Low Thyroid Hormone Levels Impair the Perinatal Development of the Rat Retina

Abstract

Eye development is regulated by multiple agents including hormones and growth factors. Thyroid hormone (triiodothyronine, or T₃, and the prohormone thyroxine, or T₄) plays a crucial role in the development of the central nervous system. Here we have examined the effects of low T₃/T₄ levels (hypothyroid status) on the developing rat retina during the perinatal stage. Eyes from control (CG) and T₃/T₄-deficient (HG) fetuses (E19 and E21) and newborn (P0, P3, P5 and P7) rats were obtained by administering a chemical antithyroid solution (0.02% methyl-mercaptoimidazole +1% ClOK₄) in the tap water to the dams and their offspring, from E9 and throughout gestation until they were killed. Perinatal eyes were processed for light and electron transmission microscopy and subjected to morphological and morphometric analyses. Low T₃/T₄ levels led to decreased retinal growth during the perinatal stage. In addition, the retinas from the HG presented fewer neuroblasts than those of their euthyroid counterparts (at E21: 705 ± 83 cells per constant area of 4 × 10⁴ µm² vs. 440 ± 60 cells per constant area of 4 × 10⁴ µm²; p = 0.010). During development the index of mitosis in the retina peaked at E21, falling at the end of the 1st postnatal week. Significantly lower values were observed in the HG (at P5: 0.803 ± 0.374 mitoses/cells % vs. 0.349 ± 0.180 mitoses/cells %; p = 0.004). Furthermore, we have found that low T₃/T₄ levels delayed and/or altered a series of developmental processes occurring in the retina during the perinatal stage such as layering and differentiation of several cell types. Our results demonstrate that thyroid hormone regulates rat neuroretinogenesis.