Purchase this article with an account.
Shadi Safuri, Liat Bilgoray Brenner, Anat Loewenstein, Ido Perlman; Retinal Pigment Epithelium (RPE) cells facing cone photoreceptors display distinct transciptome with implications for the pathogenesis of Age-related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 201657(12):.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
RPE Cells interact with photoreceptors in a variety of ways acting together as a functional unit. As the retinas of most animal models used in retinal research are dominated by rods, little is known about RPE cells facing cones - the dominant type of photoreceptors at the human macula. This study tested whether the transciptome of RPE cells facing cones differ from that of RPE cells facing rods in a manner that may explain macular susceptibility and pathogenesis of AMD.
The retina of NRL knock-out (NRL-ko) mouse is composed of cone-like photoreceptors, while the retina of wild type (WT) mouse contains mainly rod photoreceptors. RPE cells were harvested from eyes of both WT and NRL-ko mice (6 weeks old). RNA samples were hybridized to Illumina MouseWG-6 v2.0 whole-genome array. After applying filters, including a fold change of 1.7, and dynamic statistical stringency criteria iteratively modified to obtain a manageable list size, a list of 108 genes was generated. From this list, the expression of 25 genes of special interest was validated using Nanostring's nCounter technology.
Several genes that were up regulated in RPE facing cones were previously reported to be associated with macular degenerations when mutated. Genes coding for proteins serving along the phagocytosis process, from binding down to degradation, were up regulated, suggesting a unique phagocytosis process for shed cone outer segment compared to that of rods. Several genes coding for proteins serving in the complement system were altered in a manner consistent with shift in balance toward the classical pathway. Several other genes were altered, including genes involved in cellular adhesions, protection from oxidation, visual transduction and retinol metabolism.
We show that the transciptome of RPE cells can be modulated by the photoreceptors located adjacent to them. Some of the genes have relevance to the physiology of RPE-photoreceptors interactions and others may be of relevance to AMD pathogenesis, including genes coding for proteins of the complement system. We suggest that gene expression of RPE cells facing cones can explain, at least partially, macular susceptibility to age related lesions.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only