TAS1R3 stimulation in the retina: exploring new molecular pathways in eye diseases

• Applicants: Professor Dr. Olaf Strauß; Professor Dr. Oliver Zeitz
• Subject Area: Ophthalmology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578260990

Progress has been made in the treatment neovascular age-related macular degeneration (nAMD and AMD respectively), yet the condition still belongs to the most important causes of blindness in Europe. The backbone of the current gold standard treatment is VEGF-A inhibition. Yet, the treatment response is highly variable and poorly predictable resulting in a broad range of outcomes. This strongly suggests that so far unidentified factors other than VEGF-A and some closely related pathways are involved in the pathophysiology of nAMD. Inflammation, apoptosis and angiogenesis constitute the key mechanisms of AMD, all of which are mechanisms not specific to the eye. Hence, we hypothesize overarchingly that the course of AMD is influenced by extraocular factors. In our previous work, we could show that systemic levels of saccharin correlates inversely with the severity of treated nAMD in patients. In a back translation approach, we have identified that the sweet receptor TAS1R3 is expressed in the retina. Stimulation of TAS1R3 in animal models for nAMD exerted comparable effects like in clinic. We hypothesize that saccharin acts through the taste receptor TAS1R3 at the retinal pigment epithelium (RPE) that forms the outer blood/retina barrier. Preliminary data support this assumption. Within the proposed project, we aim at getting deeper insights into how TAS1R3 modulates angiogenesis and inflammation in the retina. There are hints in preliminary data, that not only the RPE expresses TAS1R3 yet also microglial cells and other retinal cell types. We would like to understand the intracellular signaling of TAS1R3 in various retinal cell types to get insights into potential effects of TAS1R3 stimulation and to identify potential targets downstream of the receptor. While our preliminary data strongly support a role of TAS1R3 in modulating activity of nAMD, there could also be an impact in other retinal diseases. Therefore, we investigate the impact of TAS1R3 stimulation in a model of chronic retinal inflammation mimicking features of atrophic AMD. In addition, retinal vein occlusions. Finally, we aim at expanding the clinical data base by analyzing blood samples from a nutritional study from the Berlin Macula Registry. Overall, we propose characterization of the sweet receptor TAS1R3 in the retina. The assumptions behind this proposal are backed-up well be preliminary data. The proposed program will reveal add information on a so far unconsidered mechanism to the understanding of nAMD. Thereby, it will contribute to an expansion of the target space for AMD and potentially beyond.

• DFG Programme: Research Grants