Activation of neuroprotective signalling pathways in the retina by aptamer

• Applicant: Dr. José Hurst
• Subject Area: Ophthalmology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427911931

Retinal degeneration processes, such as those occurring in age-related macular degeneration (AMD) or retinitis pigmentosa (RP), result in the death of the photoreceptors and thus lead to blindness. Growth factor-based therapy is an experimentally proven approach to slow down or halt photoreceptor degeneration. A promising neurotrophic growth factor is the brain derived neurotrophic factor (BDNF), which unfolds its effect by activating the TrκB signal cascade. By using an already published aptamer that specifically binds to the TrκB receptor, we aim to mimic the neuroprotective effect of BDNF and develop more broadly applicable treatments for retinal diseases. At the same time, it is planned to further investigate and characterize the role of individual signaling molecules involved.Our preliminary results confirmed the biocompatibility of the TrκB aptamer on primary retinal cells and in the retinal organ model. In addition, a better binding efficiency and a neuroprotective effect were demonstrated in an ex vivo degeneration model.TrκB receptor activation with an aptamer targets specifically the desired cells, is more stable than the actual ligand, and can be used in much lower concentrations. This should reduce side effects and the problem of the low half-life time, which occurred in the previous BDNF therapy approaches.The aim of this project is to evaluate the therapeutic use of the TrĸB aptamer for the treatment of multifactorial retinal degenerative diseases of photoreceptor cells such as RP and AMD and at the same time to better understand the underlying molecular pathomechanisms of these retinopathies.

• DFG Programme: Research Grants