Comprehensive analysis of gene expression in human retina and supporting tissues

Abstract

<jats:p>Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant forCFH,C3 andCFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.</jats:p>

Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments

“…Different types and functions of the cells in the NR/RPE complex make understanding the overall cholesterol maintenance in the retina diffi cult. Nevertheless, progress has been made, and now we know that the retina obtains cholesterol via local biosynthesis and uptake of blood-borne cholesterol and contains all the genes necessary for independent cholesterol homeostasis (7)(8)(9)(10)(11)(12). The means of cholesterol elimination have also been ascertained and comprise lipoproteinmediated transport to the systemic circulation, metabolism to oxysterols by CYP27A1 and CYP46A1, and PR phagocytosis by the RPE, the retina-specifi c mechanism ( 13,14 ).…”

Genetic Factors Associated With Choroidal Vascular Hyperpermeability and Subfoveal Choroidal Thickness in Polypoidal Choroidal Vasculopathy

“…27 Moreover, recent reports have demonstrated that both genes are expressed in the choroid. 28,29 Although the precise mechanisms are unknown, choroidal thickness might be controlled through inflammatory reactions that involve complement activation.…”

Differential Gene Expression in Age-Related Macular Degeneration

“…To maximize their expression data, Li et al (2014) integrated genetic variation data with expression data generated via RNA-seq. Specifically, they generated genotypes using a SNP chip on peripheral blood from each human eye donor to examine whether or not the previously identified SNPs also associated with ophthalmic diseases (including AMD), and showed allele-specific expression (ASE) in their RNA-seq data.…”

“…Compared with traditional gene expression microarrays, RNA-seq also has a lower frequency of false-positive findings and a higher reproducibility as measured by validation because of less technical variation (Twine et al 2011;Yendrek et al 2012;Potok et al 2013). To date, only two studies have used RNA-seq to study eye tissue (Farkas et al 2013;Li et al 2014). Specifically, Farkas et al (2013) examined retinal tissue from three donors in their 40s with normal phenotype as defined by no known ocular history.…”

“…They identified 116 putative novel genes and 22,000 alternative splice sites. Li et al (2014) studied eight eyes over the age of 60 yr defined as normal by phenotyping the fellow eye by retinal imaging, optical coherence tomography (OCT), and histological examination. Using RNA-seq they were able to show differential expression between the transcriptome of the neural retina and RPE/choroid/sclera.…”