Tlx, an Orphan Nuclear Receptor, is Critical for the Control of Retinal Cell Numbers and Glial Development.

Abstract

Abstract: : Purpose: We previously reported that Tlx, an orphan nuclear receptor, knockout(KO)mouse showed the phenotype of retinal degeneration and impaired vasculogensis. In the present study, we investigated how and by which cell type Tlx plays roles in the control of retinal development and vasculogensis. Methods: We first identified the cells by which Tlx is expressed through the use of lacZ knock–in marker and retinal specific antibodies. The process of retinal degeneration of Tlx KO mouse was analyzed by light microscopy, electron microscopy and TUNEL method. The process of impaired vasculogenesis was also analyzed by immunohistochemistry. To examine if the retinal ischemia was involved in the retinal degeneration, explant culture of Tlx KO retina was conducted. Results:Tlx expression was initially located in the retinal progenitor cells and then confined to Müller glial cells during the postnatal stage. Tlx was also expressed transiently by retinal astrocytes migrating over the inner surface of retina. The lack of Tlx led to the defect in the regulation of cell numbers at each nuclear layer and hypoplasia of Müller cells. The delayed migration and impaired network formation of astrocyte over the retina was observed in Tlx KO retina, which preceded the lack of vasculogenesis. Conclusions: Tlx appears to regulate the proper numbers of distinct neuronal subtypes at each nuclear layer and is required for the development of Müller cells and astrocytes. The regulation of the retina–intrinsic and –extrinsic developmental programs by Tlx is critical for the proper retinal organization.

Keywords: astroglia: optic nerve head • retinal degenerations: cell biology • Muller cells