Adalimumab reduces photoreceptor cell death in a mouse model of retinal degeneration
EntityUAM. Departamento de Biología Molecular
PublisherNature Publishing Group
10.1038/srep11764Scientific Reports 5 (2015): 11764
Funded byThis work was supported by the European Regional Development Fund, Institute of Health Carlos III, PI12/0481, SAF2013-41059-R and SAF2013-41945 from the Spanish Ministry of Economy and Competitiveness (MEC). CIBERER is an initiative of the Institute of Health Carlos III from the MEC. Regina Rodrigo has a research-contract SNS Miguel Servet (CP09/118) from Institute of Health Carlos III
ProjectGobierno de España. PI12/0481; Gobierno de España. SAF2013-41059-R; Gobierno de España. SAF2013-41945
SubjectsAdalimumab; Inflammation; Retinitis pigmentosa; Photoreceptor; Biología y Biomedicina / Biología
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Growing evidence suggests that inflammation is involved in the progression of retinitis pigmentosa (RP) both in patients and in animal models. The aim of this study was to investigate the effect of Adalimumab, a monoclonal anti-TNFα antibody, on retinal degeneration in a murine model of human autosomal recessive RP, the rd10 mice at postnatal day (P) 18. In our housing conditions, rd10 retinas were seriously damaged at P18. Adalimumab reduced photoreceptor cell death, as determined by scoring the number of TUNEL-positive cells. In addition, nuclear poly (ADP) ribose (PAR) content, an indirect measure of PAR polymerase (PARP) activity, was also reduced after treatment. The blockade of TNFα ameliorated reactive gliosis, as visualized by decreased GFAP and IBA1 immunolabelling (Müller cell and microglial markers, respectively) and decreased up-regulation of TNFα gene expression. Adalimumab also improved antioxidant response by restoring total antioxidant capacity and superoxide dismutase activity. Finally, we observed that Adalimumab normalized energetic and metabolic pattern in rd10 mouse retinas. Our study suggests that the TNFα blockade could be a successful therapeutic approach to increase photoreceptor survival during the progression of RP. Further studies are needed to characterize its effect along the progression of the disease
Google Scholar:Martínez-Fernández de la Cámara, Cristina - Hernández-Pinto, Alberto M. - Olivares-González, Lorena - Cuevas-Martín, Carmen - Sánchez-Aragó, María - Hervás, David - Salom, David - Cuezva Marcos, José Manuel - De La Rosa, Enrique J. - Millán, José M. - Rodrigo, Regina
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Soldevilla, Beatriz; Cuevas-Martín, Carmen; Ibáñez, Clara; Santacatterina, Fulvio; Alberti, María A.; Simó, Carolina; Casasnovas, Carlos; Márquez-Infante, Celedonio; Sevilla, Teresa; Pascual Pascual, Samuel Ignacio; Sánchez-Aragó, María; Espinos, Carmen; Palau, Francesc; Cuezva Marcos, José Manuel