The advanced glycation end product (AGE)–RAGE axis has been implicated in the pathophysiology of diabetic bladder dysfunction (DBD). However, no previous studies have explored the effects of RAGE blockade on this condition. Here, we explored the effects of the selective RAGE inhibitor TTP488 (azeliragon) at the functional and molecular levels of bladder dysfunction in ob/ob leptin-deficient mice. Female B6.V-Lep ob/JUnib (ob/ob) and wild-type (WT) C57BL/6 mice were used as lean controls. Treatment with TTP488 in ob/ob mice resulted in no changes in body weight, fasting glucose, or insulin resistance; however, it reduced total AGE and MG-H1 levels without altering RAGE levels in bladder tissues. TTP488 normalized glyoxalase-1, glutathione reductase, glutathione peroxidase, and superoxide dismutase activities in bladder tissues. Marked increases in collagen intensity were also observed in ob/ob mice, an effect fully reversed by TTP488 treatment. TTP488 reduced total void volume, volume per void, and ex vivo bladder contractility in response to electrical-field stimulation and carbachol. Our finding that TTP488 mitigates DBD in ob/ob mice supports the proposal that RAGE blockade could serve as a promising therapeutic strategy for managing DBD.

The aim of this article is to introduce the concepts of nonlinear optical microscopy using only undergraduate-level physics and mathematics, based on the harmonic oscillator differential equation and Euler ’ s formula ( e i θ ) . We also provide supplementary laboratory videos illustrating these phenomena, together with application examples from our laboratory. We first discuss dipole radiation and resonance effects and then introduce second- and third-harmonic generation, sum- and difference-frequency generation, and coherent anti-Stokes Raman scattering. Throughout the article, we use the simple one-dimensional Lorentz forced harmonic oscillator model, which provides an intuitive and physically meaningful framework for describing resonant absorption in dielectric media and molecules. Finally, we presented highlights of some of our results and discuss several applications of non-linear optics microscopies in lifesciences.