Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review

Abstract

Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases.

Keywords: Mediterranean diet; Nrf2; age-related macular degeneration; diabetic retinopathy; glaucoma; retinopathy.

Figure 3

Pathways and cellular alterations implicated in diseases characterized by retinopathy (DR, AMD, and glaucoma) and correlation with low MeDi adherence. Scheme representing the progressive damage and the signaling pathways implicated in retinopathy and associated with low MeDi adherence. Initially, the activation of HIF pathway is observed, leading to VEGF expression, resulting in angiogenesis and subsequent vascular damage. Then, the formation of AGEs stimulates RAGE activation and subsequent inflammation. Ultimately, chronic excessive ROS formation and oxidative stress synergically lead to mitochondrial stress and apoptosis. These pathways are implicated in promoting the risk of DR, AMG, and glaucoma (Created with BioRender.com, Licensing and Agreement number XA2769UB0O).

Figure 4

Pathways involved in maintaining a healthy retina and associated with a high adherence to the MeDi. Schematic representation of the conditions and signaling pathways that are induced by a high adherence to the MeDi and that participate in maintaining a healthy retina, lowering the risk of DR, AMD, and glaucoma. High adherence to the MeDi results in: (i) a good glycemic control and insulin response; (ii) anti-inflammatory response; (iii) good ROS homeostasis. Moreover, high adherence to the MeDi promotes: (i) reduction in the cholesterol and triglyceride levels; (ii) vegetable/fruit-derived phytoestrogens that activate the Nrf2 pathway, which activates the stress response. All these conditions and pathways induced by a high adherence to the MeDi participate in lowering the risk of DR, AMD, and glaucoma (Created with BioRender.com, Licensing and Agreement number PK2769UG6I).

Figure 5

Cellular, metabolic, and signaling alterations in diabetic retinopathy. Four main interconnected mechanisms in retinopathy are shown. Müller cells have numerous functions, including maintaining the proper functioning of the blood–retina barrier. Additionally, they are involved in regulating synaptic neurotransmission and providing neuroprotection. Finally, the most affected processes involve metabolic and genomic pathways linked to hyperglycemia, such as the polyol pathway and the activation of protein kinase C. Created in BioRender.

Figure 1

(A) The MeDi pyramid. The basis of the pyramid includes the Mediterranean lifestyle, with conviviality and daily moderate physical activity. The food categories and the frequency of consumption that represent a high adherence to the MeDi are indicated. (B) MeDi adherence. Progressive effects induced by lowering the adherence to the MeDi from high (green) to very low (red): starting from ROS production, to increased AGEs formation, followed by inflammation and finally chronic progression of retinopathy (Created with BioRender.com, Licensing and Agreement number GT2769TZYW).

Figure 2

Schematic representation of the various MeDi scoring methods. The different MeDi scoring methods are indicated together with the adherence to the MeDi from lower to higher score (Created with BioRender.com, Licensing and Agreement number SX2769U3H2) [25,26,27,28,29,30,31].