AUTHOR=Ng Lily , Liu Hong , Liu Ye , Forrest Douglas TITLE=Biphasic expression of thyroid hormone receptor TRĪ²1 in mammalian retina and anterior ocular tissues JOURNAL=Frontiers in Endocrinology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1174600 DOI=10.3389/fendo.2023.1174600 ISSN=1664-2392 ABSTRACT=The retina is increasingly recognized as a target of thyroid hormone. We previously reported critical functions for thyroid hormone receptor TRb2, encoded by Thrb, in cones, the photoreceptors that mediate color vision. TRb1, another Thrb receptor isoform, is widely expressed in other tissues but little studied in the retina. Here, we investigate these N-terminal isoforms by RNA-sequencing analysis and reveal a striking biphasic expression profile for TRb1 in mouse and human retina. In contrast to the early TRb2 peaks, TRb1 peaks later during retinal maturation or during later differentiation in human retinal organoids. This switch in receptor profiles was confirmed in tissue development using lacZ reporter mice. Furthermore, TRb1 localized in cones, amacrine cells and ganglion cells in contrast to the restricted expression of TRb2 in cones. Intriguingly, TRb1 was also detected in the retinal pigmented epithelium and in anterior structures in the ciliary margin zone, ciliary body and iris, suggesting novel functions in non-retinal eye tissues. Although TRb1 was detected in cones, TRb1-knockout mice displayed only minor changes in opsin photopigment expression and normal electroretinogram responses. Our results suggest that strikingly different temporal and cell-specific controls over TRb1 and TRb2 expression may underlie thyroid hormone actions in a range of ocular cell types. The TRb1 expression pattern suggests novel functions for thyroid hormone in retinal and non-neural ocular tissues.