title: Laser-induced ocular hypertension in adult rats does not affect non-RGC neurons in the ganglion cell layer but results in protracted severe loss of cone-photoreceptors.
abstract: To investigate the long-term effects of laser-photocoagulation (LP)-induced ocular hypertension (OHT) in the innermost and outermost (outer-nuclear and outer segment)-retinal layers (ORL). OHT was induced in the left eye of adult rats. To investigate the ganglion cell layer (GCL) wholemounts were examined at 1, 3 or 6 months using Brn3a-immunodetection to identify retinal ganglion cells (RGCs) and DAPI-staining to detect all nuclei in this layer. To study the effects of LP on the ORL up to 6 months, retinas were: i) fresh extracted to quantify the levels of rod-, S- and L-opsin; ii) cut in cross-sections for morphometric analysis, or; iii) prepared as wholemounts to quantify and study retinal distributions of entire populations of RGCs (retrogradely labeled with fluorogold, FG), S- and L-cones (immunolabeled). OHT resulted in wedge-like sectors with their apex on the optic disc devoid of Brn3a(+)RGCs but with large numbers of DAPI(+)nuclei. The levels of all opsins diminished by 2 weeks and further decreased to 20% of basal-levels by 3 months. Cross-sections revealed focal areas of ORL degeneration. RGC survival at 15 days represented approximately 28% and did not change with time, whereas the S- and L-cone populations diminished to 65% and 80%, or to 20 and 35% at 1 or 6 months, respectively. In conclusion, LP induces in the GCL selective RGCs loss that does not progress after 1 month, and S- and L-cone loss that progresses for up to 6 months. Thus, OHT results in severe damage to both the innermost and the ORL.
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortín-Martínez
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salinas-Navarro
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Francisco Manuel
authors.initials: FM
authors.lastname: Nadal-Nicolás
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez-López
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: García-Ayuso
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bernal-Garro
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Avilés-Trigueros
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain.
authors.forename: María Paz
authors.initials: MP
authors.lastname: Villegas-Pérez
authors.affiliation: Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30100 Murcia, Spain. Electronic address: manuel.vidal@um.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D017075:Laser Coagulation / Q000009:adverse effects*; D009798:Ocular Hypertension / Q000209:etiology / Q000473:pathology*; D055355:Opsins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000528:radiation effects
chemical_list: D055355:Opsins
keywords: Adult albino rat retinal ganglion cells; Displaced amacrine cells; Elevated intraocular pressure; Ganglion cell layer of the retina; Limbar laser photocoagulation; Neuronal degeneration; Ocular hypertension; Outer retinal layers; Photoreceptors loss; Rodent experimental glaucoma model; S-cones L-cones