Common Mechanisms for Separate Maculopathies?

  • Elod KortvelyEmail author
  • Marius Ueffing
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


Maculopathies include Mendelian monogenic (familial) as well as complex (sporadic) diseases that primarily afflict the central retina. Although prevalence, onset, inheritance, and clinical manifestation may differ substantially among macular diseases, emerging evidence suggests overlapping pathogenic pathways. We propose here a hypothesis connecting familial and sporadic maculopathies on the basis of overlapping protein networks, which also systematically integrate nongenetic (environmental) risk factors. Based on the function and network connectivity of proteins and metabolites implicated in these maculopathies, three major areas can be outlined: (1) lipid metabolism, (2) the extracellular matrix (ECM), and (3) the complement system. On the physiological level, extracellular deposition of waste products with high lipid content is a characteristic of most maculopathies, suggesting that perturbed lipid metabolism and subsequent deposition of its extracellular components in ECM (e.g., by forming hydrophobic barriers between intra- and extracellular compartments) plays a significant role. Extracellular microanatomical barriers composed of lipoproteinaceous structures (like the Bruch’s membrane) receive protection against degradation through complement factor H (CFH), a critical negative regulator of alternative complement pathway activation. As such, all three areas, primarily defined by genetic association or linkage analysis, may compose a disease network with distinct but interconnected molecular areas. The concept of overlapping disease phenotypes based on overlapping networks and etiologies bears potential to define directions of future research and help to pinpoint candidate genes for maculopathies of unknown origin, where the disease causing mutation has been narrowed down to a chromosomal region harboring a limited number of genes.


Maculopathy Maculopathies AMD Familial Sporatic Lipid metabolism Extracellular matrix ECM Complement CFH Risk factors 


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Experimental OphthalmologyUniversity of TuebingenTuebingenGermany

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