The retina is a highly differentiated CNS tissue with high energy demand to support constant regeneration. Many retinal diseases are linked to perturbed mitochondrial function which leads to photoreceptor atrophy and neovascularization. Comparatively little is known about the functional genomics of the retina, which does not feature in the current GTEx database.
AIMS
To begin to understand the functional genomics in the context of other tissues especially brain, we aimed to determine the similarity of the retinal transcriptome to other body tissues; and detect co-transcribed gene modules that are specific to the retina.
METHODS
Gene expression for all GTEx tissues was clustered with expression data from 50 publicly available post-mortem retinae [1]. Raw reads for the frontal cortex were mapped and quantified as for the retinal RNAseq. Differential expression analysis was performed with edgeR; and co-expressed modules in each tissue were identified separately using WGCNA and annotated by most abundant GO term using topGO. Jaccard co-efficients were calculated for gene overlap in all module pairs across tissues.
RESULTS
Retinal gene expression was most similar to the pituitary and brain consistent with the CNS origin of this tissue. DEGs were quantified, and independently-identified retinal transcripts [2] were found to drive tissue separation, mitigating the potential for large batch effects. 6,574 genes were highly expressed in both retina and frontal cortex, which formed 17 and 16 clusters respectively. There was substantial genic overlap in these modules, however retinal modules were enriched for GO terms related to neuronal development, dendrite maintenance and response to glucose and heat. Terms enriched only in retinal modules related to histone methylation, ion transport and biomolecule sysnthesis – reflecting the heightened stress load and regenerative activity of this tissue. These findings in healthy retina will support our research into rare macular degeneration [3].