The Chx10-Traf3 Knockout Mouse as a Viable Model to Study Neuronal Immune Regulation.

Uncontrolled inflammation is associated with neurodegenerative conditions in central nervous system tissues, including the retina and brain. We previously found that the neural retina (NR) plays an important role in retinal immunity. Tumor necrosis factor Receptor-Associated Factor 3 (TRAF3) is a known immune regulator expressed in the retina; however, whether TRAF3 regulates retinal immunity is unknown. We have generated the first conditional NR- knockout mouse model (-Cre/) to enable studies of neuronal TRAF3 function. Here, we evaluated NR- depletion effects on whole retinal TRAF3 protein expression, visual acuity, and retinal structure and function. Additionally, to determine if NR- plays a role in retinal immune regulation, we used flow cytometry to assess immune cell infiltration following acute local lipopolysaccharide (LPS) administration. Our results show that TRAF3 protein is highly expressed in the NR and establish that NR- depletion does not affect basal retinal structure or function. Importantly, NR- promoted LPS-stimulated retinal immune infiltration. Thus, our findings propose NR- as a positive regulator of retinal immunity. Further, the NR- mouse provides a tool for investigations of neuronal TRAF3 as a novel potential target for therapeutic interventions aimed at suppressing retinal inflammatory disease and may also inform treatment approaches for inflammatory neurodegenerative brain conditions.