C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration
- Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA
- Correspondence to Gerard A Lutty, Wilmer Ophthalmological Institute, M041 Smith Building, Johns Hopkins Hospital, 400 North Broadway, Baltimore, MD 21287-9115, USA; galutty{at}jhmi.edu
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Contributors IAB, TB and CM carried out experiments. IAB, TB, VJ and GAL graded and analysed data. DSM captured the immunohistochemistry images and prepared the graphs. IAB, DSM and GAL conceived experiments and all authors were involved in writing the paper and had final approval of the submitted and published versions.
- Accepted 15 April 2011
- Published Online First 1 June 2011
Abstract
Background There is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the gene encoding complement factor H (CFH) and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have consistently been shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalisation of CRP and CFH in aged control human donor eyes (n=10; mean age 79 years) and eyes with AMD (n=18; mean age 83 years).
Methods Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0–8).
Results In aged control eyes, the retinal pigment epithelium/Bruch's membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographical atrophy (p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH.
Conclusion These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD.
- Age-related macular degeneration
- C-reactive protein
- complement factor H
- retina/choroid interface
- immunohistochemistry
- choroid
- retina
- macula
- inflammation
- neovascularisation
Footnotes
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Funding This work was supported by NIH grants: EY-01765 (Wilmer) and R01-EY016151 (GAL), unrestricted funds from Research to Prevent Blindness (Wilmer), the Foundation Fighting Blindness (GAL), American Health Assistance Foundation (GL), and the Altsheler Durell Foundation. GAL received an RPB Senior Scientific Investigator Award.
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Competing interests None.
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Ethics approval This study was conducted with the approval for the use of post mortem tissue from the Johns Hopkins JCCI. The protocol of the study adhered to the tenets of the Declaration of Helsinki regarding research involving human tissue.
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Provenance and peer review Not commissioned; externally peer reviewed.
