Purchase this article with an account.
Damien Pike, Helene Paradis, Maria Whalen, Bimal Tennakoon, Robert Gendron; Tubedown Regulation of Retinal Blood Vessel Permeability During Aging and Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5237.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Tubedown (Tbdn) is a regulatory subunit of the acetyltransferase Ard1 that is specifically expressed in retinal blood vessels and necessary for retinal health through control of blood vessel permeability. Tbdn is suppressed during aging and even more so in wet age-related macular degeneration. Previous work indicates that loss of Tbdn causes pathological changes driving retinopathy. Maintenance of Tbdn expression during aging and age-related retinopathy as a potential therapeutic approach for preventing pathology has not been explored and the impact of Ard1 on retinal blood vessel permeability is unknown.
The impact of the maintenance of Tbdn expression in the vasculature on retinal pathology during aging in transgenic mice was studied using histomorphometry, optical coherence tomography (OCT), quantitative immunohistochemistry and Western blotting. The role of Ard1 on retinal endothelial cell permeability was studied using both knockdown and overexpression.
Overexpression of Ard1 in retinal endothelial cells led to an increased permeability to Albumin. Ard1 knockdown led to a modest reduction in Albumin permeability. Retinal pathology and thickness was reduced in aged mice which overexpressed Tbdn in the vasculature. Moreover, Tbdn overexpression in aged mice decreased the hyperpermeability of retinal blood vessels to Albumin.
Our results have shown that Tbdn dampens permeability while Ard1 promotes it. As a regulatory subunit of the acetyltransferase complex Ard1/Tbdn, Tbdn possibly reduces the efficacy of the complex to acetylate a target which would promote permeability, or inversely, Tbdn could facilitate the acetylation of a substrate which would dampen permeability. Our results also imply that the maintenance of Tbdn expression in retinal blood vessels could serve as a useful strategy to prevent retinal pathology during aging.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only