13 replies to this topic

[Cassox]

Hi. I'm working involved in a research project attempting to augment vision with 3,4-dehydroretinol. This was accomplished via the US military prior to the 30's, but since largely forgotten. The outcome of the research isn't available, apparently even through FOIA channels. So were doing our own project whereby we maintain a Vit. A defincient diet and then supplementing with 3,4-dehydroretinol: vitamin A2. A2 is a similar compound to A1 which is found in the eyes of freshwater fish. As retinal cells uptake the A2, the visual spectrum to which the eye is sensitive is shifted in the IR region.

We are doing this: https://www.microryz...e-near-infrared

You can also get more information here: http://www.blogger.c...=8;src=postname

Ok, so I'm not just posting this to advertise the project; I figured that there are of people here very interested in molecular biology that could suggest ways to circumvent the need for dietary restriction. Retinol is stored in the liver and release is controlled homeostatically. There is an enzyme that allows it to be converted into Retinal, which is the form the photosensitive cells of the eye need: Retinol Dehydrogenase. Is there any way this pathway could be blocked?

[Nattzor]

The blogger account is not open for the public.

[gwern]

Cassox, could you elaborate on the FOIA you tried? I was thinking of doing a FOIA request for a dual n-back thing, and would be interested to hear more about the process.

[Cassox]

Oh, sorry! It's a bad link. Here: http://augmentationl...-3-dehydro.html

Also, Re: FOIA requests, there are two great sites here that will explain the process.

http://www.fcc.gov/g...le-foia-request

http://www.foia.gov/

It's primarily a send of request and wait to be denied kind of a process. I may still get a response or two. We'll see.

[Nattzor]

I assume you'll control the diet weeks earlier, getting less and less vit A?

"If the retina could be encouraged to use some alternative form of vitamin A in its manufacture of photopigments, the spectral sensitivity of those photopigments would be abnormal, perhaps extending into infrared radiation" - I assume this means you wont get any results with 3 days worth of A2, but rather the effects will build up during a period of time.

[Darryl]

I'm sorry I can't help, but as I've spent time playing with Wratten 87 filters over camera flashes and 850nm LED lighting, I will note humans naturally have faint sensitivity to IR even out past 800 nm.

For those curious about color vision, this summary of the evolutionary kludges involved in primate color vision may be of interest. Perhaps someday some transgenic humans will have the amazingly well-resolved color vision of birds.

[Cassox]

Actually, we plan for a diet completely deficient in Vit. A for a period of nearly 6 months. Turnover of Opsins are actually rather rapid; as little as ten days once the A2 can outcompete the Vit. A. We are fortunate in that we are being endorsed by the CEO of Soylent. He's making us a batch of Soylent without Vitamin A.

[ElysiumFields]

There are definitely ways to block enzymes of the retinol dehydrogenase class, although there's much more info on blocking retinal dehydrogenase or blocking this pathway via means that probably aren't available/relevant to you like gene knockout or disruption. Still there are ways to inhibit activity of retinol dehydrogenases, as just one example if you look up "potent inhibitors of 9-cis retinol dehydrogenase" you'll see a patent on google patents, I think the problem is that retinol dehydrogenase is just a name for any enzyme that catalyzes the reaction | Retinol + NAD⁺ retinal + NADH + H⁺ | so its going to be pretty hard to find a substance that inhibits them all. A lot of things seem to pop up that "inhibit oxidation/conversion of retinol to retinolic acid" and these may or may not be useful because it either means they inhibit conversion by blocking retinol dehydrogenases, or it could mean they ultimately block retinal dehydrogenases. Your best bet is to identify which retinol dehydrogenases are the most important to inhibit in your case and then ask about those. The other best method of research besides targeting certain enzymes will probably just be to look into things that inhibit retinol oxidation, without looking for things that focus directly on their activity on the enzymes. Actually when I think about there's a paper "Retinoic Acid Regulates Retinol Metabolism via Feedback Inhibition of Retinol Oxidation and Stimulation of Retinol Esterification in Ferret Liver", which probably transfers over to humans since one of the main purposes of converting retinol to retinal in the first place is because this is the rate limiting step in the synthesis of retinoic acid, so if your body already has retinoic acid it may signal to the body that it doesn't need to convert retinol to retinal anymore. Retinoic acid is extremely important in your body anyway and the lack of it would be one of the main dangers of inhibiting retinol dehydrogenase, so I think although people normally don't supplement retinoic acid because of risks (mainly the risk hypervitaminosis A which you should be wary of since its mainly caused by excess retinoid intake, but if you're already on the vitamin A deprived diet and you have the right level of retinoic acid intake then I don't think this will be a danger) anyway despite it not normally being used as a supplement I think in your case it would be one of the best things to do since retinoic acid is actually the main active form of vitamin A (besides in terms of pigment and a few metabolic processes) it will alleviate a lot of the affects of retinal deprivation and will further help with lowering of retinol dehydrogenase.The best method of research for stopping conversion of retinol to retinal will probably .The Lutein in soylent may increase retinol dehydrogenase if you're not using retinoic acid because all though it's not a provitamin for retinal it will activate retinoic acid receptors, which could make the body try to produce more retinoic acid. Also with regards to the soylent (you may already know this but just in case) you should also make sure the batch of lycopene usually contained soylent- lycopene can be converted to beta-carotene which can then be converted to retinal by the enzyme Beta-carotene 15,15'-dioxygenase, I don't think the Alpha-carotene is an issue but you should probably verify that yourself. By the way here two other things that might be of interest for you: Zinc will have a mixed effect on your results- higher zinc is correlated with higher levels of retinol binding protein which might help you get results quicker, but on the other hand "the oxidative conversion of retinol to retinal that requires the action of a
zinc-dependent retinol dehydrogenase enzyme" as they mention in the paper "Interactions between zinc and vitamin A: an update", although since soylent is so carefully balanced I'm not sure how safe it is to adjust zinc levels. Some papers that might interest you: "Inhibition of retinol oxidation by ethanol in the rat liver and colon", "Contribution of NADH increases to ethanol's inhibition of retinol oxidation by human ADH isoforms", "The Action of 11-cis-Retinol on Cone Opsins and Intact Cone Photoreceptors", "Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of cellular retinaldehyde-binding protein." I hope this information is helpful, Good luck ! This is an amazing project and I'm glad to be able to contribute to it.

[Cassox]

Awesome! Let me get back to this. Retinoic acid supplementation is already part of our protocol, but I'll have to check with the guy who's our liason with soylent regarding zinc and lycopene. I relatively sure lycopenes been excluded, but I'll double check. See, I was going with a way to inhibit retinol dehydrogenase at first, but since we're looking to jump straight to implementation with humans I kind of wrote off this angle as It would deserve animal experimentation first. The solution I've come up with to shorten the VAD time is to cycle total retinoid deficiency and retinoic acid supplementation. There was a study showing this to be efficacious in depleting reserves of Retinol. Ughlll... need coffee. Will have a reply with more coherence soon, but thank you for this reply. It's given me a few things to consider and work with.

[telight]

I would be very interested to know how you are planning to extract/synthesize/obtain the Vitamin A2 (3,4-dehydroretinol). I would be willing to make a generous contribution to your project if you could send me a test supply for my lab rats. If you are not comfortable with this, I would still be interested to know how you obtained your Vitamin A2.

[archangel]

Anyone tried supplementation with chlorin e6?

--

[robosapiens]

Have you tried eyedrops yet?

[allstargajo]

I'm sure that by now you have already searched the net high and low regarding this topic but for those that didn't, here's a link to why I'm skeptic about what you what to achieve. That been said, there's an anecdotal story regarding Monet and that following a cataract surgery he had his eye's lens removed and started seeing UV wavelengths, so you never know...

Best of luck to your endeavor and hope you get back to post some feedback when the experiment is done.

[archangel]

http://www.dtic.mil/.../u2/a441061.pdf

http://dare.uva.nl/document/24761

Someone who is not slightly drunk can interpret the results of these studies. All I see are squiggly lines and numbers.

But for reference...700-1,000nm is the common spectral sensitivity range of modern electronic nightvision.

See: http://www.gamma-sci...-Scientific.pdf


A.