A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

Abstract

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

A Systematic Review of Carotenoids in the Management of Age-Related Macular Degeneration

“…These results may also be attributed, at least in part, to the enhanced neuroprotective capacity, afforded by these dietary antioxidants, to ameliorate pro-oxidative and pro-inflammatory mechanisms in the local tissue, particularly within the neurosensory layers of the macula [46,255,[322][323][324]. In addition to improving the total antioxidant capacity, xanthophylls may also promote metabolic efficiency of the visual transduction cascade by augmenting mitochondrial dysfunction, a primary source of intracellular free radical formation in aging retina [42,[46][47][48]255,298,324]. It has also been postulated that greater levels of carotenoids may help to promote the maintenance of synaptic network activity by enhancing cell survival and the viability of neurosensory cells [47,48,298].…”

“…In addition to improving the total antioxidant capacity, xanthophylls may also promote metabolic efficiency of the visual transduction cascade by augmenting mitochondrial dysfunction, a primary source of intracellular free radical formation in aging retina [42,[46][47][48]255,298,324]. It has also been postulated that greater levels of carotenoids may help to promote the maintenance of synaptic network activity by enhancing cell survival and the viability of neurosensory cells [47,48,298]. However, additional studies are needed to further elucidate the potential role of the carotenoids involved with synaptic network activity and cognitive function [298,325].…”

“…As a consequence of its extremely high metabolic activity and constant exposure to light, the outer retina is known to be particularly vulnerable to photo-oxidative injury and mitochondrial dysfunction, prompting the overproduction of free radical species [42][43][44][45][46]. A growing body of evidence implicates that compromised antioxidant capacity may also serve a crucial role in AMD pathology, a sequela, which occurs predominantly in response to the chronic cycles of sustained oxidative stress, paired with the concomitant depletion of endogenous antioxidants [42,43,[46][47][48]. Local inhibition of these antioxidant defense mechanisms (to counteract the accumulation of toxic byproducts and cellular debris) plays a significant role in perpetuating subsequent neurodegenerative damage onto the surrounding tissues through immunostimulatory activity [35,40,41,43,46].…”

“…The body's intrinsic homeostatic mechanisms for maintaining redox control are comprised of both exogenous and endogenous antioxidant activity for neutralizing free radical species [42,43,[46][47][48]. The mainstay of preventative nutritional therapies is aimed at the augmentation of exogenous antioxidant defenses through oral supplementation containing nutraceuticals and micronutrients.…”

Macular Pigment Reflectometry: Developing Clinical Protocols, Comparison with Heterochromatic Flicker Photometry and Individual Carotenoid Levels

“…To this accord the macular pigment optical density (MPOD) is a clinical biomarker that is altered in various disease states like age related macular degeneration [5][6][7][8][9][10][11][12][13][14][15]. The MPOD score is not only associated with many ophthalmic conditions but also with systemic Nutrients 2021, 13, 2553 2 of 17 diseases like diabetes [16,17]. The level of MPOD is also closely related to the carotenoid levels seen in the brain [18,19] making it a helpful biomarker which is associated with various cognitive functions [20][21][22][23][24][25][26][27].…”