First Author: C.Brockmann GERMANY
Co Author(s): S. Dege N. Kociok O. Strauss A. Joussen
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To investigate the influence of C5a on retinal neovascularization in mice with oxygen-induced retinopathy (OIR).
Pre clinical experimental animal study.
Young wild type mice (C57BL/6) were exposed to an oxygen level of 75% from postnatal (P) day 7 to 12 for OIR induction. C5a was daily injected intraperitoneally from P12 to P16. Phosphate buffered saline (PBS) was used for control mice. A third group received a C5a inhibitor (NOX-D20). Avascular areas and neovascular tufts were investigated in retinal flatmounts at P14, P17 and P21 (n = 6-8 eyes per group and time point). In addition qPCR was performed to evaluate RNA expression of different complement factors. Furthermore cluster of differentiation (CD) 11b positive cells were quantified and compared between the injection groups, separately for avascular areas, neovascular tufts and physiologically vascularized areas.
After C5a injections the avascular area was significantly reduced by one third at P17 compared to PBS injected mice (p < 0.05). Likewise the tuft area was reduced by two thirds in the C5a group compared to the PBS group at P17 (p = 0.006). Within the avascular area the number of CD11b positive cells was reduced by one third after C5a injection versus PBS at P17 (p < 0.001). Similar distribution patterns between the C5a and PBS group were found for CD11b positive cells within the tuft areas at P17. No significant differences were found between the NOX and PBS group regarding avascular area, tuft and CD11b distribution at P17. RNA expression revealed increased levels of C3 and C1q, decreased values of Properdin after OIR induction with C5a injection.
Systemic C5a does influence the extent of avascular area and tufts in the murine OIR model. Moreover the distribution of rertinal CD11b positive cells differs after systemic C5a application, indicating a relevant interaction of C5a and CD11b positive cells in OIR. This study supports the importance of the complement system with regard to neovascular retinal diseases.