610:. In this pathway, cones reduce all-trans retinal to all-trans retinol via all-trans Retinol Dehydrogenase, then transport all-trans retinol to Müller cells. There, it is transformed into 11-cis retinol by all-trans retinol isomerase, and can either be stored as retinyl esters within Müller cells, or transported back to the cone photoreceptors, where it is transformed from 11-cis retinol to 11-cis retinal by 11-cis Retinal Dehydrogenase. This pathway helps explain the rapid dark adaptation in the cone system, and the presence of 11-cis Retinal Dehydrogenase in cone photoreceptors, as it is not found in rods, only in the RPE.
22:
288:
677:. Without the RPE65 protein, the RPE is unable to store retinyl esters, and the visual cycle is therefore interrupted. At the beginning stages of the disease, the cone cells are unaffected, as they can rely on the alternate Muller cell visual cycle. However, rods do not have access to this alternative and are rendered inert. LCA therefore manifests as
689:, a neurotransmitter, at a rate the Muller cells are unable to absorb. The glutamate levels will build up within the retina, where they will reach neurotoxic levels. The RPE65 deficiency would be genetic in origin, and is only one of many proposed possible pathophysiologies of the disease. However, there is a
588:
system. When light activates the RGR-opsin, the recycling of chromophore in the RPE is accelerated. This mechanism provides additional chromophore after intense bleaches, and can be seen as an important mechanism in the early phases of dark adaptation and chromophore replenishment.
279:, for several reasons. Retinoids are toxic, insoluble in aqueous solutions, and prone to oxidation, and as such they must be bound and protected when within the body. The body uses a variety of chaperones, particularly in the retina, to transport retinoids.
567:
Under normal circumstances, the spent chromophore is discharged from the protein by an incoming "recharged" chromophore. However, sometimes the spent chromophore may leave the opsin protein prior to its replacement, when it is bound to the
576:-retinol, and then leaves the photoreceptor outer segment via the IRBP chaperone. It then follows the conventional visual cycle. It is from this pathway that the presence of opsin without a chromophore can be explained.
531:. It is in this form that the RPE stores most of its retinoids, as the RPE stores 2-3 times more retinoids than the neural retina itself. When further chromophore is required, the retinyl esters are acted on by
886:
Kolb H, Fernandez E, Nelson R (1995-01-01). "Melanopsin-expressing, Intrinsically
Photosensitive Retinal Ganglion Cells (IpRGCs)". In Kolb H, Fernandez E, Nelson R (eds.).
628:
619:
532:
492:. It will not leave the opsin protein until another fresh chromophore comes to replace it, except for in the ABCR pathway. Whilst still bound to the opsin, all-
248:, the transport and storage form of vitamin A. During the visual cycle, retinal moves between several different isomers and is also converted to retinol and
556:
513:
182:
911:
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524:
453:
670:
540:
43:
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39:
58:
548:
65:
941:
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516:(IRBP). It then enters the RPE cells, and is transferred to the Cellular Retinol Binding Protein (CRBP) chaperone.
509:
465:
162:
32:
222:
143:
702:
72:
936:
261:
931:
54:
399:(rhodopsin + hν → photorhodopsin → bathorhodopsin → lumirhodopsin → metarhodopsin I → metarhodopsin II);
740:
226:
210:
946:
559:. There, it replaces the spent chromophore in opsin molecules, rendering the opsin photosensitive.
527:(LRAT) to form a retinyl ester. The retinyl esters of the RPE are chaperoned by a protein known as
552:
505:
389:
276:
218:
158:
150:
893:
868:
819:
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681:(night blindness). In the later stages of the disease, general retinopathy is observed as the
418:
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127:
858:
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retinal itself when stimulated with another photon. An ipRGC therefore does not rely on
863:
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as it is ejected from the opsin protein. Each molecule of retinal must travel from the
727:
Moiseyev, Gennadiy; Chen, Ying; Takahashi, Yusuke; Wu, Bill X.; Ma, Jian-xing (2005).
504:-Retinol Dehydrogenase. It then proceeds to the cell membrane of the rod, where it is
925:
854:
707:
434:
404:
382:
275:
As in transport via the RBP-Transthyretin pathway, retinoids must always be bound to
265:
257:
249:
631:(ipRGC) also with a retinal chromaphore. However, unlike the rod and cone pigments,
788:"Role of LRAT on the Retinoid Isomerase Activity and Membrane Association of Rpe65"
355:
230:
693:
to reintroduce normal RPE65 genes that has been approved by the FDA since 2017.
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253:
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131:
21:
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and back in order to be refreshed and combined with another opsin. This closed
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by itself, but requires to be bound to an opsin protein to both trigger the
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872:
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protein (also known as ABCR). At this stage, it is also transformed to all-
287:
682:
461:
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685:
lose their ability to signal. As a result, the rods continually secrete
329:
245:
194:
123:
914:. FDA Center for Biologics Evaluation and Research. 19 December 2017.
477:
378:
371:
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139:
635:
has the ability to act as both the excitable photopigment and as a
602:
It is believed that an alternative visual cycle exists, which uses
786:
Jin, Minghao; Yuan, Quan; Li, Songhua; Travis, Gabriel H. (2007).
674:
569:
528:
323:
286:
214:
135:
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or can be consumed directly. To reach the retina, it is bound to
15:
729:"RPE65 is the isomerohydrolase in the retinoid visual cycle"
889:
122:
is a process in the retina that replenishes the molecule
837:Wang, Jin-Shan; Kefalov, Vladimir J. (March 2011).
46:. Unsourced material may be challenged and removed.
629:Intrinsically photosensitive retinal ganglion cell
620:Intrinsically photosensitive retinal ganglion cell
519:When inside the RPE cell, bound to CRBP, the all-
252:. Retinoids can be derived from the oxidation of
733:Proceedings of the National Academy of Sciences
547:-Retinol is transformed into 11-cis retinal by
586:retinal G-protein-coupled Receptor (RGR-opsin)
892:. University of Utah Health Sciences Center.
8:
639:. Melanopsin is therefore able to isomerize
185:in 1967 for his work towards its discovery.
514:Interphotoreceptor retinoid-binding protein
488:-retinal, and it moves to the exit site of
862:
813:
803:
762:
752:
584:The visual cycle can be regulated by the
213:when covalently bound to proteins called
106:Learn how and when to remove this message
719:
673:has been proposed as the deficiency of
268:, which prevents its filtration in the
541:Cellular retinaldehyde binding protein
539:-retinol, which is transferred to the
295:The visual cycle is consistent within
7:
843:Progress in Retinal and Eye Research
658:
229:to longer wavelengths, which enable
44:adding citations to reliable sources
244:. Retinal is interconvertible with
146:. When the photon is absorbed, the
14:
551:, then it is shipped back to the
496:-retinal is transformed into all-
454:lecithin retinol acyltransferases
855:10.1016/j.preteyeres.2010.11.001
839:"The Cone-specific visual cycle"
525:Lecithin Retinol Acyltransferase
299:, and is summarized as follows:
20:
792:Journal of Biological Chemistry
484:-retinal is transformed to all-
31:needs additional citations for
912:"Approved Products – Luxturna"
460:Steps 3, 4, 5, and 6 occur in
181:(1906–1997), who received the
1:
627:is a visual opsin present in
464:; Steps 1, 2, and 7 occur in
671:Leber's congenital amaurosis
659:Leber's congenital amaurosis
549:11-cis-retinol dehydrogenase
444:-retinol + fatty acid → all-
655:cells for this conversion.
963:
665:Leber congenital amaurosis
662:
653:retinal pigment epithelium
617:
608:Retinal Pigment Epithelium
598:Cone-specific visual cycle
523:-retinol is esterified by
510:Retinal Pigment Epithelium
466:retinal pigment epithelium
192:
138:, meaning it captures the
669:A possible mechanism for
240:and the aldehyde form of
223:phototransduction cascade
144:phototransduction cascade
703:Visual phototransduction
344:-retinol dehydrogenases;
340:-retinal + NADH + H; 11-
236:Retinal is a species of
754:10.1073/pnas.0503460102
614:Melanopsin visual cycle
462:rod cell outer segments
411:O → aporhodopsin + all-
262:Retinol Binding Protein
805:10.1074/jbc.M701432200
292:
429:-retinol + NADP; all-
290:
211:Retinylidene proteins
691:retinal gene therapy
227:spectral sensitivity
173:is sometimes called
40:improve this article
798:(29): 20915–20924.
745:2005PNAS..10212413M
739:(35): 12413–12418.
553:photoreceptor cells
277:Chaperone molecules
175:Wald's visual cycle
604:Müller glial cells
593:Alternative cycles
448:-retinyl ester + H
425:+ NADPH + H → all-
326:isomerohydrolases;
293:
159:photoreceptor cell
942:Sensory receptors
217:. Retinal can be
167:enzymatic pathway
155:all-trans retinal
130:. Retinal is the
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533:isomerohydrolase
500:-retinol by all-
480:is absorbed, 11-
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390:photoisomerizes
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219:photoisomerized
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151:photoisomerizes
134:of most visual
126:for its use in
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937:Nervous system
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849:(2): 115–128.
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663:Main article:
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618:Main article:
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580:RGR regulation
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535:to produce 11-
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308:-retinyl ester
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208:photosensitive
193:Main article:
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171:11-cis retinal
148:11-cis retinal
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55:"Visual cycle"
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643:retinal into
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543:(CRALBP). 11-
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468:(RPE) cells.
467:
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405:metarhodopsin
403:
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385:II (i.e., 11-
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383:metarhodopsin
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267:
266:Transthyretin
263:
259:
258:beta carotene
255:
251:
250:retinyl ester
247:
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225:and tune the
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51:Find sources:
45:
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29:This article
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649:Müller cells
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563:ABCR pathway
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377:rhodopsin +
356:aporhodopsin
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291:Visual cycle
274:
235:
231:color vision
199:
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120:visual cycle
119:
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69:
62:
50:
38:Please help
33:verification
30:
606:instead of
472:Description
370:linkage to
368:Schiff base
336:+ NAD → 11-
318:-retinol +
254:carotenoids
206:that forms
204:chromophore
183:Nobel Prize
179:George Wald
132:chromophore
947:Metabolism
926:Categories
714:References
679:nyctalopia
641:all-trans-
633:melanopsin
625:Melanopsin
506:chaperoned
374:, -CH=NH-;
320:fatty acid
264:(RBP) and
66:newspapers
687:glutamate
683:rod cells
512:(RPE) by
490:rhodopsin
433:-retinol
415:-retinal;
366:O; forms
360:rhodopsin
270:glomeruli
242:Vitamin A
898:21413389
873:21111842
824:17504753
773:16116091
697:See also
456:(LRATs).
423:-retinal
352:-retinal
334:-retinol
283:Overview
238:retinoid
96:May 2017
864:3073571
815:2747659
764:1194921
741:Bibcode
651:and/or
645:11-cis-
508:to the
476:When a
392:to all-
314:O → 11-
297:mammals
246:retinol
200:Retinal
195:Retinal
189:Retinal
161:to the
140:photons
124:retinal
80:scholar
896:
871:
861:
822:
812:
771:
761:
478:photon
407:II + H
372:lysine
215:opsins
177:after
136:opsins
128:vision
82:
75:
68:
61:
53:
675:RPE65
574:trans
570:ABCA4
529:RPE65
521:trans
502:trans
498:trans
494:trans
486:trans
446:trans
442:trans
431:trans
427:trans
421:trans
413:trans
394:trans
324:RPE65
306:trans
256:like
202:is a
153:into
87:JSTOR
73:books
894:PMID
869:PMID
820:PMID
769:PMID
557:IRBP
555:via
440:all-
419:all-
304:all-
118:The
59:news
859:PMC
851:doi
810:PMC
800:doi
796:282
759:PMC
749:doi
737:102
545:cis
537:cis
482:cis
452:O;
396:):
387:cis
362:+ H
350:cis
348:11-
342:cis
338:cis
332:cis
330:11-
316:cis
310:+ H
169:of
163:RPE
42:by
928::
867:.
857:.
847:30
845:.
841:.
818:.
808:.
794:.
790:.
767:.
757:.
747:.
735:.
731:.
381:→
379:hν
358:→
354:+
322:;
272:.
233:.
900:.
875:.
853::
826:.
802::
775:.
751::
743::
450:2
437:;
409:2
364:2
312:2
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103:(
98:)
94:(
84:·
77:·
70:·
63:·
36:.
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