Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy

Abstract

METHODS.Retinal tissues were retrieved from postmortem human eyes, including 19 individuals without diabetes, 20 with diabetes but without DR, and 20 with diabetes and DR, for lipidomic study. In a parallel study, serum samples from 28 American Indians with type 2 diabetes from the Gila River Indian Community, including 12 without DR, 7 with mild nonproliferative DR (NPDR), and 9 with moderate NPDR, were selected. A mass-spectrometry-based lipidomic platform was used to measure serum and tissue lipids. RESULTS.In the postmortem retinas, we found a graded decrease of long-chain acylcarnitines and longer-chain fatty acid ester of hydroxyl fatty acids, diacylglycerols, triacylglycerols, phosphatidylcholines, and ceramide(NS) in central retina from individuals with no diabetes to those with diabetes with DR. The American Indians' sera also exhibited a graded decrease in circulating long-chain acylcarnitines and a graded increase in the intermediate-length saturated and monounsaturated triacylglycerols from no DR to moderate NPDR.CONCLUSION. These findings suggest diminished synthesis of complex lipids and impaired mitochondrial β-oxidation of fatty acids in retinal DR, with parallel changes in circulating lipids. TRIAL REGISTRATION. ClinicalTrials.gov NCT00340678.

Serum lipidomic determinants of human diabetic neuropathy in type 2 diabetes

“…We have also reported lipidomic analyses of other diabetic complications in the Pimas, including nephropathy 13 and retinopathy. 34 The neuropathy lipidomic signatures from the current study were distinct to both the DKD and the retinopathy signatures, although signatures in all three diabetic complications centered around impaired β‐oxidation. This aligns with our mouse data of tissue‐specific metabolic and lipidomic differences in nerve, kidney, and retina in type 2 diabetes.…”

“…The Pima Indian type 2 diabetes cohort is long‐established and very homogenous and has been deeply phenotyped for several diabetic complications. 13 , 28 , 34 The great extent of homogeneity minimizes potential confounders, creating a unique opportunity to explore the biology of neuropathy in a type 2 diabetes cohort. Physical examinations and data collection followed well‐specified research protocols, resulting in high‐quality data.…”

Diabetic retinopathy: Involved cells, biomarkers, and treatments

“…The metabolic disturbances induced by DR are mainly related to metabolism of glycolysis, polyols, tricarboxylic acid, amino acids, the urea cycle, and lipids ( Xuan et al, 2020 ). Several observational studies have shown that dyslipidemia, mitochondrial apoptosis, and oxidative stress may be the predominant pathological changes of DR ( Miller et al, 2020 ; Fort et al, 2021 ; Lin et al, 2021 ; Rao et al, 2021 ). Vascular endothelial growth factor (VEGF), HbA1c, low-density lipoprotein cholesterol, myeloperoxidase, and advanced glycation end products (AGEs) are pathogenic factors of DR.…”

Relationship Between Acylcarnitine and the Risk of Retinopathy in Type 2 Diabetes Mellitus

“…In Fort PE et al.’s study, AC was detected in human retinal tissue and plasma samples. It was found that the abundance of ACs with carbon atom number ≥ 14 decreased in a gradient with the disease state of the subjects (without diabetes, diabetes without DR, and DR) ( 39 ). This finding suggested impaired mitochondrial β-oxidation of retinal FAs in the retina in DR which was consistent with our research.…”