PEDF peptides promote photoreceptor survival in rd10 retina models
| Autor: | Enrique J. de la Rosa, Susan Vitale, Andrés de la Rocha-Muñoz, Alberto M. Hernández-Pinto, Federica Polato, Preeti Subramanian, S. Patricia Becerra |
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| Přispěvatelé: | National Eye Institute (US), Ministerio de Economía y Competitividad (España), American Society for Biochemistry and Molecular Biology, Hernández-Pinto, Alberto M., Polato, Federica, Vitale, Susan, De la Rosa, Enrique J., Becerra, S. Patricia, Hernández-Pinto, Alberto M. [0000-0001-6658-5054], Polato, Federica [0000-0002-7713-8476], Vitale, Susan [0000-0002-5972-6848], De la Rosa, Enrique J. [0000-0001-9984-9706], Becerra, S. Patricia [0000-0002-0646-9729] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Retinal degeneration
Cell Survival Blotting Western Photoreceptor cell Article Cellular and Molecular Neuroscience chemistry.chemical_compound Mice PEDF medicine In Situ Nick-End Labeling Animals Nerve Growth Factors Outer nuclear layer Eye Proteins Fluorescent Antibody Technique Indirect Serpins Retina biology Chemistry Retinal Degeneration Retinal medicine.disease Sensory Systems eye diseases Peptide Fragments Recombinant Proteins Cell biology Mice Inbred C57BL Ophthalmology Disease Models Animal medicine.anatomical_structure Intravitreal Injections biology.protein sense organs Ex vivo Neurotrophin Photoreceptor Cells Vertebrate |
| Zdroj: | Exp Eye Res Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 24 p. 2 fig. The purpose of the study is to evaluate the protective properties of PEDF peptide fragments on rd10 mouse models of retinal degeneration ex vivo. Human recombinant PEDF and synthetic peptides were used. Rd10 retinal explants as well as wild-type retinal explants treated with zaprinast to mimic the rd10 photoreceptor cell death were employed. PEDF protein was intravitreally administered into rd10 mice. Outer nuclear layer thickness measurements in retinal sections, TUNEL labeling in retinal explants, western blots and immunofluorescence with retinal samples were performed. PEDF protein levels in the RPE of rd10 mice decreased with age (P15 - P25). Levels of PEDF receptor PEDF-R declined in the photoreceptor inner segments from rd10 relative to wild-type mice at P25. PEDF administration increased the outer nuclear layer thickness of rd10 retinas in vivo and decreased the number of TUNEL+ nuclei of photoreceptors in rd10 retinal explant cultures, both relative to untreated controls. Peptides containing the PEDF neurotrophic region decreased the number of TUNEL+ photoreceptors in both rd10 and zaprinast-induced cell death ex vivo models, while peptides without the neurotrophic region and/or lacking affinity for PEDF-R were ineffective in protecting photoreceptors. Thus, retinal explants are a valuable system to evaluate PEDF activity. Short peptides with the photoreceptor-protective property of PEDF may prove useful for the development of therapeutic agents for photoreceptor protection in retinal degenerations. This work was supported in part by the Intramural Research Program of the National Eye Institute, NIH, U.S.A. [Project #EY000306 to SPB], and by Ministerio de Economía y Competitividad, Spain (Grants SAF2016-75681-R and CSD2010-00045 to EJdlR), American Society for Biochemistry and Molecular Biology USA (PROLAB award to AMHP). |
| Databáze: | OpenAIRE |
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