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Long-term exposure to ultraviolet (UV) radiation is associated with pathological alterations of the retinal pigment epithelium (RPE). It has been indicated that Cortistatin (CST) and somatostatin (SST) are able to inhibit the neurodegeneration of the RPE associated with diabetic retinopathy and retinal ischemia via activation of SST receptors (SSTRs). To the best of our knowledge, the present study indicated for the first time that treatment with UV‑A (30 and 60 min) causes an increase of CST expression, rather than SST, which was linked with the upregulation of STTR3,4,5 subtype receptor gene expression levels. The study revealed that: i) SST and CST mRNA expression were both detected under basal conditions in a human retinal pigment epithelial cell line (Arpe‑19); ii) SST expression remained constant from baseline to 1 h of UV‑A treatment; iii) CST mRNA expression levels were 80 times increased compared with time 0 and after 30 min of exposition to ultraviolet irradiation; iv) SSTR1, SSTR2 mRNA and low levels of SSTR4 were expressed in basal conditions, whereas SSTR3 and SSTR5 mRNA were not detected under the same conditions; and v) only SSTR3, SSTR4 and SSTR5 were overexpressed after UV‑A treatment, although in a different way. In conclusion, the findings provide reasonable evidence to support the pathophysiological role of the CST/SST/SSTRs system in the adaptive response of the RPE exposed to UV‑A radiation.

Pathological alterations to the retinal pigment epithelium underlie several eye diseases, which lead to visual impairment and even blindness. Exposure to ultraviolet (UV) radiation is associated with some skin and ocular pathologies; UV radiation may induce DNA breakdown and cause cellular damage through the production of reactive oxygen species (ROS), thus leading to programmed cell death. The present study aimed to investigate the production of ROS and the gene expression levels of anti‑ and proapoptotic proteins [B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and caspase‑3] in human retinal pigment epithelial cells (ARPE‑19) treated with UV‑A for 5 h consecutively. The results demonstrated that prolonged exposure to UV‑A induced: i) Cell death, the decrease in cell viability was time‑dependent and reached statistical significance after 3 h; ii) a significant and substantial increase in ROS levels that remained constant for the duration of the experiment, the levels were significantly increased after 1 h of exposure; iii) an activation of apoptotic genes (Bax and caspase‑3) after 1 h of treatment, which was accompanied by a decrease in the anti‑apoptotic gene Bcl‑2; and iv) a loss of apoptotic signals and a rapid decrease in cellular viability after 3 h of consecutive treatment. These processes may trigger necrosis, which was observed in the cells following treatment with UV‑A for 5 consecutive hours. In conclusion, the present study is the first, to the best of our knowledge, to provide in vitro evidence regarding the sequence of events that underlie the cellular damage induced by prolonged UV‑A radiation, starting from the first 30 min of treatment. UV‑A radiation resulted in the activation of apoptotic events, and subsequently led to irreversible cell necrosis.