Role of thyroid hormone in craniofacial and eye development using a rat model

Thyroid hormones (TH) are essential for somatic and neural development. Epi demiological studies have pointed to TH-dependent craniofacial features occ urring during development. In an attempt to elucidate the precise role of T H 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 H G animals were obtained at key developmental stages and processed for scann ing 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 mum(2); p < 0.05 ) and volume (3.96 +/- 0.141 vs. 8.09 +/- 0.123 mum(3); p < 0.05) were foun d in the HG with respect to the controls. In addition, a delayed prenatal e ye closure and postnatal eye opening took place in the treated rats. The ph otoreceptor 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 retarde d disc formation) and significantly lower values for ganglion cell nuclear volumes (p < 0.001) and nuclear pore density (p < 0.01) were observed in th e 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 l oss of TH actions involved in anterior-posterior development of the head an d face and the loss of TH-dependent signals crucial for cell differentiatio n, migration, proliferation and establishment of definitive cell phenotypes in the eyes may appear. Gestational and neonatal screenings for thyroid fu nctioning are suggested to paediatricians and ophthalmologists in order to prevent craniofacial malformations and visual abnormalities. Copyright (C) 2001 S. Karger AG, Basel.