Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration

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 autoso...

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Bibliographic Details
Authors: Martínez Fernández de la Cámara, Cristina, Hernández Pinto, Alberto M., Olivares González, Lorena, Cuevas Martín, Carmen, Sánchez Aragó, María, Hervás Marín, David, Salom Alonso, David, Cuezva Marcos, José Manuel, de la Rosa, Enrique J., Millán, José María, Rodrígo, Regina
Format: article
Publication Date:2015
Country:España
Institution:Universidad Católica de Valencia San Vicente Mártir
Repository:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Language:English
OAI Identifier:oai:riucv.ucv.es:20.500.12466/3692
Online Access:http://hdl.handle.net/20.500.12466/3692
Access Level:Open access
Keyword:Adalimumab
Inflammation
Retinitis pigmentosa
Photoreceptor
3201.09 Oftalmología
3209 Farmacología
Description
Summary: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.

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