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Abstract
Polyamines play significant roles in cellular processes such as cell growth, differentiation, and proliferation. Disruptions in polyamine metabolism have been implicated in various central nervous system disorders, including brain injury and cerebral ischemia. Studies from our laboratory have demonstrated the critical involvement of polyamine oxidation in retinal disease models with elevated spermine oxidase (SMOX) levels in inner retinal neurons. A previous study has indicated that SMOX inhibition using MDL 72527 protected against retinal vaso-obliteration and neovascularization in an experimental model of oxygen-induced retinopathy (OIR). However, the underlying molecular mechanisms are not completely studied. In the present study, we investigated the mechanisms of MDL 72527-mediated vasoprotection in the OIR retina. Our results show that SMOX inhibition using MDL 72527 downregulated microglia/macrophage population, reduced the expression of VEGF and Claudin 5, suppressed acrolein-conjugated protein levels, and the downregulation of P38/ERK1/2/STAT3 signaling in the OIR retina. Further, we demonstrated that treatment with BSA-Acrolein conjugates significantly reduced the viability of human retinal endothelial cells (HRECs) and activated P38 signaling. These findings provide valuable insights into the potential therapeutic benefits of SMOX inhibition in ischemic retinopathy.