2014
DOI: 10.1016/b978-0-12-417197-8.00001-8
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Constitutively Active Rhodopsin and Retinal Disease

Abstract: Rhodopsin is the light receptor in rod photoreceptor cells of the retina that initiates scotopic vision. In the dark, rhodopsin is bound to the chromophore 11-cis retinal, which locks the receptor in an inactive state. The maintenance of an inactive rhodopsin in the dark is critical for rod photoreceptor cells to remain highly sensitive. Perturbations by mutation or absence of 11-cis retinal can cause rhodopsin to become constitutively active, which leads to the desensitization of photoreceptor cells and, in s… Show more

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Cited by 56 publications
(64 citation statements)
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References 179 publications
(303 reference statements)
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“…It is generally assumed that retinoschisin and rhodopsin are retinaspecific proteins that are locally produced. 9,12,13,[18][19][20] This assumption is supported by our finding of higher mRNA levels of retinoschisin in donor retina than in plasma of DME patients. Limitations of this study include the fact that patients had been treated with either bevacizumab or ranibizumab, and our results may have been influenced by that particular anti-VEGF agent.…”
Section: Discussionsupporting
confidence: 79%
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“…It is generally assumed that retinoschisin and rhodopsin are retinaspecific proteins that are locally produced. 9,12,13,[18][19][20] This assumption is supported by our finding of higher mRNA levels of retinoschisin in donor retina than in plasma of DME patients. Limitations of this study include the fact that patients had been treated with either bevacizumab or ranibizumab, and our results may have been influenced by that particular anti-VEGF agent.…”
Section: Discussionsupporting
confidence: 79%
“…Dysfunction of rhodopsin by various mechanisms can cause a variety of human retinal diseases, including Leber congenital amaurosis and retinitis pigmentosa. 20 Our finding may be related to higher amounts of active rod cells in DME patients with better visual acuity and increased levels of mRNA rhodopsin to increase chances of rod cell survival. Subsequently, the mRNA may be released across the blood-retina barrier through openings of endothelial intercellular junctions and endothelial caveolar transcellular transport and then could be detected in the circulation.…”
Section: Discussionmentioning
confidence: 88%
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“…The Rpe65 upregulation, however, required high doses of TO9 (50 and 75 mg/kg BW) suggesting indirect regulation by LXRs. Because LXRs serve as cholesterol/oxysterol sensors, and increased cholesterol content is known to inhibit the activation of rhodopsin, another essential protein in the visual cycle ( 80,81 ), the TO9 upregulation of Rpe65 could be a mechanism protecting the function of rhodopsin in response to the elevation of retinal cholesterol. Indeed, cholesterol inhibits rhodopsin indirectly by ordering the lipid bilayer and limiting the ability of this membranebound enzyme to undergo conformational changes in the Supplemental Material can be found at:…”
Section: Discussionmentioning
confidence: 99%
“…Any increase in the level of the dark activity of rhodopsin reduces the signal-to-noise ratio affecting the light-sensing capability of the rod cells. Thus, constitutive activity in rhodopsin has been discussed as the cause of diseases (for a recent review [4]), such as retinitis pigmentosa (RP) [5,6] or congenital stationary night blindness (CSNB) [7,8]. RP is a progressive form of blindness that severely impairs the visual field, whereas CSNB is a much milder and often precursor form affecting only dim light vision.…”
Section: à11mentioning
confidence: 99%