title: Adalimumab Reduces Photoreceptor Cell Death in A Mouse Model of Retinal Degeneration.
abstract: 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.
authors.affiliation: Grupo de Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Fernández de la Cámara
authors.affiliation: 3D Lab (Desarrollo, Diferenciación &Degeneración), Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Hernández-Pinto
authors.affiliation: 1] Grupo de Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe, Valencia, Spain [2] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Olivares-González
authors.affiliation: 1] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain [2] Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas-Martín
authors.affiliation: 1] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain [2] Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Aragó
authors.affiliation: Unidad de Bioestadística, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hervás
authors.affiliation: Servicio de Oftalmología, Hospital de Manises, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Salom
authors.affiliation: 1] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain [2] Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Cuezva
authors.affiliation: 3D Lab (Desarrollo, Diferenciación &Degeneración), Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: de la Rosa
authors.affiliation: 1] Grupo de Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe, Valencia, Spain [2] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain [3] Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.affiliation: 1] Grupo de Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe, Valencia, Spain [2] CIBER de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Rodrigo
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004734:Energy Metabolism / Q000187:drug effects; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D011065:Poly(ADP-ribose) Polymerases; D000068879:Adalimumab