Advanced glycation end product crosslinks in lens crystallins (AGE-crystallin crosslinks)

Advanced glycation end product (AGE) crosslinks in long-lived lens proteins, specifically crystallins, are permanent post-translational modifications that accumulate over a lifetime due to the lack of protein turnover in the ocular lens (Lynnerup et al., 2008). These crosslinks result from the non-enzymatic Maillard reaction between reducing sugars or reactive dicarbonyls and the amino groups of proteins, leading to the formation of complex, often fluorescent, covalent structures like pentosidine and glucosepane (Serebryany et al., 2016). The accumulation of these AGEs causes crystallins to aggregate into high-molecular-weight complexes, which scatter light and reduce lens transparency, eventually manifesting as cataracts (Kessel et al., 2021). Furthermore, AGE-induced crosslinking increases the stiffness of the lens, contributing to presbyopia, the age-related loss of accommodative power. Therapeutic interventions focus on AGE breakers designed to chemically cleave established crosslinks or inhibitors that prevent their formation by scavenging reactive intermediates (Gasser et al., 2011). Targeting these crosslinks represents a pharmacological approach to restoring lens function and potentially delaying or reversing the need for surgical cataract extraction.

Other names

AGE-modified lens proteinsGlycation-induced protein aggregatesMaillard reaction products in lensCrystallin advanced glycation end productsLens protein crosslinks

Therapeutic agents act as AGE breakers by chemically cleaving established alpha-diketone covalent crosslinks or as AGE inhibitors by scavenging reactive dicarbonyl intermediates (e.g., methylglyoxal) to prevent the formation of new crosslinks (Gasser et al., 2011; Kessel et al., 2021).