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T. Miyawaki, A. Uemura, Y. Ueda, S. Yu, Y. Honda, T. Tanabe; The Role of Tlx, Orphan Nuclear Receptor in Developing Mice Retinas . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4522.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We previously reported that Tlx, an orphan nuclear receptor, knockout mouse showed the phenotype of retinal degeneration and optic nerve atrophy. To understand precisely how retinal development is controlled by Tlx, we analyzed the morphological and functional changes in the developing retina of Tlx knockout mice. Methods: The expression pattern of Tlx in the developing retinas was analyzed through the use of lacZ knock-in marker. The histological changes in homozygotic Tlx knockout mice retinas were examined by using light microscopy and functional changes were evaluated by ERG recording. To analyze the molecular mechanisms underling changes in the development and differentiation of Tlx knockout mouse retinas, expression patterns of several molecular markers were examined by immunohistochemistry. Apoptotic cell death was detected by TUNEL method. Results: The analysis of LacZ expression pattern in heterozygote Tlx knock out mice has revealed that Tlx first begins to be expressed mainly at the innermost layer of embryonic retina. Accordingly, in the Tlx knockout mouse retina, the apoptotic cell death was first observed in the ganglion cell layer at around E17, and thereafter increased cell death proceeds in the inner nuclear layer. The general thinning of each retinal layers, especially the inner retina, was ceased by 1 month after birth. However, the overall expression patterns of several retinal specific markers were not changed from the wild type. ERG became nearly non-recordable at 1 month after birth. Most importantly, in addition to the retinal degeneration, we have found that the vascular formation and expression of proteins thought to be involved in the angiogenesis have been severely disturbed in the Tlx knockout retina. Conclusion: The above data strongly suggests that Tlx plays an important role for the development of neural retina and vascular formation during the course of retinal development. To investigate causative relationships between retinal degeneration and vascular malformation by the absence of Tlx, we are currently analyzing the possible downstream molecular events triggered by the expression of Tlx in the development of retinal structures.
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