Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration

Eleonora Vighi, Dragana Trifunovic, Patricia Veiga-Crespo, Andreas Rentsch, Dorit Hoffmann, Ayse Sahaboglu, Torsten Strasser, Manoj Kulkarni, Evelina Bertolotti, Angelique Van Den Heuvel, Tobias Peters, Arie Reijerkerk, Thomas Euler, Marius Ueffing, Frank Schwede, Hans Gottfried Genieser, Pieter Gaillard, Valeria Marigo, Per Ekström, François Paquet-Durand

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of “druggable” targets, and the access-limiting blood–retinal barrier (BRB) present major hurdles toward effective therapy development. Here, we address these challenges (i) by targeting cGMP (cyclic guanosine- 3′,5′-monophosphate) signaling, a disease driver common to different types of RD, and (ii) by combining inhibitory cGMP analogs with a nanosized liposomal drug delivery system designed to facilitate transport across the BRB. Based on a screen of several cGMP analogs we identified an inhibitory cGMP analog that interferes with activation of photoreceptor cell death pathways. Moreover, we found liposomal encapsulation of the analog to achieve efficient drug targeting to the neuroretina. This pharmacological treatment markedly preserved in vivo retinal function and counteracted photoreceptor degeneration in three different in vivo RD models. Taken together, we show that a defined class of compounds for RD treatment in combination with an innovative drug delivery method may enable a single type of treatment to address genetically divergent RD-type diseases.

Sidor (från-till)E2997-E3006
TidskriftProceedings of the National Academy of Sciences of the United States of America
StatusPublished - 2018 mars 27

Ämnesklassifikation (UKÄ)

  • Oftalmologi


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