The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration

Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes are attributed to the aging process. The nature of the aging process has been the subject of considerable speculation. Accumulating evidence now indicates that the sum of the deleterious free radical reactions going on continuously throughout the cells and tissues constitutes the aging process or is a major contributor to it. In mammalian systems the free radical reactions are largely those involving oxygen. Dietary manipulations expected to lower the rate of production of free radical reaction damage have been shown (i) to increase the life span of mice, rats, fruit flies, nematodes, and rotifers, as well as the "life span" of neurospora; (ii) to inhibit development of some forms of cancer; (iii) to enhance humoral and cell-mediated immune responses; and (iv) to slow development of amyloidosis and the autoimmune disorders of NZB and NZB/NZW mice. In addition, studies strongly suggest that free radical reactions play a significant role in the deterioration of the cardiovascular and central nervous systems with age. The free radical theory of aging provides reasonable explanations for age-associated phenomena, including (i) the relationship of the average life spans of mammalian species to their basal metabolic rates, (ii) the clustering of degenerative diseases in the terminal part of the life span, (iii) the beneficial effect of food restriction on life span, (iv) the greater longevity of females, and (v) the increase in autoimmune manifestations with age. It is not unreasonable to expect on the basis of present data that the healthy life span can be increased by 5-10 or more years by keeping body weight down, at a level compatible with a sense of well-being, while ingesting diets adequate in essential nutrients but designed to minimize random free radical reactions in the body.

https://www.pnas.org/content/pnas/78/11/7124.full.pdf

The aging process

The discovery of the adventitious formation of the potential cancer-causing agent acrylamide in a variety of foods during cooking has raised much concern, but the chemical mechanism(s) governing its production are unclear. Here we show that acrylamide can be released by the thermal treatment of certain amino acids (asparagine, for example), particularly in combination with reducing sugars, and of early Maillard reaction products (N-glycosides). Our findings indicate that the Maillard-driven generation of flavour and colour in thermally processed foods can -- under particular conditions -- be linked to the formation of acrylamide.

Acrylamide from Maillard reaction products

Lyophilization and development of solid protein pharmaceuticals

Publisher Summary Aberrant glycosylation is the most common phenomenon associated with oncogenic transformation expressed in cell membranes of animal and human cancer cells. Such aberrant structures at the surface membranes may well be effective targets in prevention, diagnosis, and treatment of human cancer. Many of the aberrant glycosylation products can be recognized by specific MAbs as tumor-associated carbohydrate antigens. Many of these antigens have been identified as carbohydrates, thus there is increasing evidence that essentially all human cancers are characterized by aberrant glycosylation. Aberrant glycosylation as such may be the basis of inappropriate cell/cell and cell/matrix interactions that may be reflected in the abnormal cell social behavior of tumor cells, such as uncontrolled cell growth, invasiveness, and metastatic potential. Whatever the genetic or epigenetic basis of expression of aberrant glycosylation is, the phenomenon is of crucial importance in understanding the antisocial behavior of tumor cells as well as in practical applications in diagnosis and treatment of human cancer.

Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens

The Carbohydrates: Chemistry and Biochemistry

Purification and characterization of bovine and ovine submaxillary mucins.

Serine and threonine glycosidic linkages in bovine submaxillary mucin.

The isolation and characterization of rat sublingual mucus-glycoprotein.

Hyaluronic acid, a linear polymer of alternating N-acetyl-D-glucosamine and D-glucuronic acid units with a molecular weight of 105 to 107, is known to be degraded by X-rays, ultraviolet radiation, and ultrasonic waves (1-6). This substance and other natural and synthetic polymers are also degraded by autoxidants such as ascorbic acid or ferrous or cuprous ions in the presence of oxygen (7), by mechanisms probably involving free radicals (5, 8, 9) similar to those involved in their degradation by radiations. This latter reaction has been described as the oxidativereductive depolymerization (ORD) reaction (10). Alexander et al. (8, 11) noted degradations of polymethacrylic acid by both X-rays and several autoxidants such as cysteine, but the present study is the first formal comparison of the effects of radiations and autoxidants on hyaluronic acid. The present work was carried out in order to compare the effects of radiation on hyaluronic acid with those produced by autoxidants under closely similar conditions. A semiquantitative comparison of the effects of X-rays, ,B-rays (P32, internally), and autoxidants is reported. The effect of visible light with riboflavin as sensitizer was also studied. For the ORD reaction, the results of a survey of possible autoxidants and antioxidants are included. Viscometric measurements were used as the criterion of the degree of degradation of hyaluronic acid.

Ward Pigman

Papers

The Carbohydrates: Chemistry and Biochemistry

Purification and characterization of bovine and ovine submaxillary mucins.

Serine and threonine glycosidic linkages in bovine submaxillary mucin.

The isolation and characterization of rat sublingual mucus-glycoprotein.

Depolymerization of Hyaluronic Acid by Autoxidants and Radiations