Abstract
Purpose :
Low levels of tubedown (TBDN, NAA15), a mammalian homologue of the yeast acetyltransferase subunit NAT1, are implicated in proliferative retinopathies such as wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR). TBDN is specifically expressed in retinal and choroidal blood vessels and is necessary for retinal health through control of blood vessel permeability. The effects of TBDN deficiency have been characterized via retinal histopathology in a mouse model; however, clinical correlation with spectral domain optical coherence tomography (SD-OCT) on live animals remains unclear. Our hypothesis is that TBDN deficiency manifests as increased retinal thickness on SD-OCT using an endothelial specific TBDN knockdown mouse model.
Methods :
The experimental cohort (N=10) comprised middle age transgenic mice with conditional TBDN knockdown in the vasculature induced with doxycycline. The control cohort (N=10) comprised middle age transgenic non-induced and control-induced mice. Levels of TBDN expression in the retinal and choroidal tissues were determined by Western blot and immunostaining. The SD-OCT platform used was the Bioptigen Envisu R2210 and en-face scans of both eyes in regular and Doppler modes were collected. Central retinal thickness was measured from the retinal nerve fibre layer to the retinal pigment epithelium. Two-tailed t-test was used for statistical analysis.
Results :
Levels of TBDN in the retinal and choroidal tissues were reduced by approximately 50% in the TBDN knockdown mice compared to controls. Initial analysis shows central retinal thickness measured 229.35±0.42μm in the TBDN knockdown mice (N=4) and 208.24±0.45μm in the control mice (N=4). These findings reveal that TBDN deficiency manifests as significantly increased central retinal thickness (p<0.0001) on SD-OCT, which is consistent with previous histological findings. Further analysis of retinopathy in the SD-OCT scans will be presented.
Conclusions :
These findings support our hypothesis that TBDN deficiency imparts morphologic changes in the retina by confirming the correlation between histopathology and SD-OCT on the TBDN knockdown mouse model. Our study reinforces the deleterious role of TBDN deficiency in proliferative retinopathies, such as wet AMD and DR.
This is a 2020 ARVO Annual Meeting abstract.