2nd Place Co- Winner: Megan Goyal – C. Frank Webber Prize Competition
ABSTRACT
Trogocytosis of Neurons and Glial Cells by Microglial Cells in a Normal Adult Macaque Retina
| MEGAN GOYAL | McGovern Medical School at UTHealth |
Class of 2025 |
| Sponsored by: | David W. Marshak, PhD, Department of Neurobiology & Anatomy |
| Supported by: | National Eye Institute: Linking retinal circuits to perception (R01EY027859) |
| Key Words: | Microglia, Trogocytosis, Retina, Vision, Neurons |
Introduction: Microglial cells are the sole resident immune cells in the retina. The morphology of the microglia depends on their functional state. In their active state, their processes are retracted, and they have an amoeboid appearance. These amoeboid microglia migrate to the site of injuries, produce pro-inflammatory cytokines, act as macrophages and promote inflammation and apoptosis. There have been many studies of the roles of these active microglia in neurodegenerative and ocular diseases (Fan et al., 2022). Less is known about the functions of retinal microglia in their inactive state, where they have extensive processes that move continually. During development, these ramified microglia are involved in apoptosis of dying neurons and synaptic remodeling. In the brain, the mechanism underlying this pruning of synaptic connections is trogocytosis, the transfer of small pieces from neurons to microglia. This surveillance continues in adult brains, maintaining the normal structure and functions of neurons and other glial cells (Verkhratsky et al., 2021). Here we aim to identify the neurons and glial cells that undergo trogocytosis by microglial cells in the retina of a normal macaque.
Methods: We utilized a volume of serial sections of central adult male macaque retina in which many neurons that ramify in the inner plexiform layer (IPL) had been annotated previously. To identify the microglia, we surveyed the IPL and identified the somas of microglia by their small size and scant cytoplasm. We then reconstructed the microglia and studied their interactions. When a microglial cell engulfed a small piece of a neuron or glial cell and a lysosome containing the fragment was observed in at least two adjacent sections, the interaction was classified as trogocytosis (Uribe-Querol & Rosales 2021). There were many instances in which neurons simply indented the membrane of the microglial cell, and these were not counted.
Results: Ramified microglial cells #1, #50688, #50636, #50635 trogocytosed all major cell types of inner retinal including OFF midget ganglion cell, ON midget ganglion cell, OFF parasol ganglion cell, OFF midget bipolar cell, ON midget bipolar cell, OFF bipolar Cell (DB2), blue cone bipolar cell, ON diffuse bipolar cell (DB4), knotty type 2/A3 amacrine cell, AII amacrine cell, wide-field amacrine cell, narrow-field amacrine cell, knotty A1 amacrine cell, and Müller glial cells. In total, the five microglial cells trogocytosed 93 cells: 16 ganglion cells, 9 bipolar cells, 34 amacrine cells, 8 neuronal fragments and 26 Müller glial cells.
Conclusions: Here we report that microglia serve a homeostatic function in the adult macaque retina. We found that ramified microglia frequently ingested pieces of each of the major types of inner retinal neurons and Müller glial cells via trogocytosis. We only saw one instance in which the interaction took place at a synapse, a finding suggesting that the microglia are not engaged in synaptic remodeling. Instead, we propose that microglia contribute to immune surveillance by presenting antigens from normal inner retinal cells.