Purchase this article with an account.
M. Hu, B. Liu, S. Chakrabarty, M. Casady, R. B. Nussenblatt; Complement Fragment C5a Activates Retinal Pigment Epithelial Cells and Contributes to the Pathogenesis of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3505.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate complement fragment C5a’s effects on retinal pigment epithelial (RPE) cells and how these effects may play a role in the pathogenesis of age-related macular degeneration (AMD).
Human adult RPE and ARPE-19 cells were used in this study. An MTT assay was used to detect cell growth and viability. A real-time polymerase chain reaction was used to detect cytokine mRNA expression. C5a was added to RPE-PBMC co-cultures and a tritiated thymidine incorporation assay was used to detect cell proliferation.
C5a slightly inhibited RPE cell growth. C5a also down-regulated chemokine receptors CX3CR1 and CXCR5 expression on RPE cells by 24 hours. In addition, C5a abrogated RPE cells’ suppressive effects on T cells and this abrogation was reversible with a C5aR antagonist. These results are seen in both primary human RPE cells and ARPE-19 cells.
Our study demonstrates that C5a decreased RPE cell viability, a finding that may explain the geographic atrophy seen in "dry" AMD. C5a down-regulated certain chemokine receptors, which may lead to dysfunction of leukocyte trafficking and decrease the elimination of macular debris. We provide evidence that C5a abrogated RPE cells’ suppressive effects on T cells, which could increase inflammation in the eye. Together, these findings suggest C5a might play a role in the pathogenesis of AMD.
This PDF is available to Subscribers Only