Trisomy 21 (T21), also known as Down syndrome, is a disorder in which an individual has a third copy of the 21st chromosome. This genetic disorder causes mental and physical, and developmental deficits depending on the individual. In our project, we are using retinal tissue to study the differences in morphology, location, and number of immune cells in fetal tissue samples with trisomy 21 versus those without. It has been observed that increased cytokine (signaling molecule) levels in mice with trisomy 21 interfere with certain signaling in the hippocampus of the brain. Another trend is the spine density being lower in trisomy 21 mice, which ultimately decreases neuron activity in the hippocampus as well. Microglia, which are the immune cells of the brain and eyes, behave differently and reside in different areas pertaining to the retina specifically. Overall, the cognitive deficits in trisomy 21 mice could be due to the microglial dysregulation that has been previously observed. More importantly, we want to focus on the idea that hyperactive microglia can cause alterations in the function of certain neuronal circuits, leading to the observed effects of trisomy 21. As a preliminary experiment, we stained and imaged whole retinal spheres from human fetal retinas and found the number of microglia yielded no significant difference between T21 samples and control samples. However, we found that the T21 microglia looked much larger and resided in different areas of the retinal tissue than the controls. We will observe these differences further through staining and identifying the activation level of microglia by morphology in the retinas of T21 versus control fetal tissue.