Article Text

PDF
Original article
C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration
  1. Imran A Bhutto,
  2. Takayuki Baba,
  3. Carol Merges,
  4. Vikash Juriasinghani,
  5. D Scott McLeod,
  6. Gerard A Lutty
  1. Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA
  1. 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

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

Statistics from Altmetric.com

Footnotes

  • 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.

  • Competing interests None.

  • 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.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • At a glance
    Harminder S Dua Arun D Singh