The Biochemistry of the Visual Process
For vision to be a continuous process the photoreceptors (rods and cones) must continually regenerate 11-cis retinal. Rods and cones have slightly different ways of doing this. WARNING: this is only for the extremely nerdy. If you aren't very interested in the biochemical processing of vitamin A in the retina, this entry probably isn't for you.
For rods:
A photon (light ray) is absorbed by pigment within the opsin in the outer segment of the photoreceptor cell. Inside the activated opsin, 11-cis retinal is converted to all-trans retinal and released to the disc of the inner segment of the photoreceptor.
Within the disc, all-trans retinal binds phosphatidylethanolamine. This produces N-retinylidine-phosphatidyl-ethanolamine (NRPE). ATP binding cassette transporter carries the NRPE complex to the cell membrane of the disc. At the cell membrane the all-trans retinal portion of the NRPE complex is transported to the cytoplasm within the cell body of the photoreceptor.
Inside the cell body of the photoreceptor, the all-trans retinal binds all-trans retinol dehydrogenase (AT-RDH), which obtains NADPH to reduce all-trans retinal to all-trans retinol. The resulting all-trans retinol is taken from the cell body of a photoreceptor to the inside of a retinal pigmented epithelium (RPE) cell by interphotoreceptor retinoid binding protein (IRBP).
Inside the RPE cell, the all-trans retinol binds the cellular retinoid binding protein (CRBP), which delivers the all-trans retinol to lecithin retinol acyl transferase (LRAT). The enzyme, LRAT binds phosphatidyl choline to the all-trans retinol to produce all-trans retinyl, or the ester storage form of retinoids. Defects in the gene producing LRAT have been associated with retinitis pigmentosa.
Having sufficient retinyl stores improves night vision. Retinyl stores can be improved by getting enough vitamin A in one's diet. Spinach is a great natural source for vitamin A (even better than carrots). Smokers should avoid large amounts of vitamin A, since it has been linked to an increased risk of lung cancer in this population.
The all-trans retinyl is bound by the protein RPE65 and activates the enzyme isomerohydrolase. The all-trans retinyl is hydrolyzed and isomerized to produce 11-cis retinol. RPE65 is required to activate stored retinoids and recharge the phototransduction process. Defects in the gene that produce RPE65 have been associated with Leber's congenital amaurosis and retinitis pigmentosa.
Cellular retinaldehyde binding protein (CRALBP) binds the resulting 11-cis retinol and delivers it to 11-cis retinal dehydrogenase (11-CRDH). NAD is utlized by 11-CRDH to oxidize 11-cis retinol to 11-cis retinal. Finally, IRBP delivers the regenerated 11-cis retinal back to the outer segment of the photoreceptor, so the process can start all over again.
For cones the process is slightly different and not completely understood. Cones are constantly firing throughout the day, as they are continually exposed to light rays.
Cones rely upon Mueller cells to speed up 11-cis retinal regeneration. The process starts the same, with 11-cis retinal being converted to all-trans retinol. The process changes when the all-trans retinol is diverted to those Mueller cells. Inside the Mueller cells, all-trans retinol is isomerized back to 11-cis retinol. The 11-cis retinol is sent back to the inner segment of the cone photoreceptors.
Inside the inner segment the 11-cis retinol is oxidized back to 11-cis retinal. Most enzymes involved in the process are unknown, but IRBP is involved in transport between the cones and Mueller cells and CRALBP is present within Mueller cells to bind 11-cis retinol.
Summary
Rods and cones have different mechanisms to regenerate 11-cis retinal.
The RPE helps recharge rods and Mueller cells help recharge cones.
Spinach (vitamin A) improves retinyl stores and night vision for non-smokers.
RPE65 and LRAT are vital proteins being targeted for gene therapy for Leber's congenital amaurosis, retinitis pigmentosa and Stargardt's.
For rods:
A photon (light ray) is absorbed by pigment within the opsin in the outer segment of the photoreceptor cell. Inside the activated opsin, 11-cis retinal is converted to all-trans retinal and released to the disc of the inner segment of the photoreceptor.
Within the disc, all-trans retinal binds phosphatidylethanolamine. This produces N-retinylidine-phosphatidyl-ethanolamine (NRPE). ATP binding cassette transporter carries the NRPE complex to the cell membrane of the disc. At the cell membrane the all-trans retinal portion of the NRPE complex is transported to the cytoplasm within the cell body of the photoreceptor.
Inside the cell body of the photoreceptor, the all-trans retinal binds all-trans retinol dehydrogenase (AT-RDH), which obtains NADPH to reduce all-trans retinal to all-trans retinol. The resulting all-trans retinol is taken from the cell body of a photoreceptor to the inside of a retinal pigmented epithelium (RPE) cell by interphotoreceptor retinoid binding protein (IRBP).
Inside the RPE cell, the all-trans retinol binds the cellular retinoid binding protein (CRBP), which delivers the all-trans retinol to lecithin retinol acyl transferase (LRAT). The enzyme, LRAT binds phosphatidyl choline to the all-trans retinol to produce all-trans retinyl, or the ester storage form of retinoids. Defects in the gene producing LRAT have been associated with retinitis pigmentosa.
Having sufficient retinyl stores improves night vision. Retinyl stores can be improved by getting enough vitamin A in one's diet. Spinach is a great natural source for vitamin A (even better than carrots). Smokers should avoid large amounts of vitamin A, since it has been linked to an increased risk of lung cancer in this population.
The all-trans retinyl is bound by the protein RPE65 and activates the enzyme isomerohydrolase. The all-trans retinyl is hydrolyzed and isomerized to produce 11-cis retinol. RPE65 is required to activate stored retinoids and recharge the phototransduction process. Defects in the gene that produce RPE65 have been associated with Leber's congenital amaurosis and retinitis pigmentosa.
Cellular retinaldehyde binding protein (CRALBP) binds the resulting 11-cis retinol and delivers it to 11-cis retinal dehydrogenase (11-CRDH). NAD is utlized by 11-CRDH to oxidize 11-cis retinol to 11-cis retinal. Finally, IRBP delivers the regenerated 11-cis retinal back to the outer segment of the photoreceptor, so the process can start all over again.
For cones the process is slightly different and not completely understood. Cones are constantly firing throughout the day, as they are continually exposed to light rays.
Cones rely upon Mueller cells to speed up 11-cis retinal regeneration. The process starts the same, with 11-cis retinal being converted to all-trans retinol. The process changes when the all-trans retinol is diverted to those Mueller cells. Inside the Mueller cells, all-trans retinol is isomerized back to 11-cis retinol. The 11-cis retinol is sent back to the inner segment of the cone photoreceptors.
Inside the inner segment the 11-cis retinol is oxidized back to 11-cis retinal. Most enzymes involved in the process are unknown, but IRBP is involved in transport between the cones and Mueller cells and CRALBP is present within Mueller cells to bind 11-cis retinol.
Summary
Rods and cones have different mechanisms to regenerate 11-cis retinal.
The RPE helps recharge rods and Mueller cells help recharge cones.
Spinach (vitamin A) improves retinyl stores and night vision for non-smokers.
RPE65 and LRAT are vital proteins being targeted for gene therapy for Leber's congenital amaurosis, retinitis pigmentosa and Stargardt's.
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