Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats

Abstract

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction.

Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with in Vitro Testing and Adverse Outcome Pathway Approaches

“…The observations in humans are supported by rodent studies where neurodevelopmental impairments result from moderate and transient reductions in serum TH induced by chemical exposures (Ausó et al. 2004; Boyes et al. 2018; Gilbert 2011; Gilbert et al.…”

Biphasic expression of thyroid hormone receptor TRβ1 in mammalian retina and anterior ocular tissues

“…This may suggest a role for thyroid hormone in visual processing in the inner retina but this remains to be explored. It has been reported that hypothyroidism impairs visual-evoked potentials in central pathways in rats ( 13 , 61 ).…”

“…Thyroid hormone also influences photoreceptor differentiation and survival. Hypothyroidism in rodents impairs M opsin expression ( 10 – 12 ) and responses to green wavelength light ( 13 ). Hyperthyroidism can alter opsin expression ( 14 ) but excesses cause cone cell death in mice ( 15 , 16 ).…”

Thyroid Disease Is Associated with Higher Age-Related Macular Degeneration Risk: Results from a Meta-Analysis of Epidemiologic Studies

“…Population studies have revealed that high serum thyrotropin levels are associated with retinal arteriolar narrowing [8]. Animal studies have demonstrated that moderate levels of pre- and postnatal TH insufficiency lead to alterations in visual function in adult rats [9]. These findings highlight the important role of TH in regulating various visual functions.…”