Abstract
Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes’ profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.
Highlights
Oxidative stress, recently defined as “a state where oxidative forces exceed the antioxidant systems due to loss of the balance between them”, represents one of the principal inductors of lifestyle-related and genetic diseases [1]
We realized a whole RNA-seq experiment on retinal pigment epithelium (RPE) cells treated with A2E, considering two time points (3 h and 6 h) after the basal one
differentially alternative spliced (DAS) genes, with many highlighted sub-pathways, which could depict a more detailed scenario determined by induced oxidative stress
Summary
Recently defined as “a state where oxidative forces exceed the antioxidant systems due to loss of the balance between them”, represents one of the principal inductors of lifestyle-related and genetic diseases [1]. The most relevant risk factor associated with AMD etiopathogenesis is represented by high levels of oxidative stress damaging the macula, generally induced by production of advanced glycation end products (AGE) and exposition to environmental factors [7]. The majority of such effects are exerted by dysregulation of vascular endothelial growth factor (VEGF), impairment proteins and organelles clearance and glial cell dysfunctions [8]. Oxidative damage is considered the first cause of cone apoptosis and progressive vision loss [14]
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