Systemic taurine treatment affords functional and morphological neuroprotection of photoreceptors and restores retinal pigment epithelium function in RCS rats
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
Affiliations
Ana Martínez-Vacas
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Johnny Di Pierdomenico
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Alejandro Gallego-Ortega
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Francisco J. Valiente-Soriano
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Manuel Vidal-Sanz
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Serge Picaud
Sorbonne Universités, INSERM, CNRS, Institut de la Vision, Paris, France
María Paz Villegas-Pérez
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain
Diego García-Ayuso
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca), Murcia, Spain; Corresponding author. Laboratorio de Oftalmología Experimental, Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca, Edificio LAIB Planta 5a, Carretera Buenavista s/n, 30120 El Palmar, Murcia, Spain.
The aim of our work was to study whether taurine administration has neuroprotective effects in dystrophic Royal College of Surgeons (RCS) rats, suffering retinal degeneration secondary to impaired retinal pigment epithelium phagocytosis caused by a MERTK mutation. Dystrophic RCS-p + female rats (n = 36) were divided into a non-treated group (n = 16) and a treated group (n = 20) that received taurine (0.2 M) in drinking water from postnatal day (P)21 to P45, when they were processed. Retinal function was assessed with electroretinogram. Retinal morphology was assessed in cross-sections using immunohistochemical techniques to label photoreceptors, retinal microglial and macroglial cells, active zones of conventional and ribbon synaptic connections, and oxidative stress. Retinal pigment epithelium function was examined using intraocular fluorogold injections. Our results document that taurine treatment increases taurine plasma levels and photoreceptor survival in dystrophic rats. The number of photoreceptor nuclei rows at P45 was 3–5 and 6–11 in untreated and treated animals, respectively. Electroretinograms showed increases of 70% in the rod response, 400% in the a-wave amplitude, 30% in the b-wave amplitude and 75% in the photopic b-wave response in treated animals. Treated animals also showed decreased numbers of microglial cells in the outer retinal layers, decreased glial fibrillary acidic protein (GFAP) expression in Müller cells, decreased oxidative stress in the outer and inner nuclear layers and improved maintenance of synaptic connections. Treated animals showed increased FG phagocytosis in the retinal pigment epithelium cells. In conclusion, systemic taurine treatment decreases photoreceptor degeneration and increases electroretinographic responses in dystrophic RCS rats and these effects may be mediated through various neuroprotective mechanisms.
