Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology in Zebrafish and Mouse Models of Retinal Blindness.

Blindness arising from retinal or macular degeneration results in significant social, health and economic burden. While approved treatments exist for neovascular ('wet') age-related macular degeneration, new therapeutic targets/interventions are needed for the more prevalent atrophic ('dry') form of age-related macular degeneration. Similarly, in inherited retinal diseases, most patients have no access to an effective treatment. Although macular and retinal degenerations are genetically and clinically distinct, common pathological hallmarks can include photoreceptor degeneration, retinal pigment epithelium atrophy, oxidative stress, hypoxia and defective autophagy. Here, we evaluated the potential of selective histone deacetylase 6 inhibitors to preserve retinal morphology or restore vision in zebrafish atp6v0e1 -/- and mouse rd10 models. Histone deacetylase 6 inhibitor, tubastatin A-treated atp6v0e1 -/- zebrafish show marked improvement in photoreceptor outer segment area (44.7%, p = 0.027) and significant improvement in vision (8-fold, p ≤ 0.0001). Tubastatin A-treated rd10/rd10 retinal explants show a significantly (p = 0.016) increased number of outer-segment labeled cone photoreceptors. In vitro, ATP6V0E1 regulated HIF-1α activity, but significant regulation of HIF-1α by histone deacetylase 6 inhibition in the retina was not detected. Proteomic profiling identified ubiquitin-proteasome, phototransduction, metabolism and phagosome as pathways, whose altered expression correlated with histone deacetylase 6 inhibitor mediated restoration of vision

Systemic Treatment with Cigarette Smoke Extract Affects Zebrafish Visual Behaviour, Intraocular Vasculature Morphology and Outer Segment Phagocytosis

<p>Underlying dataset and analysis tests of the results described in the article "Systemic Treatment with Cigarette Smoke Extract Affects Zebrafish Visual Behaviour, Intraocular Vasculature Morphology and Outer Segment Phagocytosis".</p&gt

Priorities for rheumatic and musculoskeletal disease research in Ireland

Background: Research priority setting is a useful approach to decide which unanswered questions are most worth trying to solve through research. The aim is to reduce bias in the research agenda. Traditionally, research was decided by funders, policymakers, and academics with limited infuence from other stakeholders like people living with health conditions, caregivers, or the community. This can lead to research gaps that fail to address these important stake-holder needs. The objective of this study is to identify the top research priorities for Rheumatic and Musculoskeletal Disease (RMD) research in Ireland. Methods: The process framework included a design workshop, two online surveys and a review of the literature. Participants: 545 people completed the frst survey to identify RMD research topics relevant to Ireland, of which 72% identifed as a person living with RMD. 460 people completed the second survey to prioritise these research topics. Results: The frst survey had 2185 research topics submitted. These were analysed and grouped into 38 topic areas which were ranked in the second survey. The top three research priorities for RMD research in Ireland focused on preventing RMD progression, RMD diagnosis and its impact, and pain management. Conclusions: The prioritised research topics indicate important areas of RMD research for Ireland. Research funded in response to these co-created research priorities will have increased relevance and impact.</p