Dynamic interplay of innate and adaptive immunity during sterile retinal inflammation: Insights from the transcriptome

Background:The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immunity amongst the broad leukocyte infiltrate, and the gene networks which construct these responses, are largely unknown.Methods Using photo-oxidative damage in rodents as a model of subretinal inflammation, we employed RNA-sequencing to map the global gene signature of retinal leukocytes.Results: Functional network analysis of the retinal leukocyte population revealed a previously uncharted interplay of adaptive immunity during subretinal inflammation, illustrating prolonged enrichment of myeloid and lymphocyte migration, antigen presentation, and the alternative arm of the complement cascade involving Factor B. We demonstrate Factor B-deficient mice are protected against macrophage infiltration and subretinal inflammation.Conclusion: Suppressing the drivers of retinal leukocyte proliferation, or their capacity to elicit complement responses, may help perverse retinal structure and function during sterile inflammation in diseases such as AMD.Retinal mRNA profiles of adult wildtype rats (~p60) compared to 24 photo-oxidative damaged animals over a protracted post exposure timecourse (0, 3, 7 days) were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.