Drug development for vision loss prevention in diseases associated with AGEs accumulation

    Gradual accumulation of glycated proteins, lipids and nucleic acid is a common process in normal aging, however an increase of oxidative stress over time triggering further protein modification and resulting in impairment of defense mechanisms. It was found that glycation plays significant role in the pathogenesis of retinal diabetic neuropathy by triggering different mechanisms resulting in neuronal dysfunction.

    In retinal apoptosis both caspase-dependent and caspase-independent cell death pathways are involved already in a presense of very low dose of AGEs. Also increased expression of transcription factor NF-kB and SP1 in AGEs exposed retinas confirms the expression of RAGE genes. That knowledge suggests that the research of precise therapeutic strategy providing neuroprotection in early stage of neurodegeneration should be established.

    Based on our previous research, the aim of our study was to invent the combined therapeutic agents with neuroprotective abilities for diabetic retinopathy and diseases associated with AGEs accumulation.

    In our talk the combination of the NT4, citicoline and TUDCA for providing the maximal neuroprotecive and regenerative effect by influencing on different pathological pathways, which are triggered in diseased associated with AGEs accumulation is presented.

    Key words: diabetic retinopathy, neuroprotection, neuroregeneration, 3d culture, retinal diseases.