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Retinol dehydrogenase 13 protects the mouse retina from acute light damage.

Wang H, Cui X, Gu Q, Chen Y, Zhou J, Kuang Y, Wang Z, Xu X - Mol. Vis. (2012)

Bottom Line: We found that there was no obvious difference in phenotype or function between Rdh13 knockout and wild-type mice.Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 (Apaf-1) and caspases 3, and other mitochondria apoptosis-related genes (nuclear factor-kappa B P65 [P65] and B-cell lymphoma 2-associated X protein [Bax]) were observed in Rdh13(-/-) mice.The mechanism may involve inhibition of the mitochondrial apoptosis pathway.

View Article: PubMed Central - PubMed

ABSTRACT

Purpose: To investigate whether retinol dehydrogenase 13 (RDH13) can protect the retina from acute light-induced damage.

Methods: We generated Rdh13 knockout mice using molecular biologic methods and assessed the associated morphological and functional changes under room-light conditions by hematoxylin-eosin (H&E), transmission electron microscopy (TEM), and scotopic electroretinography. Then, the light-damage model was established by exposure to diffuse white light (3,000 lx) for 48 h. Twenty-four h after light exposure, H&E was used for the histological evaluation. The thickness of the outer-plus-inner-segment and the outer nuclear layer was measured on sections parallel to the vertical meridian of the eye. An electroretinography test was performed to assess the functional change. Furthermore, the impairment of mitochondria was detected by TEM. Finally, the expression of cytochrome c (CytC) and other apoptosis-related proteins was detected by western blot.

Results: We found that there was no obvious difference in phenotype or function between Rdh13 knockout and wild-type mice. In Rdh13(-/-) mice subjected to intense light exposure, the photoreceptor outer-plus-inner-segment and outer nuclear layer were dramatically shorter, and the amplitudes of a- and b-waves under scotopic conditions were significantly attenuated. Distinctly swollen mitochondria with disrupted cristae were observed in the photoreceptor inner segments of Rdh13(-/-) mice. Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 (Apaf-1) and caspases 3, and other mitochondria apoptosis-related genes (nuclear factor-kappa B P65 [P65] and B-cell lymphoma 2-associated X protein [Bax]) were observed in Rdh13(-/-) mice.

Conclusions: Rdh13 can protect the retina against acute light-induced retinopathy. The mechanism may involve inhibition of the mitochondrial apoptosis pathway.

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Related in: MedlinePlus

The visual cycle in the vertebrate retina. The classical visual cycle is a chain of biochemical reactions that are catalyzed by retinoid dehydrogenase/reductase (RDH) in photoreceptors or the retinal pigment epithelia (RPE) and are responsible for regenerating visual pigment following light exposure [28]. The visual process is initiated by the photoisomerization of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL). First, 11cRAL diffuses from the RPE to photoreceptor-rod outer segments (OS; rod outer segments, ROS; and cone outer segments, COS) and is coupled to opsin to generate rhodopsin (Rh; reaction a). Then, in the photoreceptor outer segments, the absorption of light by rhodopsin causes isomerization of the chromophore from the 11-cis form to the all-trans form (reaction b). The atRAL is reduced to all-trans-retinol (atROL) in the reaction catalyzed by an nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent all-trans-retinal-specific dehydrogenase (all-trans-RDH, RDH8, RDH12; reaction c) [8,22]. Next, atROL diffuses to the RPE, where it is esterified to all-trans-retinyl-ester (atRE) in a reaction catalyzed by lecithin: retinol acyltransferase (LRAT; reaction d). The isomerization of atRE to 11cROL is catalyzed by RPE-specific 65 kDa protein (RPE65; reaction e), which is the key step in the retinoid visual cycle [29-31]. 11cROL is then oxidized by 11-cis-RDH (RDH5, RDH11) to 11cRAL to complete the retinoid cycle (reaction f). IPM, interphotoreceptor matrix; IRBP, inter-photoreceptor retinol binding protein.
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f1: The visual cycle in the vertebrate retina. The classical visual cycle is a chain of biochemical reactions that are catalyzed by retinoid dehydrogenase/reductase (RDH) in photoreceptors or the retinal pigment epithelia (RPE) and are responsible for regenerating visual pigment following light exposure [28]. The visual process is initiated by the photoisomerization of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL). First, 11cRAL diffuses from the RPE to photoreceptor-rod outer segments (OS; rod outer segments, ROS; and cone outer segments, COS) and is coupled to opsin to generate rhodopsin (Rh; reaction a). Then, in the photoreceptor outer segments, the absorption of light by rhodopsin causes isomerization of the chromophore from the 11-cis form to the all-trans form (reaction b). The atRAL is reduced to all-trans-retinol (atROL) in the reaction catalyzed by an nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent all-trans-retinal-specific dehydrogenase (all-trans-RDH, RDH8, RDH12; reaction c) [8,22]. Next, atROL diffuses to the RPE, where it is esterified to all-trans-retinyl-ester (atRE) in a reaction catalyzed by lecithin: retinol acyltransferase (LRAT; reaction d). The isomerization of atRE to 11cROL is catalyzed by RPE-specific 65 kDa protein (RPE65; reaction e), which is the key step in the retinoid visual cycle [29-31]. 11cROL is then oxidized by 11-cis-RDH (RDH5, RDH11) to 11cRAL to complete the retinoid cycle (reaction f). IPM, interphotoreceptor matrix; IRBP, inter-photoreceptor retinol binding protein.

Mentions: Retinoid dehydrogenase/reductase (RDH) is a subfamily of the short-chain dehydrogenase/reductase family that participates in the metabolism of steroids, prostaglandins, and retinoids [1,2] and performs critical oxidation-reduction reactions during the retinoid cycle (Figure 1). RDH11–RDH14 share sequence similarity and RDH11 is strongly expressed in the retinal pigment epithelia (RPE) [3,4]; the other three all localize to the photoreceptor inner segment [5,6]. It has been demonstrated that 11-cis-RDHs (RDH5, RDH11) can catalyze the oxidation of 11-cis-retinol to 11-cis-retinal [7]. All-trans-RDHs (RDH8, RDH12, and RDH14) have very similar properties and can catalyze the reduction of all-trans-retinal to all-trans-retinol [5,8-10]. Haeseleer reported that RDH13 lacks RDH activity [5]. Recently, Belyaeva [11] showed that purified RDH13 can recognize all-trans-retinaldehydes as substrate in vitro, with nicotinamide-adenine dinucleotide phosphate (NADPH) as the preferred cofactor, and can exhibit catalytic activity as a reductase. Kinetic analysis revealed that RDH13 exhibited substrate and cofactor specificity similar to that of RDH11, RDH12, and RDH14, but exhibited greater catalytic efficiency in the reduction of all-trans-retinal to all-trans-retinol than in the oxidation of these compounds [11].Thus, RDH13 is considered to participate in the retinoid cycle, and it may be involved in the clearance of all-trans-retinal.


Retinol dehydrogenase 13 protects the mouse retina from acute light damage.

Wang H, Cui X, Gu Q, Chen Y, Zhou J, Kuang Y, Wang Z, Xu X - Mol. Vis. (2012)

The visual cycle in the vertebrate retina. The classical visual cycle is a chain of biochemical reactions that are catalyzed by retinoid dehydrogenase/reductase (RDH) in photoreceptors or the retinal pigment epithelia (RPE) and are responsible for regenerating visual pigment following light exposure [28]. The visual process is initiated by the photoisomerization of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL). First, 11cRAL diffuses from the RPE to photoreceptor-rod outer segments (OS; rod outer segments, ROS; and cone outer segments, COS) and is coupled to opsin to generate rhodopsin (Rh; reaction a). Then, in the photoreceptor outer segments, the absorption of light by rhodopsin causes isomerization of the chromophore from the 11-cis form to the all-trans form (reaction b). The atRAL is reduced to all-trans-retinol (atROL) in the reaction catalyzed by an nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent all-trans-retinal-specific dehydrogenase (all-trans-RDH, RDH8, RDH12; reaction c) [8,22]. Next, atROL diffuses to the RPE, where it is esterified to all-trans-retinyl-ester (atRE) in a reaction catalyzed by lecithin: retinol acyltransferase (LRAT; reaction d). The isomerization of atRE to 11cROL is catalyzed by RPE-specific 65 kDa protein (RPE65; reaction e), which is the key step in the retinoid visual cycle [29-31]. 11cROL is then oxidized by 11-cis-RDH (RDH5, RDH11) to 11cRAL to complete the retinoid cycle (reaction f). IPM, interphotoreceptor matrix; IRBP, inter-photoreceptor retinol binding protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3351414&req=5

f1: The visual cycle in the vertebrate retina. The classical visual cycle is a chain of biochemical reactions that are catalyzed by retinoid dehydrogenase/reductase (RDH) in photoreceptors or the retinal pigment epithelia (RPE) and are responsible for regenerating visual pigment following light exposure [28]. The visual process is initiated by the photoisomerization of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL). First, 11cRAL diffuses from the RPE to photoreceptor-rod outer segments (OS; rod outer segments, ROS; and cone outer segments, COS) and is coupled to opsin to generate rhodopsin (Rh; reaction a). Then, in the photoreceptor outer segments, the absorption of light by rhodopsin causes isomerization of the chromophore from the 11-cis form to the all-trans form (reaction b). The atRAL is reduced to all-trans-retinol (atROL) in the reaction catalyzed by an nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent all-trans-retinal-specific dehydrogenase (all-trans-RDH, RDH8, RDH12; reaction c) [8,22]. Next, atROL diffuses to the RPE, where it is esterified to all-trans-retinyl-ester (atRE) in a reaction catalyzed by lecithin: retinol acyltransferase (LRAT; reaction d). The isomerization of atRE to 11cROL is catalyzed by RPE-specific 65 kDa protein (RPE65; reaction e), which is the key step in the retinoid visual cycle [29-31]. 11cROL is then oxidized by 11-cis-RDH (RDH5, RDH11) to 11cRAL to complete the retinoid cycle (reaction f). IPM, interphotoreceptor matrix; IRBP, inter-photoreceptor retinol binding protein.
Mentions: Retinoid dehydrogenase/reductase (RDH) is a subfamily of the short-chain dehydrogenase/reductase family that participates in the metabolism of steroids, prostaglandins, and retinoids [1,2] and performs critical oxidation-reduction reactions during the retinoid cycle (Figure 1). RDH11–RDH14 share sequence similarity and RDH11 is strongly expressed in the retinal pigment epithelia (RPE) [3,4]; the other three all localize to the photoreceptor inner segment [5,6]. It has been demonstrated that 11-cis-RDHs (RDH5, RDH11) can catalyze the oxidation of 11-cis-retinol to 11-cis-retinal [7]. All-trans-RDHs (RDH8, RDH12, and RDH14) have very similar properties and can catalyze the reduction of all-trans-retinal to all-trans-retinol [5,8-10]. Haeseleer reported that RDH13 lacks RDH activity [5]. Recently, Belyaeva [11] showed that purified RDH13 can recognize all-trans-retinaldehydes as substrate in vitro, with nicotinamide-adenine dinucleotide phosphate (NADPH) as the preferred cofactor, and can exhibit catalytic activity as a reductase. Kinetic analysis revealed that RDH13 exhibited substrate and cofactor specificity similar to that of RDH11, RDH12, and RDH14, but exhibited greater catalytic efficiency in the reduction of all-trans-retinal to all-trans-retinol than in the oxidation of these compounds [11].Thus, RDH13 is considered to participate in the retinoid cycle, and it may be involved in the clearance of all-trans-retinal.

Bottom Line: We found that there was no obvious difference in phenotype or function between Rdh13 knockout and wild-type mice.Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 (Apaf-1) and caspases 3, and other mitochondria apoptosis-related genes (nuclear factor-kappa B P65 [P65] and B-cell lymphoma 2-associated X protein [Bax]) were observed in Rdh13(-/-) mice.The mechanism may involve inhibition of the mitochondrial apoptosis pathway.

View Article: PubMed Central - PubMed

ABSTRACT

Purpose: To investigate whether retinol dehydrogenase 13 (RDH13) can protect the retina from acute light-induced damage.

Methods: We generated Rdh13 knockout mice using molecular biologic methods and assessed the associated morphological and functional changes under room-light conditions by hematoxylin-eosin (H&E), transmission electron microscopy (TEM), and scotopic electroretinography. Then, the light-damage model was established by exposure to diffuse white light (3,000 lx) for 48 h. Twenty-four h after light exposure, H&E was used for the histological evaluation. The thickness of the outer-plus-inner-segment and the outer nuclear layer was measured on sections parallel to the vertical meridian of the eye. An electroretinography test was performed to assess the functional change. Furthermore, the impairment of mitochondria was detected by TEM. Finally, the expression of cytochrome c (CytC) and other apoptosis-related proteins was detected by western blot.

Results: We found that there was no obvious difference in phenotype or function between Rdh13 knockout and wild-type mice. In Rdh13(-/-) mice subjected to intense light exposure, the photoreceptor outer-plus-inner-segment and outer nuclear layer were dramatically shorter, and the amplitudes of a- and b-waves under scotopic conditions were significantly attenuated. Distinctly swollen mitochondria with disrupted cristae were observed in the photoreceptor inner segments of Rdh13(-/-) mice. Increased expression levels of CytC, CytC-responsive apoptosis proteinase activating factor-1 (Apaf-1) and caspases 3, and other mitochondria apoptosis-related genes (nuclear factor-kappa B P65 [P65] and B-cell lymphoma 2-associated X protein [Bax]) were observed in Rdh13(-/-) mice.

Conclusions: Rdh13 can protect the retina against acute light-induced retinopathy. The mechanism may involve inhibition of the mitochondrial apoptosis pathway.

Show MeSH
Related in: MedlinePlus