Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks

Abstract

The human eye has several specialized tissues which direct, capture, and pre-process information to provide vision. RNA-seq gene expression analyses have been used extensively, for example, to profile specific eye tissues and in large consortium studies, like the GTEx project, to study tissue-specific gene expression patterning. However, there has not been an integrated study of multiple eye tissues expression patterning with other human body tissues. We have collated current publicly available healthy human RNA-seq datasets and a substantial subset of the GTEx project RNA-seq datasets and processed all in a consistent bioinformatic workflow. We use this fully integrated dataset to probe the relatedness and biological processes between the cornea, retina, RPE-choroid complex, and the rest of the human tissues with differential expression, clustering, and GO term enrichment tools. We also leverage our large collection of retina and RPE-choroid tissues to build the first human weighted gene correlation networks and use them to highlight known biological pathways and eye gene disease enrichment. Finally, we make these data, analyses, and visualizations available via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease

“…In contrast to skin, melanin pigment in RPE was shown to be synthesized prenatally and stored in melanosomes throughout life, while tyrosinase activity in adult RPE remained controversial (57,58). Our study provides additional insight: our query of EyeIntegration data (32) found TYR expressed in adult human RPE, which may influence melanin production and its protective function in retina. Therefore, variants in or near TYR may represent risk factors beyond fetal melanin production.…”

“…These findings support the idea that the credible set captures the essential signal. (4) We queried the 17 genes overlapping the two loci for expression in eye tissue and cells in EyeIntegration summary data (43). We found five and three genes, respectively, expressed in adult retina and adult RPE cells ( CD46, PLXNA2, CR1, CD34, CD55 ; TYR, GRM5, NOX4 ; Figure S7-S8 ).…”

“…For each significant eQTL in EyeGEx, we conducted colocalization analyses using eCAVIAR (31) to evaluate whether the observed early AMD association signal colocalized with the variants’ association with gene expression. (4) Retinal expression: We queried the EyeIntegration database to evaluate genes in the relevant loci for expression in fetal or adult retina or RPE cells (32). (5) Animal model: We queried the Mouse Genome Informatics (MGI) database (www.informatics.jax.org) for each gene in the relevant loci for relevant eye phenotypes in mice (33).…”

TRPM3_miR-204: a complex locus for eye development and disease

“…Recently, TRPM3 has been immuno-localized to subdomains of the apical plasma membrane of human fetal RPE cells with particular enrichment at apical tight junctions and the base of primary cilia [136]. RNA sequencing confirms that TRPM3 is more abundant in human RPE tissue and cell lines and a lens stem cell line than in retinal or corneal derived cells [137,138].…”

Humic-acid-driven escape from eye parasites revealed by RNA-seq and target-specific metabarcoding

“…Most of the current (and limited) information we have on eye immunity comes from mammalian models; we know very little about immune processes in the eye of other taxa [68,69,76,77]. More studies targeting multiple eye tissues [78] are therefore clearly needed to evaluate the "immunopriviliged" status of sh eyes in response to eye parasites.…”