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Retinoid metabolism in the eye

Published 12 September 2007, 05:08 PM

Our regular reader RocketRoo has recently contributed an interesting comment to the post on non-local realism of last April. A long time has past since then, and as this comment is more of a two-post than a comment, I am taking the liberty to repost it here. This is the second part:

RETINOID METABOLISM IN THE EYE

The arrangement of the retina is like connecting a bunch of CCDs such that all the connecting wires lie in front between the light source and the detectors. (See http://thalamus.wustl.edu/course/eyeret.html, and http://en.wikipedia.org/wiki/Retina for more background).

The metabolism behind photo-detection in the eye involves a kind of charge-discharge cycle, similar to the ATP (adenosine triphosphate) cycle used in bioluminescence (photo-production vs. photo-detection) e.g., fireflies. The chemical energy barrier is lowered via the clever use of enzymes (luciferase in the case of the firefly) . In vision chemistry, the enzyme is lecithin:retinol acyltransferase (aka LRAT). (See http://webvision.med.utah.edu/ for an animation).

Vitamin A and retinene, the carotenoid precursors of rhodopsin, occur in a variety of molecular shapes, cis-trans isomers of one another. For the synthesis of rhodopsin a specific cis isomer of vitamin A is needed. Ordinary crystalline vitamin A, as also the commercial synthetic product, both primarily all-trans, are ineffective. Vitamin A is an isomer aka all-trans-retinol. The -ol ending means the molecule overall acts like an alcohol. It is synthesized in the human body from precursor compounds like beta-carotene (a carotenoid), which is why carrots are suggested to improve night vision. The major role for vitamin A in the eye is to provide the chromophore of the visual pigment, the molecule responsible for the detection of incoming photons.

For more details on cis/trans isomers, see http://www.chemguide.co.uk/basicorg/isomerism/geometric.html. The cis-trans conversion in rhodopsin occurs in picoseconds! (see http://adsabs.harvard.edu/abs/1977Natur.269..179G)

Esterification is the process of combining an alcohol with an acid. An ester can be thought of as the organic analog of a salt. An inorganic salt is formed by reacting a base (e.g., sodium hydroxide) with an acid (e.g., sulfuric acid) to produce sodium sulphate and water. In biological systems, the acid is often a carboxylic acid (e.g., vinegar: acetic acid) and the base is replaced by an alcohol (in the organic chemistry sense). The esterification of ethanol (common "alcohol") and acetic acid produces ethyl acetate, which gives certain wines their fruity aroma.

The visual pigment is composed of a chromophore, 11-cis-retinal (the corresponding aldehyde), covalently linked to a protein, opsin, and is concentrated in the outer parts of the rod and cone photoreceptors; the cells responsible for the conversion of light to an electrical signal. Light isomerizes the rhodopsin retinyl chromophore into an all-trans configuration. The chromophore is released and reduced in the rod to form all-trans-retinol. All-trans-retinol is transported to the retinal pigment epithelial cells, where it is esterified by LRAT. All-trans-retinyl esters are stored in the retinosomes and/or utilized for production of 11-cis-retinol through enzymatic hydrolysis and isomerization. Oxidation of 11-cis-retinol to retinal, the subsequent transport to rod outer segments, and binding to opsin complete the cycle.

Credits: RocketRoo

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This issue of Cell (online pub http://www.cell.com/content/issue?volume=130&issue=3), contains a lead article entitled "Disc Membrane Biogenesis in Mammalian Photoreceptors" which reports on how light-sensing discs in the retina's rod cells regenerate themselves.

Rod cells contain tiny organelles called the 'outer segment,' which contain about 1,000 flattened discs containing rhodopsin -- a visual pigment that absorbs light. Each day, our eyes shed the top 10 percent of these discs, but until now, no one really knew how the retina generated new discs. "We believe we have solved that riddle." claims one of the authors. The rod cell's outer segment is constantly pushing up and forming new discs in a bottom-up process as older discs get shed at the segment's tip. There were theories as to how this might occur, but no hard evidence to back any of them up. The research team discovered that the new light-sensing discs are formed by the fusion, at the base of the outer segment, of rhodopsin vesicles. "This fusion makes a kind of preliminary disc, and then this disc matures and grows until it joins the hundreds of other discs on the rod cell's outer segment," Dr. Sung says. "All of this happens with the help of a regulating protein called the 'Smad Anchor for Receptor Activation' (SARA)," she adds.

Aside: I wonder how much this differs from how hair cells grow. I don't mean this facetiously. Sometimes, researchers are so focused on their own specialty, they fail to see similarities with other areas. For example, Alexander Tsiaras claims (See e.g., http://jama.ama-assn.org/cgi/content/full/293/23/2847) there are 7 repeated anatomical forms: tributaries (brancing)...networks, valves(?), and ???? Unfortunately, I've never been able to find the complete list of 7 forms; even in his published books. If anyone knows these, I would be interested to see the list. Could retinal regeneration be considered as one of these forms?

Main article on the Retina can be found at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-4PCRH3P-J&_user=10&_coverDate=08%2F10%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4bfb751e3bbd5294fef36680f3e2e428

# Friday, September 14, 2007 05:23 PM by redrooz_at_yahoo_com

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