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.
Epidemiological and experimental studies suggest the involvement of lipid peroxidation (LPO) in retinal diseases. Clinicians usually prescribe antioxidants to help in the treatment of proliferative diabetic vitreoretinopathy and age-related macular degeneration. In spite of this, these processes inexorably induce visual impairment and may progress towards blindness. In addition to other pathogenic mechanisms not fully understood, it may be that peroxidic aldehydes from LPO occurring in the eyes, acting as cytotoxic chemicals, mediate in these chronic disorders. To test the mechanisms of removing peroxidic aldehydes from retinal cells and in an attempt to understand long-lasting changes induced by LPO, the distribution and activity of aldehyde dehydrogenases (ALDH) in the rat retina were studied and compared with the LPO sites induced by iron/nicotine adenine dinucleotide phosphate. Histochemical and immunocytochemical assays revealed the colocalization of LPO and ALDH, mainly in the photoreceptors and inner retinal layers. This suggests the involvement of ALDH in detoxifying peroxidic aldehydes from the retina. Any change in ALDH retinal expression and distribution might be of crucial importance in assessing the paths of LPO-mediated vitreoretinopathies. Further research is needed to evaluate these findings and their application to new ophthalmic therapy.
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