IL1A enhances TNF-induced retinal ganglion cell death.

Introduction: A growing body of literature suggests a role for neuroinflammation in retinal ganglion cell (RGC) death in glaucoma. For instance, deficiency of three proinflammatory cytokines, complement component 1, subcomponent q ( Methods: Eyes of 2-4 month-old C57BL/6J mice or mice deficient in either Results: Intravitreal injection of IL1A did not result in RGC death at either 14 days or 12 weeks. Consistent with previous studies, TNF injection did not cause significant RGC loss at 14 days but did after 12 weeks. Together, IL1A+TNF resulted in a relatively rapid RGC death, driving significant loss 2 weeks after injection. We identified molecular changes which occur in response to IL1A and to combined IL1A+TNF treatment with limited changes identified in TNF alone treated eyes. Using mice deficient in Discussion: We identified a novel role of IL1A, we found that IL1A acted as a sensitizer to TNF-induced death. Co-injection of IL1A and TNF resulted in rapid RGC death, with significant RGC loss 14 days after injection. TNF+IL1A-induced RGC death did not depend on JUN activation and was rather SARM1 dependent. Also, RNA-seq analyses indicated that while