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Minzhong Yu, Weilin Zou, Neal S. Peachey, Thomas McIntyre, Jinbo Liu; A Role For Complement Activation In Preventing Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1232.
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The observations that single nucleotide polymorphisms of complement alternative pathway components are associated with the risk of AMD development indicate that complement plays an important role in AMD pathology. How these variants lead to photoreceptor degeneration is not known. To better understand the relationship between complement activation and the retina, we examined mice lacking the receptors for complement activation fragments C3a (C3aR-/-), C5a (C5aR-/-) or both (C3aR-/-/C5aR-/-).
Complement mutant mice (C3aR-/-; C5aR-/-; C3aR-/-/C5aR-/-) were studied along with WT littermates from ages of 6 weeks up to 14 months. After overnight dark adaptation, strobe flash ERGs were used to examine outer retinal function and a dc-ERG technique was used to measures ERG components generated by the retinal pigment epithelium (RPE). Retinas were examined by immunohistochemistry and microscope.
C3aR was localized to the RPE and all cell layers of the neural retina; C5aR expression was restricted to the RPE and ganglion cell layer. We observed a progressive decline of ERG a- and b-wave amplitudes in C3aR-/- and C3aR-/-/C5aR-/-mice, which was correlated with cellular losses in the ONL and INL. These changes were not observed in C5aR-/- animals. Amplitude reductions were, however, noted in dc-ERGs recorded from C5aR-/- mice.
Genetic deletion of receptors for the complement activation fragments C3a and C5a leads to cell-specific defects that match the cellular localization of these receptors in the WT retina. These indicate that receptor signaling through these pathways contribute to retinal cell survival.
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