Section 1 The Eye in Diabetes

**3**

**1. Introduction**

**Chapter 1**

*and Andrew Tsin*

**Abstract**

Advanced Glycation End Products:

Formation, Role in Diabetic

retinopathy but will also explore how they impact other diseases.

diabetic retinopathy, inflammation, cytokine, neovascularization

**Keywords:** advanced glycation end products, oxoaldehyde, RAGE, hyperglycemia,

Advanced glycation end products (AGEs) are formed through a non-enzymatic

process in hyperglycemic conditions, and they impact the retinal vasculature negatively through the formation of reactive oxygen species, secretion of aberrant proteins or growth factors, alteration of the extracellular matrix, and secretion of inflammatory cytokines [1]. It is important to consider the difficulty of differentiating the effects of hyperglycemia from those of AGEs, as AGE concentration is controlled by glucose levels. Because of this, occasionally high glucose levels are

Clinical Applications

Complications, and Potential in

*Rujman Khan, Xin Yee Ooi, Matthew Parvus, Laura Valdez* 

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic

## **Chapter 1**
