The role of PGF-signalling in immune reactions in retinal degeneration

• Applicant: Professor Dr. Olaf Strauß, since 8/2021
• Subject Area: Ophthalmology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 447527270

Retinal degenerations with severe impact in public health, such as age-related macular degeneration or systemically-induced diseases such as hypertensive retinopathy, have in common a vascular and an inflammatory component that lead to vision loss. Treatment of the vascular component by inhibition of VEGF-A increases vision in clinical routine. So far, this treatment, however, does not directly address inflammatory component. Recent studies indicate a complex role of placental growth factor (PGF), a member of the VEGF family, in retinal degeneration that includes immune regulation in addition to well-known vascular effects. In contrast to the vascular effects, the immunregulatory effects are not well studied so far in the retina. The fact that patients resistant to anti-VEGF-A therapy show increased PGF levels in aqueous humor probes and profit by improved morphology together with longer application intervals from combined anti-VEGFA/PGF therapy with variations among clinical studies, justifies a systematic analysis of the inflammatory component in acquired retinal degeneration. We hypothesize PGF as a master regulator of retinal tissue repair in acute and chronic conditions of damage. Using in vitro and in vivo methods, we will investigate PGF-mediated mechanisms at the cellular level and in animal models of acute or chronic retinal degeneration. Focusing on the immune reaction, we will identify PGF target cells, their phenotypic changes and temporal and spatial dynamics of PGF production. In this way, we will identify the mechanisms/pathways that turn a physiological reaction into pathologic scenarios. We believe that either PGF expression that ads to immune over-reaction in acute insults, chronic low-grade inflammation due to insufficient termination of PGF expression or systemic PGF dysregulation in conjunction with local harmful influences drive physiological reactions into disease states.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Nadine Reichhart, until 7/2021