Abstract
Purpose :
Albinism is a group of disorders characterised by a lack of pigment and abnormal retinal development. Despite being a common cause for visual impairment world-wide, there are few treatments and patients typically suffer life-long visual disability. To develop a targeted and effective treatment for albinism-linked visual impairment, the role of the pigment synthesis pathway in normal ocular development needs to be interrogated. The aim of this study was to characterise the phenotypic differences in the retina of C57BL/6-c2J (CALB) mouse model of human oculocutaneous albinism (OCA) compared to normally pigmented C57BL/6 (B6) mice.
Methods :
Components of the dopaminergic signalling pathway in the developing retina of untreated CALB and B6 mice were studied by immunohistochemistry (IHC) at E11, 12, 16, 17 and W4, 5, 6, 8, 12, 16, with n=3 per group per time point. We looked at the distribution of ocular albinism 1 (OA1) and dopaminergic D2 receptors, DOPA decarboxylase (DD) and tyrosine hydroxylase (TH). Images were taken using a high-resolution dot-slide scanner and quantified using Image-J software. Intensity of the signal was analysed to determine semi-quantitative changes of expression of the molecules tested.
Results :
At E12-17 OA1 was expressed throughout the CALB retina. In contrast, OA1 was only expressed in the inner layers of the B6 retina. At 8 weeks OA1 was observed in the inner nuclear layer (INL) of the B6s and in the inner plexiform layer (IPL), INL, ONL and choroid of the CALBs. At 12 weeks, OA1 expression was evident in the INL and ONL of both B6s and CALBs and in the choroid of CALBs. By 16 weeks, OA1 is weakly present in the RPE only in B6s, whilst the CALBs have persistent OA1 expression in the ONL and choroid.
At 8-16 weeks D2 was expressed in the retinal pigment epithelium (RPE) and the outer nuclear layer (ONL) of CALBs and B6s, although notably at reduced levels in the CALBs. DD was strongly expressed in the RPE of CALBs and B6s. TH was expressed in the RPE in B6s and in the choroid of the CALBs.
Conclusions :
There are differences in albinism in the expression of key components of the dopaminergic signalling pathway throughout retinal development. These abnormalities appear to be focused on the OA1 and dopaminergic D2 receptors, making them potential targets for new treatments against albinism.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.