title: UV-induced retinal proteome changes in the rat model of age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD.
authors.affiliation: University of Rijeka, Department of Biotechnology, Radmile Matejčić 2, HR-51000 Rijeka, Croatia; University of Rijeka, Centre for high-throughput technologies, Radmile Matejčić 2, HR-51000 Rijeka, Croatia. Electronic address: sandrakp@biotech.uniri.hr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljević Pavelić
authors.affiliation: University of Rijeka, Department of Biotechnology, Radmile Matejčić 2, HR-51000 Rijeka, Croatia; University of Rijeka, Centre for high-throughput technologies, Radmile Matejčić 2, HR-51000 Rijeka, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Klobučar
authors.affiliation: University of Rijeka, Department of Biotechnology, Radmile Matejčić 2, HR-51000 Rijeka, Croatia; University of Rijeka, Centre for high-throughput technologies, Radmile Matejčić 2, HR-51000 Rijeka, Croatia.
authors.forename: Mirela
authors.initials: M
authors.lastname: Sedić
authors.affiliation: The Institute for Medical Research and Occupational Health, Ksaverska cesta 2, POB 291, HR-10001 Zagreb, Croatia.
authors.forename: Vedran
authors.initials: V
authors.lastname: Micek
authors.affiliation: Functional Genomics Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Gehrig
authors.affiliation: Functional Genomics Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grossman
authors.affiliation: University of Rijeka, Department of Biotechnology, Radmile Matejčić 2, HR-51000 Rijeka, Croatia; University of Rijeka, Centre for high-throughput technologies, Radmile Matejčić 2, HR-51000 Rijeka, Croatia.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Pavelić
authors.affiliation: University of Applied Sciences Velika Gorica, Zagrebačka cesta 5, Velika Gorica 10410, Croatia.
authors.forename: Božidar
authors.initials: B
authors.lastname: Vojniković
keywords: Age-related macular degeneration; Interphotoreceptor matrix; Oxidative stress; Proteomics; Retinal pigment epithelium; UV irradiation