Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage

Abstract

Background: Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the receptor for AGEs (RAGE) pathway. Conclusions: This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.

Keywords: ER stress; autophagy; diabetic retinopathy; glyoxalase; inflammation; methylglyoxal; oxidative stress.

Figure 1

Schematic representation of methylglyoxal’s sources and cellular outcomes.

Figure 2

Roles of CD40 activation and Müller cell–microglia communication in MGO-induced chronic inflammation and promotion of new blood vessel formation in the retina.

Figure 3

Representation of MGO-induced pathways in RPE cells.

Figure 4

Role of the glyoxalase system in MGO detoxification.