RDH12 Activity and Effects on Retinoid Processing in the Murine Retina.
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RDH12 Activity and Effects on Retinoid Processing in the Murine Retina. / Chrispell, Jared D; Feathers, Kecia L; Kane, Maureen A; Kim, Chul Y; Brooks, Matthew; Khanna, Ritu; Kurth, Ingo; Huebner, Christian A; Gal, Andreas; Mears, Alan J; Swaroop, Anand; Napoli, Joseph L; Sparrow, Janet R; Thompson, Debra A.
In: J BIOL CHEM, 2009.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - RDH12 Activity and Effects on Retinoid Processing in the Murine Retina.
AU - Chrispell, Jared D
AU - Feathers, Kecia L
AU - Kane, Maureen A
AU - Kim, Chul Y
AU - Brooks, Matthew
AU - Khanna, Ritu
AU - Kurth, Ingo
AU - Huebner, Christian A
AU - Gal, Andreas
AU - Mears, Alan J
AU - Swaroop, Anand
AU - Napoli, Joseph L
AU - Sparrow, Janet R
AU - Thompson, Debra A
PY - 2009
Y1 - 2009
N2 - RDH12 mutations are responsible for early-onset autosomal recessive retinal dystrophy that results in profound retinal pathology and severe visual handicap in patients. To investigate the function of RDH12 within the network of retinoid dehydrogenases/ reductases (RDHs) present in retina, we are studying the retinal phenotype of Rdh12-deficient mice. Rates of all-trans retinol and 11-cis retinal formation during recovery from bleaching were similar in Rdh12-deficient and wild-type mice matched for an Rpe65 polymorphism that impacts visual cycle efficiency. However, retinal homogenates from Rdh12-deficient mice exhibited markedly decreased capacity to reduce exogenous retinaldehydes in vitro. Furthermore, in vivo levels of the bisretinoid compound A2E were increased in Rdh12-deficient mice on various genetic backgrounds. Conversely, in vivo levels of retinoic acid and total retinol were significantly decreased. Rdh12 transcript levels in wild-type mice homozygous for the Rpe65-Leu450 polymorphism were greater than in Rpe65-Met450 mice, and increased during postnatal development in wild-type mice and Nrl-deficient mice having an all-cone retina. Rdh12-deficient mice did not exhibit increased retinal degeneration relative to wild-type mice at advanced ages, or when bred on the light-sensitive BALB/c background, or when heterozygous for a null allele of superoxide dismutase 2 (Sod2+/-). Our findings suggest that a critical function of RDH12 is the reduction of all-trans retinal that exceeds the reductive capacity of the photoreceptor outer segments.
AB - RDH12 mutations are responsible for early-onset autosomal recessive retinal dystrophy that results in profound retinal pathology and severe visual handicap in patients. To investigate the function of RDH12 within the network of retinoid dehydrogenases/ reductases (RDHs) present in retina, we are studying the retinal phenotype of Rdh12-deficient mice. Rates of all-trans retinol and 11-cis retinal formation during recovery from bleaching were similar in Rdh12-deficient and wild-type mice matched for an Rpe65 polymorphism that impacts visual cycle efficiency. However, retinal homogenates from Rdh12-deficient mice exhibited markedly decreased capacity to reduce exogenous retinaldehydes in vitro. Furthermore, in vivo levels of the bisretinoid compound A2E were increased in Rdh12-deficient mice on various genetic backgrounds. Conversely, in vivo levels of retinoic acid and total retinol were significantly decreased. Rdh12 transcript levels in wild-type mice homozygous for the Rpe65-Leu450 polymorphism were greater than in Rpe65-Met450 mice, and increased during postnatal development in wild-type mice and Nrl-deficient mice having an all-cone retina. Rdh12-deficient mice did not exhibit increased retinal degeneration relative to wild-type mice at advanced ages, or when bred on the light-sensitive BALB/c background, or when heterozygous for a null allele of superoxide dismutase 2 (Sod2+/-). Our findings suggest that a critical function of RDH12 is the reduction of all-trans retinal that exceeds the reductive capacity of the photoreceptor outer segments.
M3 - SCORING: Zeitschriftenaufsatz
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
ER -