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Y.-H. Chen, W. Dailey, M. Cheng, K. A. Drenser; Effect of Ndp Treatment After Neurotoxic Injury in the Rat Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3141.
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Stimulation of the Wnt pathway has been shown to increase retinal neural progenitor cells in injured retina. We sought to evaluate the effect of a retina specific Wnt ligand, norrin, for its effects on injured retina.
Four-week-old male Sprague-Dawley rats were treated with phosphate buffered saline (PBS), NMDA, or NMDA+ norrin. Eighteen hours after receiving intravitreal injections of 400 nmol of NMDA, the treatment eyes received intravitreal injections of 125ng NDP and the untreated eyes received intravitreal PBS injections. Control eyes were injected with PBS only at each experimental time point. Tissues were fixed at 1, 2, 4 and 7 days after the first injection (PBS in control and NMDA in study group). The eyes were sectioned, and immunolabeled with Chx10 and Pax 6 to evaluate the presence of retinal neural progenitor cells.
NMDA injured retina resulted in increased numbers of progenitor cells. Many of these cells co-expressed Chx10 and Pax 6 compared to the PBS treated eyes at day 7. A significant difference was not noted at days 1, 2, or 4. Eyes treated with NMDA+ norrin also showed a significant increase in retinal neural progenitor cells compared to PBS only eyes. However, a statistically significant difference was not seen between eyes treated with NMDA alone and eyes treated with both NMDA+ norrin at day 7.
Our preliminary results showed that single NDP treatment did not significantly increase retinal progenitors in NMDA damaged retina at day 7. This may have been due to the use of a relatively high dose of NMDA used to induce neurotoxic injury or a short half life of the NDP after injection into the retina. Therefore, we have initiated further studies to evaluate the effect of multiple injections with NDP and a longer time course.
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