advertisement
Editors Selection IGR 10-3
Basic research: AGE & RAGE
Comment by Rosario Hernandez on:
16959 Accelerated aging in glaucoma: immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head, Tezel G; Luo C; Yang X, Investigative Ophthalmology and Visual Science, 2007; 48: 1201-1211
Glycation is a major cause of spontaneous damage to proteins in most physiological systems. Protein damage by the formation of advanced glycation products (AGEs) occurs in lysine side chains, N-terminal amino groups, arginine and cysteine residues. AGE-modified proteins may undergo cellular proteolysis leading to the formation and elimination of glycation free adducts. Aging human tissues accumulate AGEs in an age-dependent manner and contribute to age-related functional changes in many organs such as the heart and the brain. In the diabetic retina, reactive oxygen species (ROS) are formed by AGEs in the vasculature leading to oxidative stress. This has been suggested to be a possible cause of endothelial dysfunction and loss of pericytes through apoptosis.
In this study by Tezel et al. (73) immunohistochemistry showed that AGEs are present mainly in retinal ganglion cells (RGC) and Muller cells in the glaucomatous retina; and in astrocytes and ECM in the optic nerve head. In contrast, the receptor for AGE, RAGE was found mainly in Muller cells in the retina and to a lesser degree in RGCs and astrocytes. The selective presence of RAGE in Muller cells suggests that this cell type may be able to clear AGE-modified proteins. Accumulation of AGEs in glial cells and in the extracellular space may cause activation of astrocytes and microglia to produce neurodestructive cytokines such as TNF, oxidative stress through nitric oxide (NO), inappropriate activation of signaling cascades and eventually RGC apoptosis. In addition, pathologic accumulation of AGEs in glaucomatous tissues can lead to cellular activation by AGE-modified proteins interactions with cell surface receptors, disruption of protein-protein and enzyme-substrate interactions by AGE residue formation, and increasing resistance to proteolysis of ECM proteins.
Comments
The comment section on the IGR website is restricted to WGA#One members only. Please log-in through your WGA#One account to continue.Log-in through WGA#One