Genetic Polymorphisms and the Phenotypic Characterization of Individuals with Early Age-Related Macular Degeneration

Ophthalmologica. 2017;238(1-2):6-16. doi: 10.1159/000468949. Epub 2017 May 31.

Abstract

Purpose: While the importance of risk polymorphisms for the pathogenesis of age-related macular degeneration (AMD) is well established, their impact on morphological and functional phenotypes is largely unclear. We aimed to characterize individual phenotypes in patients who were either homozygous for a risk allele in the CFH gene, ARMS2 gene, or both as compared to non-carriers.

Methods: Patients with early AMD (n = 85) were assessed during a follow-up examination of a prospective study (MARS) with multimodal diagnostics including SD-OCT and microperimetry.

Results: Compared to non-carriers, OCT scans revealed lower retinal thickness in patients homozygous for CFH or ARMS2, which was caused by a significantly reduced photoreceptor layer. The number and ultrastructure of drusen were also significantly different.

Conclusions: These findings indicate that patients with risk alleles demonstrate distinct phenotypic differences of morphology and function as compared to non-carriers. In particular in the CFH group, a loss of photoreceptors occurred concomitantly with reduced retinal sensitivity. Further studies might help to better understand the pathophysiology.

Keywords: Drusen; Early age-related macular degeneration; Genetic polymorphisms; Microperimetry; Phenotypic differences; Phenotyping; Risk factors; SD-OCT; Single nucleotide polymorphisms.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Complement Factor H / genetics
  • Complement Factor H / metabolism
  • Cross-Sectional Studies
  • DNA / genetics*
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Macula Lutea / pathology*
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Prospective Studies
  • Proteins / genetics*
  • Proteins / metabolism
  • Time Factors
  • Tomography, Optical Coherence

Substances

  • ARMS2 protein, human
  • CFH protein, human
  • Proteins
  • Complement Factor H
  • DNA