Zinc Nutrition and Inflammation in the Aging Retina

Abstract

Zinc is an essential nutrient for human health. It plays key roles in maintaining protein structure and stability, serves as catalytic factor for many enzymes, and regulates diverse fundamental cellular processes. Zinc is important in affecting signal transduction and, in particular, in the development and integrity of the immune system, where it affects both innate and adaptive immune responses. The eye, especially the retina‐choroid complex, has an unusually high concentration of zinc compared to other tissues. The highest amount of zinc is concentrated in the retinal pigment epithelium (RPE) (RPE‐choroid, 292 ± 98.5 µg g−1 dry tissue), followed by the retina (123±62.2 µg g−1 dry tissue). The interplay between zinc and inflammation has been explored in other parts of the body but, so far, has not been extensively researched in the eye. Several lines of evidence suggest that ocular zinc concentration decreases with age, especially in the context of age‐related disease. Thus, a hypothesis that retinal function could be modulated by zinc nutrition is proposed, and subsequently trialled clinically. In this review, the distribution and the potential role of zinc in the retina‐choroid complex is outlined, especially in relation to inflammation and immunity, and the clinical studies to date are summarized.

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

“…Most of the intracellular zinc is tightly bound, compartmentalized, and sequestered with high affinity by proteins, including metallothioneins (MTs), facilitating specific processes. As a consequence of these high-affinity binding events, the concentration of available zinc, referred to as “free,” “labile,” “mobile,” or “exchangeable” zinc, for metabolic processes is tightly regulated ( Gilbert et al, 2019 ). Upon perturbation, cytosolic zinc metalloproteins respond to transient cytosolic zinc ion concentration changes, which is termed “zinc muffling” ( Tuncay et al, 2019 ).…”

Nerve Growth Factor-Based Therapy in Alzheimer’s Disease and Age-Related Macular Degeneration

“…Consistent with previous evidence ( Micera et al, 2019 ), new findings show that Cu is increased in choroid-RPE of AMD. In contrast to Fe and Cu trends, Zn appears decreased in the aged retina and Zn supplementation has been proposed for AMD treatment ( Gilbert et al, 2019 ). Zn supplementation has beneficial effects in reducing the progression of AMD according to the Age-Related Eye Disease Study (AREDS; Age-Related Eye Disease Study Research Group (AREDSRG), 2000 ; Chew et al, 2015 ; Seddon et al, 2016 ): daily supplementation with a formulation consisting of 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc, 2 mg copper, 10 mg lutein, and 2 mg zeaxanthin (AREDS and AREDS2) was effective for slowing AMD progression ( Kim et al, 2016 ).…”

Zinc as a modulator of transglutaminase activity – Laboratory and pathophysiological aspects

“…After iron, zinc is the most abundant transition metal in man and is found in body fluids and in the nuclei, cytoplasm and membrane of all cells in the body. About 90% of the total 2–3 g are found in the skin, skeletal and muscles, while the highest concentrations have been reported in the prostate gland [ 2 ], retina [ 3 ], and the insulin-producing β-cells [ 4 ]. Zinc is bound to numerous proteins with varying affinities [ 5 ].…”