Figure 9.

Sustained depletion of retinal microglia is associated with synaptic degeneration and atrophy. A, Synaptic ultrastructure in the OPL as revealed by transmission electron microscopy demonstrated normal presynaptic termini structures (black *) in both WT and TG control retinas, but the frequent presence of irregularly shaped termini with electron-dense, osmiophilic cytoplasm with thickened and irregular ribbons in the TG-depleted retina (red *), indicative of synaptic degeneration; magnified view of degenerating synapses shown in insets. B, Quantitative analysis demonstrates that in microglia-depleted retinas, OPL termini density was similar to WT and nondepleted TG controls (left). However, analysis of the fraction of OPL termini with electron-dense cytoplasm (right) showed a general increase in the proportion of degenerating termini with electron-dense cytoplasm in microglia-depleted retina (data are represented as mean ± SEM; p values reported for one-way ANOVA with multiple comparisons, n = 3 female, 8-week-old animals per group and 13 imaging fields per condition). C, Synaptic ultrastructure in the IPL demonstrated altered distribution of synaptic vesicles surrounding the ribbons (highlighted in circles) of rod bipolar cells (RBCs). Postsynaptically, the dendrites of amacrine cells (ACs) showed increased vacuolation (arrow) and mitochondrial swelling (arrowhead). Scale bars, 1 μm.