Effects of Low-Dose Embryonic Thyroid Disruption and Rearing Temperature on the Development of the Eye and Retina in Zebrafish

摘要

Thyroid hormones are required for vertebrate development, and disruption of the thyroid system in developing embryos can result in a large range of morphologic and physiologic changes, including in the eye and retina. In this study, our anatomic analyses following low-dose, chronic thyroid inhibition reveal that both methimazole (MMI) exposure and rearing temperature affect eye development in a time- and temperature-dependent fashion. Maximal sensitivity to MMI for external eye development occurred at 65 hr postfertilization (hpf) for zebrafish reared at 28 degrees C, and at 69 hpf for those reared at 31 degrees C. Changes in eye diameter corresponded to changes in thickness of two inner retinal layers: the ganglion cell layer and the inner plexiform layer, with irreversible MMI-induced decreases in layer thickness observed in larvae treated with MMI until 66 hpf at 28 degrees C. We infer that maximal sensitivity to MMI between 65 and 66 hpf at 28 degrees C indicates a critical period of thyroid-dependent eye and retinal development. Furthermore, our results support previous work that shows spontaneous escape from MMI-induced effects potentially due to embryonic compensatory actions, as our data show that embryos treated beyond the critical period generally resemble controls