Purchase this article with an account.
D'Anne Duncan, Sean Lee, Rebecca Sappington; Expression of CCL5 Signaling Machinery in Healthy and Glaucomatous Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):435.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal inflammation is central to glaucomatous pathogenesis. The inflammatory mechanisms that influence retinal ganglion cell (RGC) function and survival provide insight into glaucomatous pathology and therapeutic strategies. In this study, we sought to examine the potential relevance of CCL5 signaling to RGCs in healthy and glaucomatous retina.
We performed immunohistochemistry to assess layer- and cell-specific expression of CCL5, CCR1, CCR3 and CCR5. Label intensity was quantified in retina layers using quantitative digital microscopy and image analysis software. Young (4 month) and aged (8 month) C57 mice were exposed to unilateral ocular hypertension for 4 weeks and RGC-specific expression of CCL5 and its receptors were assessed in whole mount retinas.
CCL5 and its receptors are constitutively expressed in multiple layers of the retina, with highest significant expression of CCL5 and CCR5 in ganglion cell (GCL) and nerve fiber layers (NFLs; p<0.002). In healthy retinal tissue, CCL5 and all 3 receptors co-localize with RGC somas and axons, while retinal glia (Müller glia, microglia and astrocytes) show restricted expression. In response to microbead-induced elevated IOP in vivo, young and aged RGCs exhibit significantly increased expression of CCL5 (p=0.042), but show decreased expression of CCR3 (p>0.01) and CCR5 (p=0.142), compared to saline-treated RGCs. Qualitatively, CCR1 showed increased expression, although this result was not significant.
These data support a functional role for constitutive and inducible CCL5 signaling in RGCs and provide evidence that CCL5 is relevant to RGC maintenance and glaucomatous pathology. Furthermore, expression of CCL5 machinery by RGCs and retinal glia, suggest potential autocrine and paracrine mechanisms of this chemokine in the retina.
This PDF is available to Subscribers Only