The regulation of these aforementioned transcription factors are done by i.a. In diabetes-due to over-transactivation by dysregulated transcription factors (NF-kappaB, PARP1 etc.)-excess levels of MMP9 transported into the mitochondria may lead to mitochondrial damage. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.įormerly BGP-15 was demonstrated to induce heat shock protein (HSP) 72, a cytosolic protein belonging to the HSP 60/70 kDa family responsible for e.g., the transport of matrix metalloproteinase 9 (MMP9) into the mitochondria. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The used methods include weight measurement, glucose-related measurements-like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results-electroretinography and Western Blot. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG).

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