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

Abstract

The human eye is built from several specialized tissues which direct, capture and pre-process information to provide vision. The gene expression of the different eye tissues has been extensively profiled with RNA-seq across numerous studies. Large consortium projects have also used RNA-seq to study gene expression patterning across many different human tissues, minus the eye. There has not been an integrated study of expression patterns from multiple eye tissues compared with other human body tissues. We have collated all publicly available healthy human eye RNA-seq datasets as well as dozens of other tissues. We use this fully integrated dataset to probe the biological processes and pan expression relationships between the cornea, retina, retinal pigment epithelium (RPE)-choroid complex, and the rest of the human tissues with differential expression, clustering and gene ontology 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. We also have integrated publicly available single-cell RNA-seq data from mouse retina into our framework for validation and discovery. Finally, we make all these data, analyses and visualizations available via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice

“…We identified highest levels of MYRF expression in the RPE/choroid and in the optic nerve, with low levels in other ocular tissues relative to extraocular muscle ( Fig 5 ). These results are consistent with the known role of MYRF in myelination of the optic nerve and relative expression data based on RNAseq experiments in human ocular tissues [55]. A similar pattern of expression was observed in mouse ocular tissues with a 99.5±1.8 fold greater expression in RPE as compared to retina by qRT-PCR.…”

“…In oligodendrocytes, SOX10 and MYRF have been shown to activate dual-specificity phosphatase ( Dusp15 ), which in part contributes to oligodendrocyte differentiation [66]. Intriguingly, Dusp15 is also expressed in fetal RPE [55], warranting a further exploration of this pathway in ocular development.…”

Retinal Gene Distribution and Functionality Implicated in Inherited Retinal Degenerations Can Reveal Disease-Relevant Pathways for Pharmacologic Intervention

“…A recent demonstration of a genetically tiered testing strategy can improve our genetic diagnosis of retinal disease and facilitate treatment [43]. Moreover, the use of weighted whole-genome approaches can reveal candidate eye disease genes [44]. The use of patient-derived induced pluripotent stems cells [45] and the retinal organoid technology [46,47] offer the promise to allow experimentation of disease-associated mutations in a genetically controlled context.…”

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.…”