Endocrine regulation of multichromatic color vision

[helvella]

Don't try to get me to explain this! Just reporting the direct impact of thyroid hormone on colour vision is an important step.

There have been some posts here which mentioned shifts in colour perception. What has, perhaps, not been clear is where the shift happens. This paper appears to indicate it occurs in the cones of the retina - though additional effects might occur in the parts of the brain that process vision.

(The actual experimentation was done on zebrafish, not humans.)

Endocrine regulation of multichromatic color vision

Robert D. Mackin, Ruth A. Frey, Carmina Gutierrez, Ashley A. Farre, Shoji Kawamura, Diana M. Mitchell, and Deborah L. Stenkamp

PNAS first published August 5, 2019 doi.org/10.1073/pnas.190478...

1. Edited by Robert Johnston, The Johns Hopkins University, Baltimore, MD, and accepted by Editorial Board Member Jeremy Nathans July 8, 2019 (received for review March 25, 2019)

Significance

Primate and fish genomes contain tandemly replicated cone opsin genes. The human long wavelength-sensitive/medium wavelength-sensitive (LWS/MWS) tandem array underlies trichromatic color vision; mutations in this array cause altered color vision and retinal degenerations. Differential expression of human LWS vs. MWS is considered a stochastic event, whereby upstream enhancers associate with the promoter of the proximal or distal gene. We demonstrate that the endocrine signal thyroid hormone (TH) is a potent endogenous regulator of the orthologous zebrafish lws1/lws2 array, and of the tandemly quadruplicated rh2-1/rh2-2/rh2-3/rh2-4 array. TH promotes shifts in spectral sensitivity to longer wavelengths by changing expression of opsins in each array, indicating TH-coordinated control of visual function during organismal growth.

Abstract

Vertebrate color vision requires spectrally selective opsin-based pigments, expressed in distinct cone photoreceptor populations. In primates and in fish, spectrally divergent opsin genes may reside in head-to-tail tandem arrays. Mechanisms underlying differential expression from such arrays have not been fully elucidated. Regulation of human red (LWS) vs. green (MWS) opsins is considered a stochastic event, whereby upstream enhancers associate randomly with promoters of the proximal or distal gene, and one of these associations becomes permanent. We demonstrate that, distinct from this stochastic model, the endocrine signal thyroid hormone (TH) regulates differential expression of the orthologous zebrafish lws1/lws2 array, and of the tandemly quadruplicated rh2-1/rh2-2/rh2-3/rh2-4 array. TH treatment caused dramatic, dose-dependent increases in abundance of lws1, the proximal member of the lws array, and reduced lws2. Fluorescent lws reporters permitted direct visualization of individual cones switching expression from lws2 to lws1. Athyroidism increased lws2 and reduced lws1, except within a small ventral domain of lws1 that was likely sustained by retinoic acid signaling. Changes in lws abundance and distribution in athyroid zebrafish were rescued by TH, demonstrating plasticity of cone phenotype in response to this signal. TH manipulations also regulated the rh2 array, with athyroidism reducing abundance of distal members. Interestingly, the opsins encoded by the proximal lws gene and distal rh2 genes are sensitive to longer wavelengths than other members of their respective arrays; therefore, endogenous TH acts upon each opsin array to shift overall spectral sensitivity toward longer wavelengths, underlying coordinated changes in visual system function during development and growth.

Rest of full paper, including PDF option, available here:

pnas.org/content/early/2019...

[FarmerDJ]

Interesting article. Wondering if anyone on this forum has experienced any changes in their colour perception since having thyroid issues. I haven't personally but would be good to see if this result could possibly translate to being a human problem too.

[TSH110 in reply to FarmerDJ]

Mine was greatly affected. It was as if it was twilight all the time, a rather telling descriptor given the state I was in. I was very overtly hypothyroid by the time I was treated with my thyroid becoming non functional on initiation of Levothyroxine. My night vision was very poor and I had all sorts of visual disturbance, like double vision and dreadful starbursts around all lights at night but these may have been due to other aspects of the hypothyroidism which also included short but intense bouts of hyperthyroidism. One eye was more affected than the other as well I had a huge diffence in pupil size which might have had some significance. I think it has retired to normal now thank goodness! I take NDT.

[Hidden in reply to TSH110]

Tsh110, I have gone from pretty severe overmedication to now undermedicated and for the last several months I have had increasingly worse night vision where I have Starbursts and don't see well in a dimly lit room. I'm in the US and had a doctor tell me that the thyroid controls photoreceptors but not many Studies have been done on it. I want to ask you how long it took for your vision to get back to normal once you started treating your hypothyroidism?

[TSH110 in reply to Hidden]

It is improved but not as good as it once was. It took about three years to improve but I think it could have started as soon as I took medication. I was on Levo fir two years but never felt right. I now take NDT which suits me much better. I still have some star burst at night with lights and I struggle to read if I don’t get string illumination my glasses are better in this respect than contacts. I am glad I don’t drive it would be awful at night. I hope yours starts to improve. I also went very deaf and have had an excellent recovery there I hear much better tho it is not superb it is not deafness any more.

[TSH110]

Very interesting - my colour vision was badly affected. Colours lost all their vibrancy everything seemed dull. My night vision was dreadful. I had heard vision tending more towards black and white can occur with hypothyroidism and it was something to do with the cones. It would make sense that the brain side of things might also be affected, but I’m afraid despite knowing quite a bit about how the eyes work, the extract is not very illuminating to me - pity you can’t explain it or perhaps you can but it would take an eternity! Maybe the light sensitive chemicals allowing for colour vision are not replenished quickly enough in the retina (I may have this all wrong). T3 will be key.

[helvella Administrator Thyroid UK in reply to TSH110]

For myself, it just felt as if the chrominance had been turned down a touch (for those who remember colour televisions of a certain vintage!).

And, yes, night vision was worse, as was coping with oncoming headlamps.

But I have to emphasise that my experience might have gone without being really obvious had I not already got some knowledge hence heightened awareness.

[silverfox7]

Interesting! I did have a stage where everything (suddenly) became more vibrant. It wasn't as though I was sitting there one day and a light switched on but more a feeling when I got up that it was a sunny day but actually wasn't. I seem to remember at the time I had recently had a medication change but when and what I've no idea but could well have been when changed back to NDT. Will look if I documented it anywhere and if so will report back but it was an obvious brightening. Has it stayed or have I got used to it-can't say as that could be a very fine line but I can't ever remember that I associated it with a change of glasses so the world was now in focus. I do remember that the yellow was more prominent but whether that says something again I don't know.

[asiatic]

I was diagnosed TED 4 years ago now in recovery but still with double vision. I find my colour vision greatly affected and colour appears different depending which eye I use. E.g. the background on my kindle is blue grey with one eye and pink grey with other. Mid way through my treatment the orthoptist changed the test book for colour vision. The new one involves looking at sets of 3 dots and you have to say if they are all the same. I find it impossible as the dots keep changing colour . I have noticed on the British Thyroid Assosc. Site someone in London is doing research into colour vision and TED and is looking for volunteers.

[TSH110 in reply to asiatic]

That is really interesting. I was never diagnosed with TED only autoimmune thyroiditis but therexwas a considerable difference in colour perception between my eyes not different colours as such but a difference in colour vibrancy. I put it down to the very obvious discrepancy in pupil size. it was never commented on at the opticians but I can’t inagine it was normal. Not sure if they are still like that, but the. Colour perception between eyes appears virtually identical now. I had short periods of hyperthyroidism between longer bout of hypothyroidism. I was very overt before treatment began. It was only when I took NDT that my symptoms pretty much resolved.

[Hidden]

Very interesting. I think it means that Thyroid hormones change the sensitivity of the cone cells to different wavelengths, by affecting the expression of certain genes. Is that correct?

I haven't been aware of problems with colour vision but did have a phase of sometimes getting slight double vision.. I thought it meant I needed new glasses, or my cataracts were getting worse.

It reminds me of a TV programme years ago about a man who used to try out different toadstools (cautiously!) to see if they were edible. He said he tried one and everything seemed to turn BLUE! Needless to say, that particular experiment was abandoned!

[helvella Administrator Thyroid UK in reply to Hidden]

The more I have learned about mushrooms, the less likely I am to eat any - even those "known" to be safe!

One which is famously good for eating has recently had its safety questioned - Chicken of the woods. It doesn't help that there can be differences between say, the precise fungus in the USA and in Europe despite seeming identical. Nor that some which seem fairly safe build-up over long periods.

[TSH110 in reply to helvella]

All the supposed edible ones you can collect yourself but. It buy make me feel decidedly queasy - bluwits, shaggy inkcaps for example - perhaps they are not commonly eaten because they do not agree with everyone?

[TSH110 in reply to Hidden]

What a nutter!

[Hidden]

I know this post is a few months old but I am having starburst vision at night also what they called ghosting around reflective type images. Left eye much worse than right but right is getting worse. I'm in the US and have actually had a couple doctors say the thyroid controls your photoreceptors so therefore affects vision. I was very overmedicated for many months and now with reduction in medicine have gone very hypo and I'm experiencing hypo symptoms including this night vision problem. I am very relieved to hear others have struggled with this type of problem. Any comments on how long it takes for the vision to improve once treatment starts?

[helvella Administrator Thyroid UK in reply to Hidden]

For me, and my very minor experience, I'd say it was between the spring when we no longer needed headlamps most of the time to the next autumn. By then I was much, much better.

Trouble with thyroid is that we are all different and everything is slow.

[Hidden in reply to helvella]

Thank you hellvela- so appreciate connecting w someone who has had similar visual disturbances.