HDAC inhibition in the cpfl1 mouse protects degenerating cone photoreceptors in vivo.

Abstract

Cone photoreceptor cell death as it occurs in certain hereditary retinal diseases is devastating, with the affected patients suffering from a loss of accurate and colour vision. Regrettably, these hereditary cone diseases are still untreatable to date. Thus, the identification of substances able to block or restrain cone cell death is of primary importance. 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 cpfl1 cones in vitro, in retinal explant cultures. More importantly, in vivo, a single intravitreal TSA injection significantly increased cone survival for up to 16 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 retinal diseases associated with impaired cone migration.

• Authors: Dragana Trifunović, Blanca Arango-Gonzalez, Antonella Comitato, Melanie Barth, Eva M Del Amo, Manoj Kulkarni, Ayse Sahaboglu, Stefanie M Hauck, Arto Urtti, Yvan Arsenijevic, Marius Ueffing, Valeria Marigo, François Paquet-Durand
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 25 Issue 20 Pg. 4462-4472 (10 15 2016) ISSN: 1460-2083 [Electronic] England
• PMID: 28172811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Neuroprotective Agents
• trichostatin A

Topics

• Animals
• Disease Models, Animal
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Hydroxamic Acids (pharmacology, therapeutic use)
• Mice
• Neuroprotective Agents (pharmacology, therapeutic use)
• Retinal Cone Photoreceptor Cells (drug effects, pathology)
• Retinal Degeneration (drug therapy)