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Integration of microglia in retinal organoids

2025
Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria
Infections during pregnancy can endanger the development of the baby's brain and eyes. However, knowledge about the safe use of anti-inflammatory drugs during pregnancy is still limited. Although the functional effects of viral stimulation have been studied in brain organoid models derived from human induced pluripotent stem cells (hIPSC), these models generally lack microglia, which are susceptible to and promote inflammation. In addition, microglia are actively involved in neuronal development. To investigate this in more detail, hIPSC-derived microglial cells were generated here and integrated into retinal organoids. In this model, a viral infection was mimicked and it was observed how the microglia react and interact with other cells in the retina. It was shown that the microglia release inflammatory substances during this simulated infection and stimulate cell growth in the retina. At the same time, the effect of the anti-inflammatory drug ibuprofen was investigated. It was able to attenuate some of the changes triggered by the simulated infection. Of particular note was that ibuprofen was able to normalize the activity of certain nerve cells in the retina - but this only occurred when microglia were present. These findings highlight the importance of microglia in responding to infection during development and provide insights into the mechanisms by which ibuprofen may exert protective effects. It appears that ibuprofen exerts its effect by influencing certain enzymes that are active in both microglia and other cells of the retina.
Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids
Sandra Siegert
#2174
Added on: 04-29-2025
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