Long-term effects of fenretinide on retinal function

DeCensi, Andrea; Fontana, Vincenzo; Fioretto, M.; Rondanina, Gabriella; Torrisi, Rosalba; Orengo, Maria Antonietta; Costa, Alberto

doi:10.1016/s0959-8049(96)00351-6

Cited by 27 publications

(9 citation statements)

References 19 publications

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“…Clinically, investigators noted reductions in serum retinol, RBP, and delayed dark adaptation. 27 Subsequent investigations showed a high correlation between HPR-induced reductions in serum RBP-retinol levels and manifestation of delayed dark adaptation. 42,43 In the present study, we performed a comprehensive analysis of the HPR mechanism of action and its capacity to reduce the accumulation of A2E-based lipofuscin fluorophores.…”

Section: Hpr Mechanism Of Action and Therapeutic Approachmentioning

confidence: 99%

Reductions in Serum Vitamin A Arrest Accumulation of Toxic Retinal Fluorophores: A Potential Therapy for Treatment of Lipofuscin-Based Retinal Diseases

Radu

Han

Bui

et al. 2005

Invest. Ophthalmol. Vis. Sci.

208

169

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Section: Hpr Mechanism Of Action and Therapeutic Approachmentioning

confidence: 99%

Reductions in Serum Vitamin A Arrest Accumulation of Toxic Retinal Fluorophores: A Potential Therapy for Treatment of Lipofuscin-Based Retinal Diseases

Radu

Han

Bui

et al. 2005

Invest. Ophthalmol. Vis. Sci.

208

169

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“…Along with lowering serum vitamin A, Fenretinide causes a dose-dependent reduction in rod function as measured by ERG [4][5][6][7] and dark-adaptometry [8,9]. At low doses, these visual effects were mild, and in prior studies with high doses (all in adults), the loss of rod function was never complete and it returned when the drug was stopped.…”

Section: Introductionmentioning

confidence: 99%

Total rod ERG suppression with high dose compassionate Fenretinide usage

2008

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Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.

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“…115 In addition, as a traditional drug for systemic use, fenretinide is thought to have less teratogenicity than isotretinoin 3,110 and exhibits no clinical signs of systematic vitamin A loss except for a delayed dark adaptability. 116,117 Retinylamine, also known as Ret-NH 2 , is a positively charged primary amine-containing retinoid. It has the ability to inhibit chromophore regeneration and rod function recovery, 12 probably by suppression of the RPE65-mediated isomerization process or blockage of retinal-derived by-product accumulation by directly binding excess free ATRal.…”

Section: Chemically Synthesized Regulators Of the Retinoid Metabolismmentioning

confidence: 99%

Potential Therapeutic Agents Against Retinal Diseases Caused by Aberrant Metabolism of Retinoids

Liu

Chen

Liu

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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The retinoid (visual) cycle is a complex enzymatic pathway that operates in the retina for the regeneration of 11-cis-retinal (11-cis-Ral), the inherent visual chromophore indispensable for vision. Deficiencies in the retinoid metabolism are involved in pathologic mechanisms of several forms of retinal diseases including age-related macular degeneration, Stargardt's disease, and Leber's congenital amaurosis, for which no effective cures presently exist. Nevertheless, the interference of abnormal retinoid metabolism with chemicals has been considered to be a promising strategy aimed at alleviating these retinal dysfunctions. Moreover, since gene therapy is gaining increasing importance in clinical practice, the modulation of key enzymes implicated with the retinoid cycle at a genetic level will hold great promise for the treatment of patients with degenerative diseases of the retina.

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Long-term effects of fenretinide on retinal function

Cited by 27 publications

References 19 publications

Reductions in Serum Vitamin A Arrest Accumulation of Toxic Retinal Fluorophores: A Potential Therapy for Treatment of Lipofuscin-Based Retinal Diseases

Reductions in Serum Vitamin A Arrest Accumulation of Toxic Retinal Fluorophores: A Potential Therapy for Treatment of Lipofuscin-Based Retinal Diseases

Total rod ERG suppression with high dose compassionate Fenretinide usage

Potential Therapeutic Agents Against Retinal Diseases Caused by Aberrant Metabolism of Retinoids

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