The molecular basis of retinoic acid induced night blindness

Law, Wing Cheung; Rando, Robert R.

doi:10.1016/0006-291x(89)92674-0

Cited by 44 publications

(42 citation statements)

References 9 publications

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“…The resulting 11cROL is oxidized by 11cRDH to form 11cRAL chromophore. 11cRDH is inhibited by isotretinoin with a K i of Ϸ0.1 M (26,27). The Ki for inhibition of atRDH by isotretinoin is at least two logs higher (N.L.M., R.A.R., and G.H.T., unpublished observations).…”

Section: Methodsmentioning

confidence: 89%

“…Isotretinoin inhibits 11cRDH in RPE cells (26,27). We analyzed the kinetics of dark adaptation in isotretinoin-treated and untreated mice by ERG with bright and dim probe flashes.…”

Section: Discussionmentioning

confidence: 99%

“…Isotretinoin (13-cis-retinoic acid or Accutane) is a drug in common use for the treatment of acne (23). A side effect of treatment with isotretinoin is reduced night vision (24,25) because of its inhibitory effect on 11-cis-retinol dehydrogenase (11cRDH) in RPE cells (26,27) (Fig. 1A).…”

mentioning

confidence: 99%

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Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration

Radu

Mata

Nusinowitz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

148

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Section: Methodsmentioning

confidence: 89%

“…Isotretinoin inhibits 11cRDH in RPE cells (26,27). We analyzed the kinetics of dark adaptation in isotretinoin-treated and untreated mice by ERG with bright and dim probe flashes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration

Radu

Mata

Nusinowitz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

148

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“…An occasional side effect of Accutane ® is reduced night vision (196). This effect is due to its inhibitory effect on 11-cis-RDH in RPE cells (197,198) (Figure 5). Isotretinoin also binds to Rpe65 (199) and therefore might also inhibit the isomerase.…”

Section: Retinoid Inhibitors Of A2e Formationmentioning

confidence: 99%

Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents

Travis

Golczak

Moise

et al. 2007

Annu. Rev. Pharmacol. Toxicol.

368

452

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Absorption of a photon by an opsin pigment causes isomerization of the chromophore from 11-cisretinaldehyde to all-trans-retinaldehyde. Regeneration of visual chromophore following light exposure is dependent on an enzyme pathway called the retinoid or visual cycle. Our understanding of this pathway has been greatly facilitated by the identification of disease-causing mutations in the genes coding for visual cycle enzymes. Defects in nearly every step of this pathway are responsible for human-inherited retinal dystrophies. These retinal dystrophies can be divided into two etiologic groups. One involves the impaired synthesis of visual chromophore. The second involves accumulation of cytotoxic products derived from all-trans-retinaldehyde. Gene therapy has been successfully used in animal models of these diseases to rescue the function of enzymes involved in chromophore regeneration, restoring vision. Dystrophies resulting from impaired chromophore synthesis can also be treated by supplementation with a chromophore analog. Dystrophies resulting from the accumulation of toxic pigments can be treated pharmacologically by inhibiting the visual cycle, or limiting the supply of vitamin A to the eyes. Recent progress in both areas provides hope that multiple inherited retinal diseases will soon be treated by pharmaceutical intervention.

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“…Isotretinoin (13-cis retinoic acid) acts as a blocker of the visual cycle because it inhibits RDH activity (Law and Rando, 1989); it reduces retinal damage from constant light exposure ) and reduces accumulation of lipofuscin in ABCA2-deficient mice (Radu et al, 2003). Another retinoid analog that inhibits the visual cycle is N-(4-hydroxyphenyl)retinamide (HPR).…”

Section: The Visual Cyclementioning

confidence: 99%

Seeing the light: New insights into the molecular pathogenesis of retinal diseases

Campochiaro

2007

Journal Cellular Physiology

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In the past, most treatments for retinal diseases have been empirical. Steroids and/or laser photocoagulation and/or surgery have been tried for almost every condition with little or no understanding of the underlying disease. Over the past several years vision researchers have uncovered molecular components of processes, such as visual transduction and the visual cycle, that are critical for visual function, and identified other molecules that lead to dysfunction and disease processes such as neovascularization and macular edema. It is becoming clear that dysregulation of certain molecules can have major effects on retinal structure and function. Studies in animal models have suggested that inhibiting or augmenting levels of a single molecule can have major effects in complex disease processes. Although several molecules probably contribute to neovascularization and excessive vascular permeability in the eye, blockade of vascular endothelial growth factor (VEGF) has remarkable beneficial effects in animal models that have now been proven to apply to human diseases in clinical trials. Intraocular injection of VEGF antagonists has revolutionized the treatment of choroidal neovascularization (CNV) and macular edema and serves as a model of targeted ocular pharmacotherapy. Significant progress elucidating the molecular pathogenesis of several disease processes in the eye may soon lead to new treatments following the lead of VEGF antagonists. Initial treatments that provide benefit from frequent intraocular injections are likely to be followed by sustained delivery of drugs and/or prolonged protein delivery by gene transfer. The eye has entered the era of molecular therapy. J. Cell. Physiol. 213: 348–354, 2007. © 2007 Wiley‐Liss, Inc.

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The molecular basis of retinoic acid induced night blindness

Cited by 44 publications

References 9 publications

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration

Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents

Seeing the light: New insights into the molecular pathogenesis of retinal diseases

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