UCSF

Retinopathy of prematurity (ROP) is one of the leading causes of childhood visual impairment and blindness. However, there are still very few effective pharmacological interventions for ROP. Histone deacetylase 6 (HDAC6)-mediated disassembly of photoreceptor cilia has recently been implicated as an early event in the pathogenesis of ROP. Herein it is shown that enhanced expression of HDAC6 by intravitreal injection of adenoviruses encoding HDAC6 induces the typical pathological changes associated with ROP in mice, including disruption of the membranous disks of photoreceptor outer segments and a decrease in electroretinographic amplitudes. Hdac6 transgenic mice exhibit similar ROP-related defects in retinal structures and functions and disassembly of photoreceptor cilia, whereas Hdac6 knockout mice are resistant to oxygen change-induced retinal defects. It is further shown that blocking HDAC6-mediated cilium disassembly by intravitreal injection of small-molecule compounds protect mice from ROP-associated retinal defects. The findings indicate that pharmacological targeting of the HDAC6-cilium axis may represent a promising strategy for the prevention of ROP.