Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function

Houbrechts, Anne; Vergauwen, Lucia; Bagci, Enise; houcke, Jolien Van; Heijlen, Marjolein; Kulemeka, Bernard; Hyde, David R.; Knapen, Dries; Darras, Veerle

doi:10.1016/j.mce.2016.01.018

Cited by 55 publications

(62 citation statements)

References 57 publications

(71 reference statements)

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“…Similar results have been observed using a zebrafish model in which morpholino-mediated transient knockdown of all three deiodinases promoted photoreceptor loss (Houbrechts et al, 2016). Reduction in levels of thyroid hormone also has a protective effect on cone survival in animal models of retinal degeneration (Ma et al, 2014).…”

Section: Discussionsupporting

confidence: 85%

The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

et al. 2017

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SUMMARY Circadian clocks regulate various aspects of photoreceptor physiology, but their contribution to photoreceptor development and function is unclear. Cone photoreceptors are critical for color vision. Here, we define the molecular function of circadian activity within cone photoreceptors and reveal a role for the clock genes Bmal1 and Per2 in regulating cone spectral identity. ChIP analysis revealed that BMAL1 binds to the promoter region of the thyroid hormone-activating enzyme type 2 iodothyronine deiodinase (Dio2) and thus regulates the expression of Dio2. Thyroid hormone treatment resulted in a partial rescue of the phenotype caused by the loss of Bmal1, thus revealing a functional relationship between Bmal1 and Dio2 in establishing cone photoreceptor identity. Furthermore, Bmal1 and Dio2 are required to maintain cone photoreceptor functional integrity. Overall, our results suggest a mechanism by which circadian proteins can locally regulate the availability of thyroid hormone and influence tissue development and function.

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Section: Discussionsupporting

confidence: 85%

The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

et al. 2017

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“…It is possible that a gradient in T 3 or its receptors, as reported for the mouse retina, may be responsible for the spatio‐temporal pattern of corner cone loss in salmonid fishes. In the zebrafish and mouse, deiodinase knockdown reduces the density of retinal photoreceptors. In the present study, T 3 levels in the retina were not measured, although the similarity in cone densities suggest that T 3 dynamics were similar between fish groups, if T 3 indeed induces corner cone loss.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Many vertebrates express multiple opsins within a photoreceptor [7][8][9][10][11] and some can modulate the primary opsin expressed within individual photoreceptor types during development. 7,9,[12][13][14][15][16][17][18][19] In rodents, 13,20,21 human organoids 22 and fishes, [23][24][25][26] this regulation involves the action of thyroid hormone (3,5,3′-triiodothyronine, T 3 , or l-thyroxine, T 4 ) binding to thyroid hormone receptors (TRβs or, potentially, TRαs 24 ), with T 3 itself being locally regulated in the retina of some species through the action of deiodinase enzymes. 22,26,27 In salmonid fishes, treatment of the holding water with T 4 induces an opsin switch from SWS1 to SWS2 in the single cone photoreceptors, transforming them from UV to short wavelength sensitive (S) cones.…”

mentioning

confidence: 99%

Growth hormone regulates opsin expression in the retina of a salmonid fish

Flamarique

Ahmed

Cheng

et al. 2019

J Neuroendocrinology

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Colour vision relies on retinal photoreceptors that express a different predominant visual pigment protein (opsin). In several vertebrates, the primary opsin expressed by a photoreceptor can change throughout ontogeny, although the molecular factors that influence such regulation are poorly understood. One of these factors is thyroid hormone which, together with its receptors, modulates opsin expression in the retinas of multiple vertebrates including rodents and salmonid fishes. In the latter, thyroid hormone induces a switch in opsin expression from SWS1 (ultraviolet light sensitive) to SWS2 (short wavelength or blue light sensitive) in the single cone photoreceptors of the retina. The actions of other hormones on opsin expression have not been investigated. In the present study, we used a transgenic strain of coho salmon (Oncorhynchus kitsutch) with enhanced levels of circulating growth hormone compared to that of wild siblings to assess the effects of this hormone on the SWS1 to SWS2 opsin switch. Transgenic fish showed a developmentally accelerated opsin switch compared to size‐matched controls as assessed by immunohistological and in situ hybridisation labelling of photoreceptors and by quantification of transcripts using quantitative polymerase chain reaction. This accelerated switch led to a different spectral sensitivity maximum, under a middle to long wavelength adapting background, from ultraviolet (λmax ~ 380 nm) in controls to short wavelengths (λmax ~ 430 nm) in transgenics, demonstrating altered colour vision. The effects of growth hormone over‐expression were independent of circulating levels of thyroid hormone (triiodothyronine), the hormone typically associated with opsin switches in vertebrates.

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“…B) Increased Gpx4 protein level in in Dio2 2/2 , but not Dio2 +/2 , mice (data not shown). Moreover, knockdown of Dio2 has been shown to affect zebrafish eye development at the level of gene expression, morphology, and function (62). For those reasons, we used retinas of Rpe65 2/2 /Nrl 2/2 /Dio2 +/2 mice in our biochemical evaluations.…”

Section: Dio2 Deficiency Improves Cone Survival and Function In Rpe65mentioning

confidence: 99%

Deficiency of type 2 iodo‐ thyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice

Yang

Butler

et al. 2018

FASEB j.

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Thyroid hormone (TH) signaling has been shown to regulate cone photoreceptor viability. Suppression of TH signaling with antithyroid drug treatment or by targeting iodothyronine deiodinases and TH receptors preserves cones in mouse models of retinal degeneration, including the Leber congenital amaurosis Rpe65-deficient mice. This work investigates the cellular mechanisms underlying how suppressing TH signaling preserves cones in Rpe65-deficient mice, using mice deficient in type 2 iodothyronine deiodinase (Dio2), the enzyme that converts the prohormone thyroxine to the active hormone triiodothyronine (T3). Deficiency of Dio2 improved cone survival and function in Rpe65 and Rpe65-deficiency on a cone dominant background ( Rpe65/ Nrl) mice. Analysis of cell death pathways revealed that receptor-interacting serine/threonine-protein kinase (RIPK)/necroptosis activity was increased in Rpe65/ Nrl retinas, and Dio2 deficiency reversed the alterations. Cell-stress analysis showed that the cellular oxidative stress responses were increased in Rpe65/ Nrl retinas, and Dio2 deficiency abolished the elevations. Similarly, antithyroid drug treatment resulted in reduced RIPK/necroptosis activity and oxidative stress responses in Rpe65/ Nrl retinas. Moreover, treatment with T3 significantly induced RIPK/necroptosis activity and oxidative stress responses in the retina. This work shows that suppression of TH signaling reduces cellular RIPK/necroptosis activity and oxidative stress responses in degenerating retinas, suggesting a mechanism underlying the observed cone preservation.-Yang, F., Ma, H., Butler, M. R., Ding, X.-Q. Deficiency of type 2 iodothyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice.

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Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function

Cited by 55 publications

References 57 publications

The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function

Growth hormone regulates opsin expression in the retina of a salmonid fish

Deficiency of type 2 iodo‐ thyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice

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