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Gregory H. Grossman, Gayle J. Pauer, Brent A. Bell, Stephanie A. Hagstrom; Dark-rearing Causes a Delay of Photoreceptor Cell Death in tulp1-/- Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1841.
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It has been shown that dark-rearing attenuates retinal degeneration (RD) in mice carrying a mutation in the gene that encodes Tub, the founding-member of the tubby-like proteins (Tulps). We sought to test whether RD could be slowed in tulp1-/- mice by rearing the animals in the dark.
Wild-type (wt) and tulp1-/- mice were born and raised in either a 12 hr on and 12 hr off bright light environment or in constant darkness. At P21 and P30, a histological evaluation of photoreceptor cell layer thickness was conducted on fixed retinal sections along the superior-inferior plane. In addition, we used immunohistochemistry to evaluate the effect of dark-rearing on two compartment-specific defects of tulp1-/- mice, a protein transport disruption in the inner segment and a ribbon synapse defect in the terminal.
In dark-reared tulp1-/- mice at P21, the outer nuclear layer (ONL) was 20% thicker as compared to tulp1-/- mice raised in cyclic light (50.00 µm ± .64 SEM vs. 40.08 µm ± 2.22 SEM, p=0.0079), indicating a significant retention of photoreceptor cells. As anticipated, dark-rearing had no effect on wt mice at P21 (53.38 µm ± 2.26 SEM vs. 53.68 µm ± 1.74 SEM, p=0.916). At this age, dark-rearing did not appear to affect the rhodopsin trafficking deficiency or the synaptic malformation associated with tulp1-/- mice. At P30, dark-rearing did not show a significant retention in the thickness of the ONL of tulp1-/- mice as compared to tulp1-/- mice raised under normal lighting conditions (24.63 µm ± 1.34 SEM vs. 22.09 µm ± 1.98 SEM, p=0.3121).
The rapid loss of photoreceptors is delayed but not prevented by dark-rearing tulp1-/- mice, suggesting that activation of phototransduction accelerates photoreceptor cell death in this mutant mouse model. Although the exact mechanism underlying the delay in photoreceptor cell loss by raising tulp1-/- mice in constant darkness remains unclear, this data provides evidence that reduced light exposure may delay RD in patients with TULP1 mutations.
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