Project description:The principal aim of this work was to investigate the methylation profiles of specific ocular tissues, and compare this profile to matched peripheral blood. Matched human blood and eye tissue were obtained post-mortem (n=8) and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform.
Project description:The normal gene expression profiles of the tissues in the eye are a valuable resource for considering genes likely to be involved with disease processes. This is based on the assumption that transcript abundances in healthy tissue are correlated to the continued health of that tissue. Expression values were compared with publically available EST and RNA-sequencing resources. The estimated gene and exon level abundances are available online on the Ocular Tissue Database.
Project description:The normal gene expression profiles of the tissues in the eye are a valuable resource for considering genes likely to be involved with disease processes. This is based on the assumption that transcript abundances in healthy tissue are correlated to the continued health of that tissue. Expression values were compared with publically available EST and RNA-sequencing resources. The estimated gene and exon level abundances are available online on the Ocular Tissue Database. Ten different tissues were obtained from 6 different individuals and RNA was pooled. The tissues included: retina, optic nerve head (ONH), optic nerve (ON), ciliary body (CB), trabecular meshwork (TM), sclera, lens, cornea, choroid/RPE and iris.
Project description:The eye is an intricate organ with limited representation in large-scale functional genomics datasets. The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions. Genes with disproportionately high fRPE expression are enriched for genes related to inherited ocular diseases. Variants near these fRPE-selective genes explain a larger fraction of risk for both age-related macular degeneration (AMD) and myopia than variants near genes enriched in 53 non-ocular human tissues. Increased mitochondrial oxidation of glutamine by fRPE promoted expression of lipid synthesis genes implicated in AMD. Expression and splice quantitative trait loci (e/sQTLs) analyses revealed shared and metabolic condition-specific loci of each type and several eQTLs not previously described in any tissue. Fine mapping of fRPE e/sQTLs across AMD and myopia genome-wide association data suggests new candidate genes, and mechanisms by which the same common variant of RDH5 contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTLs in a critical ocular cell type to monogenic and complex eye disorders.
Project description:Pediatric adamantinomatous craniopharyngioma (ACP) cyst may be associated with injury to critical neurological structures, such as the hypothalamus, resulting in poor quality of life and shorter lifespan. This work presents evidence that immune actors, both pro-inflammatory and immunomodulatory, and their receptors, are present at unique levels in ACP cyst fluid and tumor tissue, potentially indicating a mechanism underlying cyst growth and tumor invasion of the hypothalamus. Transcriptomic analysis revealed that ACP, when compared to other pediatric brain tumors and nomral brain, harbored overexpression of a number of inflammatory and immunosuppressive genes.