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Clare Corbett, Elizabeth Muckersie, John Forrester, Department of Ophthalmology; The effect of light on retinal structure and the development of EAU in the transgenic spontaneous model of uveitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5369.
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The transgenic model of spontaneous experimental uveitis (EAU) develops retinal inflammation characterized by infiltration of the retina by T-cells, macrophages and dendritic cells. This model was generated by crossing IRBP-HELhi single transgenic mice on a B10.BR background, which express the protein hen egg lysozyme (HEL) as a novel self-antigen in the eye, with the 3A9 strain of mice that express HEL-specific T-cell receptors. The single and double Tg mice both display unusual clinical and histological retinal degenerative disease that includes patchy chorioretinal atrophic lesions, occasional occluded blood vessels and extensive photoreceptor loss in the inferior retina. The mice are negative for the retinal degeneration genes rds, rd1 and rd8.The purpose of this study was to investigate the role of light damage in this retinal degeneration.
To study the effect of ambient lighting conditions, non-transgenic, 3A9, IRBP-HELhi single and double Tg mice were maintained for 30 and 60 days in high lighting (150 lux) or low lighting (5 lux) conditions. Eye health and EAU development were assessed for each genotype and time-point by clinical fundoscopic grading (n=6). Eyes were harvested, SNAP frozen in OCT and 6-8μm sections stained for the presence of macrophages, dendritic cells, B-cells and CD4+ T-cells. Sections were counterstained with haematoxylin and disease severity graded histologically.
Both single IRBP-HELhi Tg and double Tg mice demonstrated inferior retina photoreceptor loss to a similar degree in both the high light and low light conditions. No photoreceptor loss was observed in the non-transgenic or 3A9 mice strains. The clinical EAU scores of the double Tg mice showed no difference between the high and low light conditions at 30 days with active inflammation in both the inferior and superior retina. Inflammatory cells were not observed in the eyes of single IRBP-HELhi Tg mice in any conditions tested.
Photoreceptor loss is a feature in single and double Tg mice in both high and low light conditions. In the IRBP-HELhi single Tg mice photoreceptor loss is not a consequence of immune cell induced damage. As ten percent of transgenic animals have altered phenotypes associated with transgene insertion, the insertion site of the transgene construct in the IRBP-HELhi strain genome may have disrupted genes involved in retinal structure.
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