title: Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa.
abstract: OBJECTIVE
  Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats.
  
  
  METHODS
  Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors.
  
  
  RESULTS
  In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas.
  
  
  CONCLUSIONS
  In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante Alicante, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Sánchez
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lax
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante Alicante, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Campello
authors.affiliation: Department of Ophthalmology, Aragon Institute for Health Research, Lozano Blesa University Hospital Zaragoza, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pinilla
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of AlicanteAlicante, Spain; Institute Ramón Margalef, University of AlicanteAlicante, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Cuenca
keywords: P23H; astrocytes; gliosis; immunolabeling; müller cells; retinal remodeling