title: Retinal degeneration in two lines of transgenic S334ter rats.
abstract: Aim of this study was to examine synaptic connectivity changes in the retina and the location and rate of apoptosis in transgenic S334ter line-3 and line-5 rats with photoreceptor degeneration. Heterozygous S334ter-line-3 and line-5 at P11-13, P30, P60, P90 and several control non-dystrophic rats (Long Evans and Sprague-Dawley) at P60, were studied anatomically by immunohistochemistry for various cell and synaptic markers, and by PNA and TUNEL label.- S334ter line-3 exhibited the fastest rate of degeneration with an early loss of photoreceptors, with 1-2 layers remaining at P30, and only cones left at P60. Line-5 had 4-5 layers left at P30, and very few rods left at P60-90. In both lines, horizontal cell processes (including dendrites and axon) were diminished at P11-13, showing gaps in the outer plexiform layer (OPL) at P60, and at P90, almost no terminal tips could be seen. Bipolar cells showed a retraction of their dendrites forming clusters along the OPL. Synaptic terminals of A-II amacrine cells in the IPL lost most of their parvalbumin-immunoreactivity. The apoptosis rate was different in both lines. Line-3 rats showed many photoreceptors affected at P11, occupying the innermost part of the outer nuclear layer. Line-5 showed a lower number of apoptotic cells within the same location at P13. In summary, the S334ter line-3 rat has a faster progression of degeneration than line-5. The horizontal and bipolar terminals are already affected at P11-P13 in both models. Apoptosis is related to the mutated rhodopsin transgene; the first photoreceptor cells affected are those close to the OPL.
authors.affiliation: Department of Physiology, Genetics, Microbiology, University of Alicante, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Martinez-Navarrete
authors.forename: M J
authors.initials: MJ
authors.lastname: Seiler
authors.forename: R B
authors.initials: RB
authors.lastname: Aramant
authors.forename: L
authors.initials: L
authors.lastname: Fernandez-Sanchez
authors.forename: I
authors.initials: I
authors.lastname: Pinilla
authors.forename: N
authors.initials: N
authors.lastname: Cuenca
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D064026:Calbindins; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D008297:Male; D010320:Parvalbumins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D017729:Presynaptic Terminals / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D051603:Recoverin / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000378:metabolism; D051248:Retinal Horizontal Cells / Q000378:metabolism / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015293:Transducin / Q000378:metabolism
chemical_list: D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D051603:Recoverin; D011493:Protein Kinase C; D015293:Transducin