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bioRxiv · 10.1101/049742

HDAC inhibition protects degenerating cone photoreceptors in vivo

Dragana Trifunovic·Blanca Arango-Gonzalez·Antonella Comitato·Melanie Barth·Ayse Sahaboglu·Eva del Amo·Manoj Kulkarni·Stefanie Hauck·Marius Ueffing·Arto Urtti·Yvan Arsenijevic·Francois Paquet-Durand
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Abstract

Retinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

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Dragana Trifunovic, Blanca Arango-Gonzalez, Antonella Comitato, Melanie Barth, Ayse Sahaboglu, Eva del Amo, Manoj Kulkarni, Stefanie Hauck, Marius Ueffing, Arto Urtti, Yvan Arsenijevic, Francois Paquet-Durand. 2016-04-22. HDAC inhibition protects degenerating cone photoreceptors in vivo. https://doi.org/10.1101/049742

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