Evaluation of Relevance between Advanced Glycation End Products and Diabetic Retinopathy Stages Using Skin Autofluorescence

Abstract

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.

Light and Autofluorescence, Multitasking Features in Living Organisms

“…In this section attention is paid prevalently to the biomolecules acting as endogenous fluorophores and to their possible pathophysiological meaning, rather than on the almost countless clinical optically based diagnostic applications described in dedicated papers and reviews [264][265][266][267][268][269][270][271][272][273].…”

The role of lipopolysaccharides in diabetic retinopathy

“…In addition, the interaction with its receptor contributes to the erroneous activation of multiple proinflammatory and proangiogenic pathways [ 36 ]. Of note, a recent study reported the clinical use of skin autofluorescence to assess AGE accumulation, which can serve as a non-invasive and reliable biomarker for identifying the patients at risk of sight-threatening DR [ 37 ].…”

“…Repeated intraperitoneal injections of low-dose LPS gave rise to pathological manifestations mimicking DR in healthy mice, including activation, proliferation, and migration of retinal microglia; infiltration of the retina by monocyte-derived macrophages; and the highly reproducible breakdown of the BRB accompanied by subretinal fluid accumulation [ 52 ]. In parallel, systemic administration of low-dose LPS caused a 3.5-fold increase in endothelial cell injury and thinning (10-13 µm) of the posterior retina in diabetic mice [ 53 ], further deterioration of neural function, augmented loss of photoreceptors, worsening of synaptic connectivity, and an increased number of activated microglia in P23H rats (a retinal neurodegenerative animal model) [ 37 – 39 , 54 ].…”

Advanced Glycations End Products in the Skin as Biomarkers of Cardiovascular Risk in Type 2 Diabetes

“…Some studies reported a lack of association between DR and skin AGEs [ 36 , 52 ]. However, most recent studies have found a clear independent correlation with development of retinopathy and its severity [ 38 , 46 , 53 , 54 , 55 ]. Interestingly, Takayanagi et al [ 55 ] demonstrated that skin AGEs are not only related with the presence and severity of DR but also with the progression of DR.…”