leading to increased generation of advanced glycation and lipid peroxidation end products, oxidative stress, and failure of the body's antioxidant defense systems, ultimately invite inflammation, hypoxia, and increased VEGF secretion [17,18].…”

The Amelioration of Detrimental Biochemical Anomalies by Supplementing B, C, and E Vitamins in Subjects with Type 2 Diabetes Mellitus May Reduce the Rate of Development of Diabetic Retinopathy

“…It has been demonstrated by landmark studies that improving glycemic control reduces the risk of development and progression of DR, though there is no lower limit of glycemic control that is protective against the onset of retinopathy [ 15 , 16 ]. Our sequential studies have suggested that hyperglycemic and dyslipidemia-induced biochemical derangements result in tissue hypoxia and upregulation of VEGF [ 17 , 18 ]. The important anomalies related to mishandling of glucose and lipids leading to increased generation of advanced glycation and lipid peroxidation end products, oxidative stress, and failure of the body's antioxidant defense systems ultimately invite inflammation, hypoxia, and increased VEGF secretion [ 17 , 18 ].…”

“…Our sequential studies have suggested that hyperglycemic and dyslipidemia-induced biochemical derangements result in tissue hypoxia and upregulation of VEGF [ 17 , 18 ]. The important anomalies related to mishandling of glucose and lipids leading to increased generation of advanced glycation and lipid peroxidation end products, oxidative stress, and failure of the body's antioxidant defense systems ultimately invite inflammation, hypoxia, and increased VEGF secretion [ 17 , 18 ].…”

“…Our sequential studies have suggested that hyperglycemic and dyslipidemia-induced biochemical derangements result in tissue hypoxia and upregulation of VEGF [17,18]. The important anomalies related to mishandling of glucose and lipids leading to increased generation of advanced glycation and lipid peroxidation end products, oxidative stress, and failure of the body's antioxidant defense systems ultimately invite inflammation, hypoxia, and increased VEGF secretion [17,18]. This study included 185 diabetic patients who had been treated with antihyperglycemic medication along with Similarly, for one-unit increase in VEGF, the risk of DR is increased by 3.6% (95% LCL = 1:01, UCL = 1:07) and a unit increase in MDA increases the risk of DR by a factor of 7.5% (95% LCL = 0:71, UCL = 1:64).…”