A Morphometric Study of Light-Induced Damage in Transgenic Rat Models of Retinitis Pigmentosa

Abstract

A complex pattern of light-induced damage outcomes was identified in S334ter (sublines 4 and 9) and P23H (sublines 2 and 3) rats. The relative susceptibilities of each subline to damage by light were different, even within the same transgene, but consistent factors included a sensitive region in the superior hemisphere and potentiation by dark-rearing.

Light-induced exacerbation of retinal degeneration in a rat model of Smith–Lemli–Opitz syndrome

“…Intense light exposure (retinal light damage paradigm) was performed essentially as described in detail previously (Organisciak et al, 1996(Organisciak et al, , 1999Vaughan et al, 2003). After 20-24 hr of dark adaptation, control and AY9944-treated animals were light-exposed, either at P28 or P37 (when AY9944-treated animals show little sign of retinal degeneration; Fliesler et al, 1999).…”

“…The methods employed for fixation, embedment, sectioning, and histological analysis of eyes were as previously described (Vaughan et al, 2003;Fliesler et al, 2004). In brief, one eye of each animal, fixed with buffered mixed aldehydes, was dissected into hemispheres such that the vertical meridian from superior to inferior pole became the sectioned face.…”

“…Whereas chronic light exposures are difficult to quantify in human patients, experimental animal models have provided convincing evidence in support of this notion (Radu et al, 2004;Vaughan et al, 2003). Noteworthy in this regard is the recent report by Cideciyan and colleagues (2005), regarding a naturally occurring canine model of retinitis pigmentosa, in which they stated that 'modest light levels, as used in routine clinical practice, dramatically accelerated the neurodegeneration', leading those authors to call for 'a genespecific clinical trial of light reduction in human rhodopsin disease'.…”

Lipid hydroperoxide formation in the retina: correlation with retinal degeneration and light damage in a rat model of Smith–Lemli–Opitz syndrome

“…Note that this represents a time point immediately after the period of intense light exposure (i.e. no 'recovery period'), in contrast to prior studies, where a 2-week recovery period intervened between light exposure and histological analysis (see Organisciak et al, 1996;Vaughan et al, 2003Vaughan et al, , 2005. Remarkably, even at this very early postexposure time point, this same region in light-exposed SLOS rat retinas (Fig.…”

“…More recently, we showed that intense light exposure markedly exacerbates that retinal degeneration, whereas treatment of rats with dimethylthiourea, a hydroxyl radical scavenger and anti-oxidant, prior to light exposure largely protects against the enhancement of degeneration (Vaughan et al, 2005), implicating a free radical mechanism in the degeneration. Herein, we provide evidence that correlates the severity of retinal degeneration in the SLOS rat model, relative to normal albino rats, with accumulated levels of lipid hydroxperoxides (LPOs) in the retina, particularly with intense light exposure.The SLOS rat model was produced as previously described (Fliesler et al, 2004), by treatment of Sprague Dawley (albino) rats with AY9944, a selective inhibitor of 3β-hydroxysterol-Δ 7 -reductase (Dvornik et al, 1963;Givner and Dvornik, 1965 Vaughan et al, 2003 Vaughan et al, , 2005. Rats (6-wk postnatal age, N=4 per group) were darkadapted overnight, and then exposed for 24 hr to intense green light (1700 lux, 490-580 nm) in a temperature-controlled, Plexiglass chamber (kindly provided by D.T.…”