Abstract
BackgroundThe recruitment of macrophages accompanies almost every pathogenic state of the retina, and their excessive activation in the subretinal space is thought to contribute to the progression of diseases including age-related macular degeneration. Previously, we have shown that macrophages aggregate in the outer retina following damage elicited by photo-oxidative stress, and that inhibition of their recruitment reduces photoreceptor death. Here, we look for functional insight into macrophage activity in this model through the spatiotemporal interplay of macrophage polarisation over the course of degeneration.MethodsRats were exposed to 1000 lux light damage (LD) for 24hrs, with some left to recover for 3 and 7 days post-exposure. Expression and localisation of M1- and M2- macrophage markers was investigated in light-damaged retinas using qPCR, ELISA, flow cytometry, and immunohistochemistry.ResultsExpression of M1- (Ccl3, Il-6, Il-12, Il-1β, TNFα) and M2- (CD206, Arg1, Igf1, Lyve1, Clec7a) related markers followed discrete profiles following light damage; up-regulation of M1 genes peaked at the early phase of cell death, while M2 genes generally exhibited more prolonged increases during the chronic phase. Moreover, Il-1β and CD206 labelled accumulations of microglia/macrophages which differed in their morphological, temporal, and spatial characteristics following light damage.ConclusionsThe data illustrate a dynamic shift in macrophage polarisation following light damage through a broad swathe of M1 and M2 markers. Pro-inflammatory M1 activation appears to dominate the early phase of degeneration while M2 responses appear to more heavily mark the chronic post-exposure period. While M1/M2 polarisation represents two extremes amongst a spectrum of macrophage activity, knowledge of their predominance offers insight into functional consequences of macrophage activity over the course of damage, which may inform the spatiotemporal employment of therapeutics in retinal disease.
Highlights
Recruitment and activation of macrophages is prominent feature of virtually all pathogenic states of the retina
The data illustrate a dynamic shift in macrophage polarisation following light damage through a broad swathe of M1 and M2 markers
Macrophage Polarisation in Retinal Degeneration dominate the early phase of degeneration while M2 responses appear to more heavily mark the chronic post-exposure period
Summary
Recruitment and activation of macrophages is prominent feature of virtually all pathogenic states of the retina. Microglia/macrophage infiltration (hereby referred to collectively as ‘macrophages’ for brevity) is well-characterised in a range of human dystrophies such as age-related macular degeneration (AMD) [2,3,4,5,6], retinitis pigmentosa [3], retinal detachment [7], glaucoma [8,9,10], and diabetic retinopathy [8,11]. Despite their beneficial homeostatic properties, excessive macrophage activation may result in damage to the neural environment. We look for functional insight into macrophage activity in this model through the spatiotemporal interplay of macrophage polarisation over the course of degeneration
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