Retinal degeneration in two lines of transgenic S334ter rats

Abstract

Keywords:retinal degeneration rodent remodeling apoptosis protein kinase C calbindin recoverin parvalbumin transducin a b s t r a c t 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 SpragueeDawley) 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 1e2 layers remaining at P30, and only cones left at P60. Line-5 had 4e5 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.

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

“…All evidence indicates that as the degeneration of rod bipolar cells progresses, they display early retraction and loss of dendrites ( Fig. 5CeF) Cuenca et al, 2004Cuenca et al, , 2005bMartinez-Navarrete et al, 2011;Strettoi et al, 2004). After photoreceptor death, bipolar cells initially retract their dendrites ( Fig.…”

Role of Müller cells in cone mosaic rearrangement in a rat model of retinitis pigmentosa

“…Several laboratories have previously reported changes in both the photoreceptors and the inner retina of the S334ter-rat model of RP (Anderson et al, 2002;Hombrebueno et al, 2010;Li et al, 2010;Martinez-Navarrete et al, 2010;Ray et al, 2010). Other changes include cones' migration to the inner nuclear layer (Lin et al, 2009) and shortening and disorganization of segments and axons (Figs.…”

“…2). Previous studies examined rod cell deaths in the vertical sections of homozygous (Li et al, 2010) and heterozygous animals of S334ter-line-3 rat retinas (Liu et al, 1999;Martinez-Navarrete et al, 2010;Ray et al, 2010;Sagdullaev et al, 2003). Vertical-section studies only allow us to look at the thickness of the ONL and to observe how it decreases as the disease progresses.…”

“…The primary pathological event of this disease is the death of rods because of genetic mutations. Studies in animal models of RP have shown that rod degeneration leads to cone (Li et al, 2010;Lin et al, 2009) and inner-retinal (Gargini et al, 2007;Jones and Marc, 2005;Marc and Jones, 2003;Martinez-Navarrete et al, 2010;Ray et al, 2010;Strettoi et al, 2004) remodeling, resulting in abnormal circuitry. In addition, rod degeneration frequently results in the death of cones, although the extent of their apoptosis varies across patients (Hartong et al, 2006;Ripps, 2002) and animal models (Carter-Dawson et al, 1978;Jimenez et al, 1996;LaVail et al, 1998).…”

Correlation between SD‐OCT, immunocytochemistry and functional findings in an animal model of retinal degeneration

“…By P28, the ONL had lost approximately 40% of its cells (Machida et al, 2000). At this age, we observed rhodopsin mislocated along the remaining rod photoreceptor cells, which is a regular trait in RP diseases (Cuenca et al, 2004(Cuenca et al, , 2005Barhoum et al, 2008;Martinez-Navarrete et al, 2011). By P180, the ONL had fewer than two rows of cells remaining, and they were essentially cones.…”