Purpose: The purpose of this study was to study the effect of minocycline and several neurotrophic factors, alone or in combination, on photoreceptor survival and macro/microglial reactivity in two rat models of retinal degeneration. Methods: P23H-1 (rhodopsin mutation), Royal College of Surgeon (RCS, pigment epithelium malfunction), and age-matched control rats (Sprague-Dawley and Pievald Viro Glaxo, respectively) were divided into three groups that received at P10 for P23H-1 rats or P33 for RCS rats: (1) one intravitreal injection (IVI) of one of the following neurotrophic factors: ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), or basic fibroblast growth factor (FGF2); (2) daily intraperitoneal administration of minocycline; or (3) a combination of IVI of FGF2 and intraperitoneal minocycline. All animals were processed 12 days after treatment initiation. Retinal microglial cells and cone photoreceptors were immunodetected and analyzed qualitatively in cross sections. The numbers of microglial cells in the different retinal layers and number of nuclei rows in the outer nuclear layer (ONL) were quantified. Results: IVI of CNTF, PEDF, or FGF2 improved the morphology of the photoreceptors outer segment, but only FGF2 rescued a significant number of photoreceptors. None of the trophic factors had qualitative or quantitative effects on microglial cells. Minocycline treatment reduced activation and migration of microglia and produced a significant rescue of photoreceptors. Combined treatment with minocycline and FGF2 had higher neuroprotective effects than each of the treatments alone. Conclusions: In two animal models of photoreceptor degeneration with different etiologies, minocycline reduces microglial activation and migration, and FGF2 and minocycline increase photoreceptor survival. The combination of FGF2 and minocycline show greater neuroprotective effects than their isolated effects.
Purpose: The purpose of this study was to study the effect of minocycline and several neurotrophic factors, alone or in combination, on photoreceptor survival and macro/microglial reactivity in two rat models of retinal degeneration. Methods:P23H-1 (rhodopsin mutation), Royal College of Surgeon (RCS, pigment epithelium malfunction), and age-matched control rats (Sprague-Dawley and Pievald Viro Glaxo, respectively) were divided into three groups that received at P10 for P23H-1 rats or P33 for RCS rats: (1) one intravitreal injection (IVI) of one of the following neurotrophic factors: ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), or basic fibroblast growth factor (FGF2); (2) daily intraperitoneal administration of minocycline; or (3) a combination of IVI of FGF2 and intraperitoneal minocycline. All animals were processed 12 days after treatment initiation. Retinal microglial cells and cone photoreceptors were immunodetected and analyzed qualitatively in cross sections. The numbers of microglial cells in the different retinal layers and number of nuclei rows in the outer nuclear layer (ONL) were quantified. Results: IVI of CNTF, PEDF, or FGF2 improved the morphology of the photoreceptors outer segment, but only FGF2 rescued a significant number of photoreceptors. None of the trophic factors had qualitative or quantitative effects on microglial cells. Minocycline treatment reduced activation and migration of microglia and produced a significant rescue of photoreceptors. Combined treatment with minocycline and FGF2 had higher neuroprotective effects than each of the treatments alone. Conclusions: In two animal models of photoreceptor degeneration with different etiologies, minocycline reduces microglial activation and migration, and FGF2 and minocycline increase photoreceptor survival. The combination of FGF2 and minocycline show greater neuroprotective effects than their isolated effects.
Authors: Ana Martínez-Vacas; Johnny Di Pierdomenico; Alejandro Gallego-Ortega; Francisco J Valiente-Soriano; Manuel Vidal-Sanz; Serge Picaud; María Paz Villegas-Pérez; Diego García-Ayuso Journal: Redox Biol Date: 2022-10-14 Impact factor: 10.787
Authors: Fernando Lucas-Ruiz; Caridad Galindo-Romero; Kristy T Rodríguez-Ramírez; Manuel Vidal-Sanz; Marta Agudo-Barriuso Journal: Int J Mol Sci Date: 2019-11-15 Impact factor: 5.923
Authors: Fernando Lucas-Ruiz; Caridad Galindo-Romero; Manuel Salinas-Navarro; María Josefa González-Riquelme; Manuel Vidal-Sanz; Marta Agudo Barriuso Journal: Front Neurosci Date: 2019-10-15 Impact factor: 4.677
Authors: Diego García-Ayuso; Johnny Di Pierdomenico; Manuel Vidal-Sanz; María P Villegas-Pérez Journal: Int J Mol Sci Date: 2019-09-19 Impact factor: 5.923
Authors: Francisco J Valiente-Soriano; Arturo Ortín-Martínez; Johnny Di Pierdomenico; Diego García-Ayuso; Alejandro Gallego-Ortega; Juan A Miralles de Imperial-Ollero; Manuel Jiménez-López; María Paz Villegas-Pérez; Larry A Wheeler; Manuel Vidal-Sanz Journal: Transl Vis Sci Technol Date: 2019-12-16 Impact factor: 3.283
Authors: Francisco J Valiente-Soriano; Johnny Di Pierdomenico; Diego García-Ayuso; Arturo Ortín-Martínez; Juan A Miralles de Imperial-Ollero; Alejandro Gallego-Ortega; Manuel Jiménez-López; M Paz Villegas-Pérez; S Patricia Becerra; Manuel Vidal-Sanz Journal: Int J Mol Sci Date: 2020-09-30 Impact factor: 5.923