Thyroid hormones (TH) are essential for somatic and neural development. Epidemiological studies have pointed to TH-dependent craniofacial features occurring during development. In an attempt to elucidate the precise role of TH in the developing eyes and adnexa (orbit, lids, nasolacrimal structures), we analysed the craniofacial and eyeball developmental characteristics in a rat model of congenital-neonatal hypothyroidism (HG), induced by combined chemical-surgical thyroidectomy. The heads and eyeballs from control and HG animals were obtained at key developmental stages and processed for scanning electron, light and transmission electron microscopy. On embryological day 13 (E13), significantly reduced values for head parameters (25% less), optic primordia area (0.053 ± 0.0085 vs. 0.111 ± 0.012 µm²; p < 0.05) and volume (3.96 ± 0.141 vs. 8.09 ± 0.123 µm³; p < 0.05) were found in the HG with respect to the controls. In addition, a delayed prenatal eye closure and postnatal eye opening took place in the treated rats. The photoreceptor and ganglion cell layer thickness displayed significantly lower values (p < 0.001) in HG, at each developmental time point. Postnatally, a delay in photoreceptor outer segment morphogenesis (in relation to retarded disc formation) and significantly lower values for ganglion cell nuclear volumes (p < 0.001) and nuclear pore density (p < 0.01) were observed in the TH-deficient animals. All data suggest that TH play a pivotal role in the development of the face and eye. Therefore, a series of defects due to a loss of TH actions involved in anterior-posterior development of the head and face and the loss of TH-dependent signals crucial for cell differentiation, migration, proliferation and establishment of definitive cell phenotypes in the eyes may appear. Gestational and neonatal screenings for thyroid functioning are suggested to paediatricians and ophthalmologists in order to prevent craniofacial malformations and visual abnormalities.

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.

Thyroid hormones (TH) play a key role in central nervous system development. We have studied the influence of congenital and neonatal hypothyroidism on retinal development and the effects of postnatal TH supplementation. An experimental model was set up using Wistar rats by inducing chemical thyroidectomy during gestation and suckling. Eyes from control (CG) and TH-depleted (THDG) groups of animals were obtained at postnatal days 10 and 25. In the THDG, there was a significant reduction in the retinal thickness and layering, retinal volume, cell number and nuclear volumes in all layers. A third group of rats, made hypothyroid during the gestational and neonatal period and then supplemented with TH (THSG), showed a recovery of both the retinal thickness [at P25: 188.5 ± 9.2 µm (THSG) vs. 175.8 ± 16.1 µm (THDG), p < 0.001, and 210.8 ± 8.9 (CG)] and total retinal cell number [at P25: 6.9 × 10⁶ (THSG) vs. 3.7 × 10⁶ (THDG) cells, p < 0.001, and 5.3 × 10⁶ cells (CG)]. Light and electron microscopy studies confirmed that TH deprivation altered the organization of the retina, which was mostly normalized by hormone administration. Our data show that TH regulates intrinsic mechanisms for controlling retinal cytoarchitecture and layering, and that alterations in retinal maturation induced by congenital-neonatal TH deficiency can be at least partially rescued by early hormonal treatment in vivo.