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SF Coulibaly, DK Vaughan, RM Darrow, DT Organisciak; Morphological Comparison of Retinal Light Damage in the P23H and S334ter Mutant Rat Models of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3733.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The rhodopsin P23H and S334ter mutations result in Retinitis Pigmentosa in both humans and transgenic animal disease models. Fast-degenerating P23H line 3 rats are more susceptible to light damage than are normal rats (Coulibaly et al., ARVO 2001). This study compares relative susceptibility between different P23H and S334ter sublines. Methods: Rats from P23H sublines 2 and 3, and from S334Ter sublines 4 and 9, were reared to P60 in cyclic light (CR) or in darkness (DR) and then exposed to 1-8 hr of intense green light starting at 9am. Morphological analysis of the vertical meridian was done 2 wk later. Rod outer segment (ROS) length and outer nuclear layer (ONL) thickness were plotted against location relative to the optic nerve head. Differences between means were tested for significance (p<0.02). Results: Unexposed controls: Compared to normal rats, CR transgenics had shorter ROS and thinner ONLs. Of CR P23H rats, photoreceptor degeneration was faster in subline 3 than in subline 2. Of CR S334ter rats, degeneration was faster in subline 4 than in subline 9; subline 4 degeneration in superior retina outpaced that of inferior retina (superior retina includes the light damage-sensitive area). Intense light exposure reduced superior ROS length in P23H subline 2 and 3 rats and in S334ter subline 9 rats, with little measurable effect in S334ter subline 4 rats. Exposure reduced superior ONL thickness in CR P23H subline 2 and 3 rats only. Exposure did not reduce ONL thickness in either CR S334ter subline 4 or 9 rats, but in DR animals, a reduction was seen. Conclusion: (1) When CR but not exposed to intense light, all 4 transgenic models for RP exhibited retinal degenerations, but to varying extents, as expected (LaVail, unpublished). DR gave somewhat better preserved photoreceptors at age P75, when retinas were collected. (2) In P75 CR P23H rats exposed to intense light at P60, damage was more severe in the faster degenerating subline 3 than in subline 2; but both showed significant damage, and damage was potentiated by DR. (3) In P75 CR S334ter rats exposed to intense light at P60, damage in the slower-degenerating subline 9 was reflected only in shorter ROS (not in thinning of the ONL). When DR, however, ROS loss was potentiated and significant ONL thinning was also observed. (Grant EY01959 to DTO)
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