Abstract
PurposeIncreased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for ‘Diabetes Vision Function’, on diabetic retinopathy.MethodsStreptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-kB.ResultsDiabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3–4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities.ConclusionsNutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.
Highlights
Retinopathy remains one of the most devastating complications of diabetes
We have shown that zeaxanthin administration in diabetic rats prevents increase in retinal oxidative stress and proinflammatory cytokines, Vascular endothelial growth factor (VEGF), Intercellular Adhesion Molecule-1 (ICAM-1) [26], and antioxidants containing vitamin C, vitamin E, β-carotene, N-acetyl cysteine and other micronutrients inhibit the development of diabetic retinopathy [4,24]
The goal of this study is to investigate the effect of the nutritional supplementation, which is in ‘Diabetes Vision Function’ clinical trials to improve the structure and function of the retina, on the development of diabetic retinopathy
Summary
Retinopathy remains one of the most devastating complications of diabetes. Retina and its capillary cells experience increased oxidative stress, and their mitochondria become dysfunctional and mitochondrial DNA (mtDNA) is. In addition to oxidative stress, the retina presents many abnormalities consistent with other inflammatory diseases, and animal models have provided promising results with anti-inflammatory therapies, suggesting that retinopathy is a low-grade chronic inflammatory disease [11,12]. Vascular endothelial growth factor (VEGF), an angiogenic factor important in vascular permeability and neovascularization, is elevated in the retina and vitreous of diabetic patients and animals, and this increase is associated with the manifestation of diabetic retinopathy [13,14,15]. Rodent models have demonstrated that the antioxidants that inhibit the development of diabetic retinopathy, inhibit increases in retinal NF-kB and IL-1β [17,18]
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