Abstract
BackgroundRetinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration has been attributed to a wide variety of causes, such as disruption of genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the retina. The molecular pathogenesis of the biological events in retinal degeneration is unclear; however, the molecular basis of the retinal pathological defect can be potentially determined by gene-expression profiling of the whole retina. In the present study, we analyzed the differential gene expression profile of the retina from a wild-type zebrafish and phosphodiesterase 6c (pde6c) mutant.ResultsThe datasets were downloaded from the Sequence Read Archive (SRA), and adaptors and unbiased bases were removed, and sequences were checked to ensure the quality. The reads were further aligned to the reference genome of zebrafish, and the gene expression was calculated. The differentially expressed genes (DEGs) were filtered based on the log fold change (logFC) (±4) and p-values (p < 0.001). We performed gene annotation (molecular function [MF], biological process [BP], cellular component [CC]), and determined the functional pathways Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for the DEGs. Our result showed 216 upregulated and 3527 downregulated genes between normal and pde6c mutant zebrafish. These DEGs are involved in various KEGG pathways, such as the phototransduction (12 genes), mRNA surveillance (17 genes), phagosome (25 genes), glycolysis/gluconeogenesis (15 genes), adrenergic signaling in cardiomyocytes (29 genes), ribosome (20 genes), the citrate cycle (TCA cycle; 8 genes), insulin signaling (24 genes), oxidative phosphorylation (20 genes), and RNA transport (22 genes) pathways. Many more of all the pathway genes were down-regulated, while fewer were up-regulated in the retina of pde6c mutant zebrafish.ConclusionsOur data strongly indicate that, among these genes, the above-mentioned pathways’ genes as well as calcium-binding, neural damage, peptidase, immunological, and apoptosis proteins are mostly involved in the retinal and neural degeneration that cause abnormalities in photoreceptors or retinal pigment epithelium (RPE) cells.
Highlights
Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world
A wide variety of causes have been attributed to retinal degeneration, such as disruption of the genes involved in phototransduction, biosynthesis, folding of the rhodopsin molecule, and the structural support of the retina [4]
Differential gene expression analysis We discovered 216 up-regulated and 3527 downregulated differentially expressed genes (DEGs) in the pde6c mutant conditions
Summary
Retinal degenerative diseases affect millions of people and represent the leading cause of vision loss around the world. Retinal degeneration is retinopathy that consists of the deterioration of the retina due to the progressive death of its cells [1] It is a common cause of blindness, and it can result from mutations in a large variety of structural and enzymatic proteins of the photoreceptors [2]. Humans harboring loss-offunction PDE6b mutations develop RP, progressing to total blindness as a function of age [9, 10] This mutation has been predicted to cause a frameshift in the coding sequence and result either in a truncated pde6c or degradation of pde6c mRNA through nonsense-mediated decay; it affects both cone and rod photoreceptors [7]. Understanding which genes are perturbed in the photoreceptor degeneration could pave the way for the identification of biomarkers as potential predictors of disease onset, as well as elucidating the pathways involved in the degenerative process, as the zebrafish as a model organism that allows rapid screening of a multitude of substances and therapeutic approaches
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