Effect of microglia suppression on branch retinal vein occlusion in mice

Abstract

PurposeActivation of retinal microglia seems to have an influence on the outcome of retinal degenerative diseases. Recent studies show that systemic colony stimulating factor‐1 receptor (CSF‐1R) inhibition ablates microglia in the mouse central nervous system. However, the role of microglia inhibition in ischemic retinal disease remains unclear. The present study aims at investigating the effect of microglia depletion in vivo in experimental branch retinal vein occlusion (BRVO).MethodsCx3cr1gfp/+ mice, specifically expressing green fluorescent protein (gfp) on microglia/macrophages, were fed with the CSF‐1R inhibitor PLX5622 in mouse chow for two weeks before laser‐induced BRVO. Following BRVO, one group of animals was continuously treated with PLX5622 for three more weeks (PLX5622 group), while a second group was switched to normal diet (PLX5622 cessation group). Anatomical changes in the retina and gfp+ cell distribution were monitored weekly with optical coherence tomography and scanning laser ophthalmoscopy autofluorescence imaging (AF), respectively. Every week, 2–3 animals of each group were euthanized for histology. Retinal whole mounts stained for iba‐1 (microglia/macrophages) and brn3a (ganglion cells) were compared to in vivo AF images.ResultsAccumulation of gfp‐expressing cells in the area affected by BRVO was observed shortly after the laser in both groups. However, this accumulation was less pronounced in the PLX5622 treated group. Surprisingly, ganglion cell numbers were significantly decreased in the PLX5622 cessation group compared to the PLX5622 Group.ConclusionsThe data provided here showed that CSF‐1R inhibition has a protective effect on ganglion cells after experimental BRVO. Thus, such inhibitiors may be a promising tool for modulation of retinal microglia and could be proven a useful target for ischemic retinal diseases.