Indoleamine 2,3-dioxygenase: Antioxidant enzyme in the human eye

Abstract

Free tryptophan is degradated in the human eye by IDO, an antioxidative enzyme. IDO may be an antioxidant mechanism in the eye.

Decreased protein nitration in macrophages that overexpress indoleamine 2, 3-dioxygenase

“…While our data do not show a direct cause and effect relationship between IDO activity and oxidative damage, our results are consistent with the postulate that IDO activity may have an antioxidant function [11,[25][26][27]. IDO activity could mitigate oxidative damage by multiple mechanisms: (1) consuming superoxide anions [68,69], which should limit the formation of other ROS; (2) generating downstream products, including 3-hydroxykynurenine and 3-hydroxyanthranilic acid, which are free radical scavengers [11,26,70,71]; (3) increasing cellular NAD levels, which indirectly helps to maintain cell viability [72,73]. RAW 264.7 macrophages probably possess the enzymes required make 3-hydroxykynurenine, 3-hydroxyanthranilic acid and NAD [73,74]; therefore, we cannot dismiss the potential contribution of those molecules to the apparent antioxidant effect of IDO.…”

“…1.13.11.42) catalyzes the oxidative cleavage of the essential amino acid tryptophan; the reaction product is N-formylkynurenine, which enzymatically or spontaneously converts to kynurenine [1,2]. IDO is a cytosolic, heme-containing, interferon-γ-inducible enzyme that is present in various mammalian tissues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]; however, the physiological function of IDO is not entirely known, except for the function of IDO in the context of host response to pathogens. During infection, cytokineinduced IDO activity [5,16] depletes tryptophan and forms toxic products, which are proposed to limit the proliferation of invading bacterial [16][17][18][19][20] and viral [21,22] pathogens.…”

“…Our research emphasis encompasses the biological roles and potential therapeutic implications of antigen presenting cell (APC) IDO activity on inhibiting T-cell proliferation [23,24]. In parallel, we became interested in a possible antioxidant function of IDO [11,[25][26][27]; IDO activity requires and consumes (scavenges) superoxide anions [1,[28][29][30][31][32]. Certainly, enzymes that degrade (remove) superoxide anions are fundamental antioxidant defenses, since superoxide anions are requisite precursors for other reactive oxygen species (ROS) including hydrogen peroxide, peroxynitrite, and hydroxyl radicals (see Fig.…”

“…Hence, identifying the diverse cellular mechanisms that limit ROS production and decrease oxidative stress is fundamental to designing therapeutic interventions to treat or prevent diseases that exhibit oxidative stress. We postulate that modulation of IDO activity could be a determining factor in the diverse array of diseases that exhibit oxidative stress, if a physiological role of IDO is to scavenge superoxide anions [11,[25][26][27], thereby decreasing ROS formation and oxidative damage. We began to investigate that postulate using the experiments presented in this report: (1) generate a macrophage cell line that is stably transfected with a functional IDO expression vector, and (2) determine whether over-expression of IDO mitigates superoxide anion-dependent oxidative damage to cellular proteins in vitro.…”

Immunological aspect of the liver and metastatic uveal melanoma

“…Anatomical constraints to the development of an immune response in the eye include the absence of lymphatics that limit the traffic of immune cells to the eye. Immune cells that enter the eye encounter immunosuppressive factors such as transforming growth factor beta (TGF-β), α-melanocyte stimulating hormone (MSH), retinoic acid (RA), and indoleamine 2, 3-dioxygenase (IDO) [6] . These factors suppress T cell proliferation and effector function, and could induce immunosuppressive regulatory T (Treg) cells.…”