Thyroid Hormone and Retinal Development: An Emerging Field

Harpavat, Sanjiv; Cepko, Constance L.

doi:10.1089/105072503770867183

Cited by 54 publications

(41 citation statements)

References 53 publications

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“…This is consistent with the function of TH as a signaling mechanism in vertebrate metamorphosis (Power et al, 2001), and in retinal development and opsin expression (Allison et al, 2003;Browman and Hawryshyn, 1992;Harpavat and Cepko, 2003;Roberts et al, 2006). Current efforts in our laboratory are aimed at determining the spatiotemporal expression patterns of RH2A and B opsins in coho and other Pacific salmonids.…”

Section: Two Rh2 Opsin Subtypes In Coho Mws Conessupporting

confidence: 68%

Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch)

Temple

Ramsden

Haimberger

et al. 2008

Journal of Experimental Biology

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SUMMARYThe role of exogenous thyroid hormone on visual pigment content of rod and cone photoreceptors was investigated in coho salmon (Oncorhynchus kisutch). Coho vary the ratio of vitamin A 1 -and A 2 -based visual pigments in their eyes. This variability potentially alters spectral sensitivity and thermal stability of the visual pigments. We tested whether the direction of shift in the vitamin A 1 /A 2 ratio, resulting from application of exogenous thyroid hormone, varied in fish of different ages and held under different environmental conditions. Changes in the vitamin A 1 /A 2 visual pigment ratio were estimated by measuring the change in maximum absorbance (λ max ) of rods using microspectrophotometry (MSP). Exogenous thyroid hormone resulted in a longwavelength shift in rod, middle-wavelength-sensitive (MWS) and long-wavelength-sensitive (LWS) cone photoreceptors. Rod and LWS cone λ max values increased, consistent with an increase in vitamin A 2 . MWS cone λ max values increased more than predicted for a change in the vitamin A 1 /A 2 ratio. To account for this shift, we tested for the expression of multiple RH2 opsin subtypes. We isolated and sequenced a novel RH2 opsin subtype, which had 48 amino acid differences from the previously sequenced coho RH2 opsin. A substitution of glutamate for glutamine at position 122 could partially account for the greater than predicted shift in MWS cone λ max values. Our findings fit the hypothesis that a variable vitamin A 1 /A 2 ratio provides seasonality in spectral tuning and/or improved thermal stability of visual pigments in the face of seasonal environmental changes, and that multiple RH2 opsin subtypes can provide flexibility in spectral tuning associated with migration-metamorphic events.

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Section: Two Rh2 Opsin Subtypes In Coho Mws Conessupporting

confidence: 68%

Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch)

Temple

Ramsden

Haimberger

et al. 2008

Journal of Experimental Biology

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“…Its involvement in mediating the visual changes that occur during amphibian metamorphosis have long been known (Hoskins, 1990), and it was also shown to influence chick and rat retinal progenitor development. Harpavat and Cepko reviewed the role of TH in retinal development in 2003 (Harpavat and Cepko, 2003). TH is distributed uniformly across the retina at birth, but during the period of M-cone differentiation between P4 and P10 forms a gradient with higher concentrations in the dorsal than ventral retina [ (Roberts et al, 2006); Figure 2B].…”

Section: Factors That Influence M-cone Differentiationmentioning

confidence: 99%

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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Rod and cone photoreceptors in the mammalian retina are special types of neurons that are responsible for phototransduction, the first step of vision. Development and maintenance of photoreceptors require precisely regulated gene expression. This regulation is mediated by a network of photoreceptor transcription factors centered on Crx, an Otx-like homeodomain transcription factor. The cell type (subtype) specificity of this network is governed by factors that are preferentially expressed by rods or cones or both, including the rod-determining factors neural retina leucine zipper protein (Nrl) and the orphan nuclear receptor Nr2e3; and cone-determining factors, mostly nuclear receptor family members. The best-documented of these include thyroid hormone receptor β2 (Trβ2), retinoid related orphan receptor Rorβ, and retinoid X receptor Rxrγ. The appropriate function of this network also depends on general transcription factors and co-factors that are ubiquitously expressed, such as the Sp zinc finger transcription factors and STAGA coactivator complexes. These cell type-specific and general transcription regulators form complex interactomes; mutations that interfere with any of the interactions can cause photoreceptor development defects or degeneration. In this manuscript, we review recent progress on the roles of various photoreceptor transcription factors and interactions in photoreceptor subtype development. We also provide evidence of auto-, para-, and feedback regulation among these factors at the transcriptional level. These protein-protein and protein-promoter interactions provide precision and specificity in controlling photoreceptor subtype-specific gene expression, development and survival. Understanding these interactions may provide insights to more effective therapeutic interventions for photoreceptor diseases.

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“…In mammals, TH is critical for proper development of the central nervous system, including the retina (Bernal et al, 2003;Ng et al, 2001;Harpavat and Cepko, 2003). The TH receptors (TR), TRa and TRb, have both been detected in the retina of mice, chicken, the African clawed frog (Xenopus laevis) and winter flounder (Pleuornectes americanus), and have been shown to be involved in opsin expression and cone development (Sjöberg et al, 1992;Cossette and Drysdale, 2004;Mader and Cameron, 2006;Nunez.…”

Section: Introductionmentioning

confidence: 99%

Systemic thyroid hormone is necessary and sufficient to induce ultraviolet-sensitive cone loss in the juvenile rainbow trout retina

Raine

Coffin

Hawryshyn

2010

Journal of Experimental Biology

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SUMMARYRainbow trout possess ultraviolet-sensitive (UVS) cones in their retina that degenerate naturally during development. This phenomenon can be induced with exogenous thyroxine [T4, a thyroid hormone (TH)] treatment. However, the previous T4 exposure experiments employed static water immersion; a method that could introduce confounding stress effects on the fish. Because of this, it was uncertain if T4 alone was sufficient to induce retinal changes or if stress-related hormones were also necessary to initiate this process. Furthermore, it was unclear whether endogenous T4 was the factor responsible for initiating natural UVS cone loss during development. The current study examined the role of systemic T4 on the juvenile rainbow trout retina using a slow-release implant. Exogenous T4 treatment resulted in SWS1 opsin downregulation and UVS cone loss after four weeks of exposure, signifying that T4 is sufficient to induce this process. Blocking endogenous T4 production with propylthiouracil (PTU, an anti-thyroid agent) attenuated SWS1 downregulation and UVS cone loss in the retina of naturally developing rainbow trout, suggesting that endogenous T4 is necessary to initiate retinal remodelling during development. Quantitative real-time RT-PCR analysis demonstrated that several TH-regulating components are expressed in the trout retina, and that expression levels of the TH receptor isoform TRb and the type 2 deiodinase (D2) change with T4 treatment. This suggests that T4 may act directly on the retina to induce UVS cone loss. Taken together, these results demonstrate that systemic TH is necessary and sufficient to induce SWS1 opsin downregulation and UVS cone loss in the retina of juvenile rainbow trout.

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Thyroid Hormone and Retinal Development: An Emerging Field

Cited by 54 publications

References 53 publications

Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch)

Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch)

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

Systemic thyroid hormone is necessary and sufficient to induce ultraviolet-sensitive cone loss in the juvenile rainbow trout retina

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