Is Macular Degeneration Caused by C-Reactive Protein?

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In a 2017 study, researchers explored the association between single nucleotide polymorphisms of the C-reactive protein gene and age-related macular degeneration. The findings suggest that C-reactive protein does not cause macular degeneration.


Associations have been drawn between high levels of the inflammatory biomarker C-reactive protein (CRP) and age-related macular degeneration (AMD) – deterioration of the eye’s macula, the part of the retina which determines how sharply we see an image. Whether high CRP levels contribute to the development of age-related macular degeneration is currently unknown – it may be a cause or it may be a by-product of a common cause.

Previous studies have examined the relationship between forms of the CRP gene and age-related macular degeneration. Forms of the CRP gene are termed single nucleotide polymorphism (SNP) because they differ by one DNA nucleotide. However, the previous studies may have been too small to generate meaningful results.

In order to understand the factors influencing age-related macular degeneration, more research is needed on the association between CRP SNPs and age-related macular generation. These will help improve methods of prevention, treatment, and management.

Examining the Association between CRP genes and Macular Degeneration

In a recent analysis published in JAMA Ophthalmology, researchers examined the association between CRP SNPs and AMD risk. Data was collected from 3 studies on CRP and AMD: the 2000-2002 European Eye ) study, the 2001-2007 Cambridge AMD study, and the 2001-2004 Moorfields Eye Hospital ) AMD study.

In each study, researcher’s photographed patients’ retinas and unaffected controls and drew blood samples. They graded age-related macular degeneration on a scale from 0 to 4:

  • Grade of 0: Represented no clear evidence of AMD.
  • Grades 1 and 2: Represented early AMD, characterized by hard or soft, medium-to-large fatty deposits beneath the retina or changes in pigmentation.
  • Grade 3: Represented intermediate AMD, characterized by large fatty deposits and changes in pigmentation.
  • Grade 4: Represented late AMD, characterized by the growth of abnormal, leaky blood vessels or detachment of the retina from the back of the eye (neovascular AMD), by death of the light-sensitive cells of the macula and its supporting tissue (geographic atrophy), or both (mixed).

The EUREYE and Cambridge studies examined levels of CRP in the blood. Those with levels above 10 mg/L were excluded; as such levels might suggest infection. Patients and controls were screened for the CRP gene SNPs rs1205, rs1130864, rs1800947, and rs3093077.

Findings

Among the three studies, there were 1,727 cases of late AMD – 1151 neovascular AMD cases, 384 geographic atrophy cases, and 192 mixed cases. A significant association was found between geographic atrophy and CRP level. CRP levels were significantly lower in controls with 1 or 2 copies of rs1205 compared to controls without the SNP.  Conversely, controls with 1 or 2 copies of rs1130864 had significantly higher CRP levels than those without the SNP. No associations were found between CRP levels or CRP SNPs and early or late AMD.

C-Reactive Protein Not a Cause of Macular Degeneration

The study’s findings suggest that C-reactive protein does not cause macular degeneration. Though CRP genotype affected CRP levels and higher CRP levels were linked to geographic atrophy, neither CRP genotype nor CRP levels were significantly associated with age-related macular degeneration.

CRP levels in the studies were measured at the time of examination, and as such, future research may benefit from examining CRP levels over multiple time points to better determine a causal relationship between the factors. As CRP is linked to inflammation in general, levels in the bloodstream may have been influenced by inflammatory conditions and factors such as smoking or cardiovascular disease.

This important study demonstrates that while there may be an association, C-reactive protein (CRP) does not cause age-related macular degeneration.

Written by Raishard Haynes, MBS

Cipriani, V. et al. (2017). Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2017.2191

 

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