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Huiyang Zeng, Qing-jun Lu, Qian Liu, Ke-gao Liu, Ning-li Wang; The Role Of RANTES And Chemokine Receptors In The Retinal Degeneration In Rd Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1008.
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Chemokine and chemokine receptors are reported to be involved in neuronal cell death and CNS neurodegenerative diseases. Our previous study suggested activation of microglia might play a major role in the retinal degeneration in rd mice and CC chemokines were involved in the activation of microglial cells. The aim of current study was to further investigate the expression of RANTES and its receptors in the rd retina and explore their role in the photoreceptor degeneration.
The expression of RANTES,CCR1,CCR3 and CCR5 in the mRNA or/and protein level in the whole retina of control and rd mice at different age group were determined by RT-PCR or/and immunohistochemical analysis . Expression of gp91phox and iNOS in the rd retina at each age group was studied by western blot analysis and immunostaining. Cellular location of RANTES, CCR1, CCR5, iNOS and gp91phox in the retina was determined by double labeling.
Besides significant up-regulation of mRNA in the rd retina,RANTES immunoreactivity was seen on the CD11b-postive retinal microglial cells . CCR1 and CCR5 mRNA was moderately elevated in the rd retina peaking at postnatal day (P) 12 and P14. Immunoreactivity of CCR1 on the photoreceptors and CCR5 on the activated retinal microglial cells were found to be increased in the rd mice. Partial CCR1 expression on some of the apoptotic photoreceptor cells was noted in the degenerated retina.CCR3 was expressed on the neurons in the inner retina of rd and control mice equally. Elevated expression of iNOS and gp91phox were found in the rd retinas at P8 and reached peak at P12 and P14. In the rd retina, immunoreactivity of iNOS was observed on the photoreceptor cells while gp91phox was seen on the microglial cells. Part of gp91phox and iNOS were co-localized with CCR5 and CCR1 respectively.
Elevated expression of RANTES and its receptors, as well as activation of oxidative markers on the same cell type, precedes the ocurrence(P10) and peak (P16) of photoreceptor apoptosis, suggesting that RANTES 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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