POTENTIAL THERAPEUTIC BENEFITS OF SPERMINE OXIDASE INHIBITION IN ISCHEMIC RETINOPATHY: EXPERIMENTAL EVIDENCE

Abstract

Polyamines have crucial roles in cell processes like growth, differentiation, and proliferation. Disruptions in polyamine metabolism impact central nervous system disorders, including brain injury and cerebral ischemia. Studies from our laboratory highlighted the involvement of polyamine oxidation in retinal diseases, showing elevated spermine oxidase (SMOX) levels in inner retinal neurons. In a prior study, MDL 72527, an SMOX inhibitor, protected against retinal vaso-obliteration and neovascularization in an oxygen-induced retinopathy (OIR) model. However, the underlying molecular mechanisms remain unclear. Our investigation focused on investigating the molecular mechanisms of MDL 72527-mediated vasoprotection in the OIR retina. Results revealed that SMOX inhibition downregulated microglia/macrophage populations, reduced VEGF and Claudin 5 expression, suppressed acrolein-conjugated protein levels, and downregulated P38/ERK1/2/STAT3 signaling in the OIR retina. Additionally, BSA-Acrolein conjugates reduced viability of human retinal endothelial cells (HRECs) and activated P38 signaling. These findings shed light on the therapeutic potential of SMOX inhibition in ischemic retinopathy conditions.