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.

Postnatal Thyroid Hormone Supplementation Rescues Developmental Abnormalities Induced by Congenital-Neonatal Hypothyroidism in the Rat Retina

“…Peritomy was performed, the lens was carefully removed and the posterior eyecup was obtained and subsequently fi xed by soaking in 0. of the retroequatorial retina in the temporal superior quadrant (suitably oriented to show the transsectional surface of the middle zone between the peripheral and central retina) was immersed and slightly shaken in fi xative for an additional 200 min. The eye samples were then osmicated, dehydrated and embedded in Epon resin, as described elsewhere [31][32][33][34] . Serial semithin transverse sections of the retina were obtained using an LKB ultramicrotome and subsequently stained with toluidine blue for examination under an Olympus BX50 light microscope.…”

“…Previously, we have described the crucial role of TH in embryonic development of the head, face and eyeballs [31,32] and also for normal optic nerve and retina in the rat [33,34] . We now show that TH contribute to the postnatal development and maturation of the retina by directly depicting retinal architecture.…”

Photoreceptor Differentiation during Retinal Development, Growth, and Regeneration in a Metamorphic Vertebrate

“…The neural retina can be a target for metamorphic transformation Shand et al, 1999Shand et al, , 2002Helvik et al, 2001), and such metamorphic reorganization of the retina is likely to impact visual function, including color vision and absolute visual sensitivity. Furthermore, the metamorphic transition in vertebrates is driven by thyroid hormone (TH) signaling mechanisms (Inui and Miwa, 1985;Graf and Baker, 1990;Denver et al, 1997;Denver, 1998;Tata, 1999;Power et al, 2001), and because TH signaling has been implicated in retinal development (Browman and Hawryshyn, 1992;Kelley et al, 1995;Ng et al, 2001;Sevilla-Romero et al, 2002;Harpavat and Cepko, 2003;Cossette and Drysdale, 2004), the neural retina of metamorphic fish provides additional advantages for investigating the mechanisms that control cell differentiation in the developing, growing, and regenerating CNS.…”

Development of Contrast Sensitivity in Infants with Prenatal and Neonatal Thyroid Hormone Insufficiencies

“…In the retina, TH is needed (15)(16)(17) for the differentiation of cones versus rods (18,19), specific cone subtypes (20), and retinal oligodendrocyte precursor cells (21) and for the production of essential proteins (22,23). Animal models demonstrate that when TH is lacking at a particular time prenatally, visual development and functioning will be impaired (20).…”