Simple and complex retinal dystrophies are associated with profoundly different disease networks



Christina Kiel, Claire Lastrucci, Philip J. Luthert, Luis Serrano et al.

Description of the technology

Retinopathies, or retinal dystrophies, are a group of monogenetic or complex diseases causing degeneration of the retina. Affected people generally experience a gradual loss of vision that may lead to blindness. Monogenetic disorders are caused by rare genetic variation and usually arise early in life. Other diseases, such as age-related macular degeneration (AMD), develop late in life and are considered to be of complex origin as they develop from a combination of genetic, ageing, environmental and lifestyle risk factors.

The technology uses network-based methods (theory of disease network) for comparison of the underlying disease networks of genes and pathological mechanisms of monogenic and complex retinopathies, using AMD as an example of the latter. The developers of this technology have showed that, surprisingly, networks of genes associated with the different forms of retinopathies in general do not overlap despite their overlapping retinal phenotypes. Further, AMD risk genes participate in multiple networks with interaction partners that are not connected. For those genes-partners the associated cellular and physiological functions with respect to vision loss cannot be directly predicted based on the integration with published interaction networks. Besides, mentioned partners and their networks link to different ubiquitous pathways affecting general tissue integrity and homeostasis. Thus, AMD most likely represents an endophenotype with differing underlying pathogenesis in different subjects. Localising these pathomechanisms and processes within and across different retinal anatomical compartments provides a novel representation of AMD that may be extended to complex retinopathies in general. This approach may generate improved treatment options that target multiple processes with the aim of restoring tissue homeostasis and maintaining vision.

Practical application

This technology shows the place of network-based approach in investigations and development of therapeutic methods of different types of retinal dystrophies. This approach is highly effective for simple retinopathies and helps to develop the treatment for these diseases.

However, for complex retinal dystrophies a gene-/network- and pathway-centric (interactome) approach does not guide the way to the physiologically distinct functions directly relevant to vision. To go beyond these limitations information derived from physiology and interactomics must be combined and its interrelation with tissue processes centre stage must be determined. In prospect integrating and connecting these processes within retinal cell and compartment states may facilitate the generation of multiscale agent-based models of AMD pathogenesis. In turn, these models may serve as the cornerstone for integrative risk prediction of age-related macular degeneration for patients.


  • EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona (Spain)
  • Universitat Pompeu Fabra (UPF), Barcelona (Spain)
  • Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, and NIHR Biomedical Research Centre, University College London, London (UK)
  • Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona (Spain)



  • Kiel, C. et al. «Simple and complex retinal dystrophies are associated with profoundly different disease networks." 7 Scientific Reports (2017): 41835.
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  • Rakoczy, E.P. et al. «Analysis of disease-linked rhodopsin mutations based on structure, function, and protein stability calculations." 405 J. Mol. Biol. (2011): 584–606.