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Huiyang Zeng, Qian Liu, Qing-jun Lu, Ke-gao Liu, Ning-li Wang; The Role Of CC Chemokines And Their Receptors In The Retinal Degeneration In Rd Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1656.
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Our previous studies showed that CC chemokines and CCR1,one of the CC chemokine receptors, were involved in the retinal degeneration in the rd mice. The aim of current study was to further investigate the expression of CC chemokines and their other receptors in the rd retina and explore their role in the photoreceptor degeneration.
Expression levels of CC chemokine receptors transcripts including CCR2,CCR3 and CCR5 in the whole retina in the control and rd mice at postnatal days (P) 8,10,12,14,16 and 18 were determined by RT-PCR assay. Location of CC chemokines including MCP-1,MCP-3, MIP-1a,MIP-1βand RANTES and their above receptors were studied by immunohistochemical analysis. Expression of gp91phox and iNOS in the rd retina at each age group was studied by real-time PCR analysis and immunostaining. Cellular location of CCR5, iNOS and gp91phox in the retina was determined by double labeling.
CCR3 and CCR5 mRNA was significantly up-regulated in the rd retina from P12 to P16 while CCR2 mRNA was down-regulated when compared with the controls. RANTES immunoreactivity was seen on the CD11b-postive retinal microglial cells while other CC chemokines were expressed in the neurons of inner retina. Immunoreactivity of CCR5 on the activated retinal microglial cells were found to be increased in the rd mice. CCR2 and CCR3 were expressed on the neurons in the inner retina of rd and control mice. Expression of gp91phox and iNOS transcripts began to increase in the rd retinas at P10d and P8d respectively, reached peak at P12d and maintained a high level until P16d. In the rd retina, immunoreactivity of gp91phox was observed on the microglial cells while iNOS was observed on the photoreceptor cells. Part of gp91phox and iNOS were co-localized with CCR5 and CCR1 (expressed on the photoreceptor as shown in our published study) respectively.
Activation of CC chemokines receptors, especially CCR5 and CCR1, as well as activation of oxidative markers on the same cell type, were correlated with or precedes the occurrence (P10) and peak (P16) of photoreceptor apoptosis, suggesting that CC chemokines may play a role in the retinal degeneration in rd mice either indirectly through activation of microglial cells killing mechanism( activation of CCR5) or directly through activation of chemokine receptors (CCR1) on photoreceptor cells.
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