Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: A potential therapy for treatment of lipofuscin-based retinal diseases

Investigative Ophthalmology and Visual Science

Volumn 46, Issue 12, 2005, Pages 4393-4401

  Radu, Roxana A ^a   Han, Yun ^b   Bui, Tam V ^b   Nusinowitz, Steven ^a   Bok, Dean ^a,c   Lichter, Jay ^b   Widder, Ken ^b   Travis, Gabriel H ^a,c   Mata, Nathan L ^a,b  

^a JULES STEIN EYE INSTITUTE   (United States)

^b Sytera Inc   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FENRETINIDE; LIPOFUSCIN; RETINOL; RETINOL BINDING PROTEIN; A2E COMPOUND; ABC TRANSPORTER; ABCA4 PROTEIN, MOUSE; PREALBUMIN; PYRIDINIUM DERIVATIVE; RETINOID;

ABCA4 GENE; ADOLESCENT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOFLUORESCENCE; CELL STRUCTURE; CHROMATOPHORE; CONTROLLED STUDY; DARK ADAPTATION; DOSE RESPONSE; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG STRUCTURE; GEL PERMEATION CHROMATOGRAPHY; GENE; HISTOLOGY; LIPOFUSCINOSIS; MOUSE; NONHUMAN; PHOTORECEPTOR; PHOTOSENSITIVITY; PIGMENT EPITHELIUM; PRIORITY JOURNAL; RETINA DISEASE; SPECTROFLUOROMETRY; ANIMAL; BAGG ALBINO MOUSE; BLOOD; DRUG EFFECT; ELECTRORETINOGRAPHY; FLUORESCENCE MICROSCOPY; GEL CHROMATOGRAPHY; GENETICS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; METABOLISM; MOUSE MUTANT; PATHOLOGY; PHOTOSTIMULATION; RETINA; RETINA DEGENERATION;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DARK ADAPTATION; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRORETINOGRAPHY; FENRETINIDE; LIPOFUSCIN; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; MICROSCOPY, FLUORESCENCE; PHOTIC STIMULATION; PIGMENT EPITHELIUM OF EYE; PREALBUMIN; PYRIDINIUM COMPOUNDS; RETINA; RETINAL DEGENERATION; RETINOIDS; RETINOL-BINDING PROTEINS; SPECTROMETRY, FLUORESCENCE; VITAMIN A;

EID: 33644795859     PISSN: 01460404     EISSN: None     Source Type: Journal    
DOI: 10.1167/iovs.05-0820     Document Type: Article

References (49)

1. Klevering BJ, Deutman AF, Maugeri A, Cremers FP, Hoyng CB. The spectrum of retinal phenotypes caused by mutations in the ABCA4 gene. Graefes Arch Clin Exp Ophthalmol. 2005;243:90-100.
2. Zack DJ, Dean M, Molday RS, et al. What can we learn about age-related macular degeneration from other retinal diseases? Mol Vis. 1999;5:30-36.
3. von Ruckmann A, Schmidt KG, Fitzke FW, Bird AC, Jacobi KW. Fundus autofluorescence in patients with hereditary macular dystrophies, malattia leventinese, familial dominant and aged-related drusen [in German]. Klin Monatsbl Augenheilkd. 1998;213:81-86.
4. Steinberg RH. Interactions between the retinal pigment epithelium and the neural retina. Doc Ophthalmol. 1985;60:327-346.
5. Bok D. The retinal pigment epithelium: a versatile partner in vision. J Cell Sci Suppl. 1993;17:189-195.
6. Thompson DA, Gal A. Vitamin A metabolism in the retinal pigment epithelium: genes, mutations, and diseases. Prog Retin Eye Res. 2003;22:683-703.
7. Eldred GE, Lasky MR. Retinal age pigments generated by self-assembling lysosomotropic detergents. Nature. 1993;361:724-726.
8. Mata NL, Weng J, Travis GH. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci USA. 2000;97:7154-7159.
9. Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell. 1999;98:13-23.
10. Mata NL, Tzekov RT, Liu XR, Weng J, Birch DG, Travis GH. Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications for involvement of ABCR in age-related macular degeneration. Invest Ophthalmol Visual Sci. 2001;42:1685-1690.
11. Karan G, Lillo C, Yang Z, et al. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration. Proc Natl Acad Sci USA. 2005;102:4164-4169.
12. Ambati J, Anand A, Fernandez S, et al. An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med. 2003;9:1390-1397.
13. Holz FG, Bellman C, Staudt S, Schutt F, Volcker HE. Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42:1051-1056.
14. Spaide RF. Fundus autofluorescence and age-related macular degeneration. Ophthalmology. 2003;110:392-399.
15. Cideciyan AV, Aleman TS, Swider M, et al. Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum Mol Genet. 2004;13:525-534.
16. Schmitz-Valckenberg S, Bultmann S, Dreyhaupt J, Bindewald A, Holz FG, Rohrschneider K. Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2004;45:4470-4476.
17. Einbock W, Moessner A, Schnurrbusch UE, Holz FG, Wolf S; for the FAM Study Group. Changes in fundus autofluorescence in patients with age-related maculopathy. Correlation to visual function: a prospective study. Graefes Arch Clin Exp Ophthalmol. 2005;243:300-305.
18. Bergmann M, Schutt F, Holz FG, Kopitz J. Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2-E may contribute to the pathogenesis of age-related macular degeneration. FASEB J. 2004;18:562-564.
19. Sparrow JR, Vollmer-Snarr HR, Zhou J, et al. A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation. J Biol Chem. 2003;278:18207-18213.
20. De S, Sakmar TP. Interaction of A2E with model membranes. Implications to the pathogenesis of age-related macular degeneration. J Gen Physiol. 2002;120:147-157.
21. Katz ML, Drea CM, Robison WG Jr. Relationship between dietary retinol and lipofuscin in the retinal pigment epithelium. Mech Age Dev. 1986;35:291-305.
22. Katz ML, Eldred GE, Robison WG Jr. Lipofuscin autofluorescence: evidence for vitamin A involvement in the retina. Mech Age Dev. 1987;39:81-90.
23. Katz ML, Norberg M. Influence of dietary vitamin A on autofluorescence of leupeptin induced inclusions in the retinal pigment epithelium. Exp Eye Res. 1992;54:239-246.
24. Formelli F, Carsana R, Costa A, et al. Plasma retinol level reduction by the synthetic retinoid fenretinide: a one year follow-up study of breast cancer patients. Cancer Res. 1989;49:6l49-6l52.
25. Formelli F, Clerici M, Campa T, et al. Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations. J Clin Onc. 1993;11:2036-2042.
26. Conley B, O'Shaughnessy J, Prindiville S, et al. Pilot trial of the safety, tolerability, and retinoid levels of N-(4-hydroxyphenyl) retinamide in combination with tamoxifen in patients at high risk for developing invasive breast cancer. J Clin Onc. 2000;18:275-283.
27. Decensi A, Fontana V, Fioretto M, et al. Long-term effects of fenretinide on retinal function. Eur J Cancer. 1997;33:80-84.
28. Naik HR, Kalemkerian G, Pienta KJ. 4-Hydroxyphenylretinamide in the chemoprevention of cancer. Adv Pharmacol. 1995;33:315-347.
29. Berni R, Formelli F. In vitro interaction of fenretinide with plasma retinol-binding protein and its functional consequences. FEBS Lett. 1992;308:43-45.
30. Noy N, Xu ZJ. Interactions of retinol with binding proteins: implications for the mechanism of uptake by cells. Biochemistry. 1990;29:3878-3883.
31. Vogel S, Piantedosi R, O'Byrne SM, et al. Retinol-binding protein-deficient mice: biochemical basis for impaired vision. Biochemistry. 2002;41:15360-15368.
32. Nusinowitz S, Ridder W, Heckenlively JR. Electrodiagnostic techniques for visual function testing in mice. In: Smith RS, John SWM, Nishina PM, Sundberg JP, eds. Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods. Boca Raton, FL: CRC Press; 2002:320-344.
33. Nusinowitz S, Nguyen L, Radu R, Farber D, Danciger M. Electroretinographic evidence for reduced phototransduction gain and slowed photoreceptor recovery in albino mice with a MET450 variant in RPE65. Exp Eye Res. 2003;77:627-638.
34. Lamb TD, Pugh EN Jr. A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol. 1992;449:719-758.
35. Hood DC, Birch DG. Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity. Vision Res. 1993;33:1605-1618.
36. Hood DC, Birch DG. The a-wave of the human ERG and rod receptor function. Invest Ophthalmol Vis Sci. 1990;31:2070-2081.
37. Malpeli G, Folli C, Berni R. Retinoid binding to retinol-binding protein and the interference with the interaction with transthyretin. Biochim Biophys Acta. 1996;1294:48-54.
38. Holven KB, Natarajan V, Gundersen TE, Moskaug JO, Norum KR, Blomhoff R. Secretion of N-(4-hydroxyphenyl) retinamide-retinol-binding protein from liver parenchymal cells: evidence for reduced affinity of the complex for transthyretin. Int J Cancer. 1997;71:654-659.
39. Sabichi AL, Modiano MR, Lee JJ, et al. Breast tissue accumulation of retinamides in a randomized short-term study of fenretinide. Clin Cancer Res. 2003;9:2400-2405.
40. Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving PA, Travis GH. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Proc Natl Acad Sci USA. 2003;100:4742-4747.
41. Radu RA, Mata NL, Bagla A, Travis GH. Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt's macular degeneration. Proc Natl Acad Sci USA. 2004;101:5928-5933.
42. Caruso RC, Zujewski J, Iwata F, et al. Effects of fenretinide (4-HPR) on dark adaptation. Arch Ophthalmol. 1998;116:759-763.
43. Mariani L, Formelli F, De Palo G, et al. Chemoprevention of breast cancer with fenretinide (4-HPR): study of long-term visual and ophthalmologic tolerability. Tumori. 1996;82:444-4449.
44. Haralampus-Grynaviski NM, Lamb LE, Clancy CM, et al. Spectroscopic and morphological studies of human retinal lipofuscin granules. Proc Natl Acad Sci USA. 2003;100:3179-3184.
45. Marmorstein AD, Marmorstein LY, Sakaguchi H, Hollyfield JG. Spectral profiling of autofluorescence associated with lipofuscin, Bruch's membrane, and sub-RPE deposits in normal and AMD eyes. Invest Ophthalmol Vis Sci. 2002;43:2435-2441.
46. Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995;36:718-729.
47. Delori FC. Autofluorescence method to measure macular pigment optical densities fluorometry and autofluorescence imaging. Arch Biochem Biophys. 2004;430:156-162.
48. Katz ML, Wendt KD, Sanders DN. RPE65 gene mutation prevents development of autofluorescence in retinal pigment epithelial phagosomes. Mech Ageing Dev. 2005;126:513-521.
49. Hultin TA, McCormick DL, May CM, Moon RC. Effects of pretreatment with the retinoid N-(4-hydroxyphenyl)-all-trans-retinamide and phenobarbital on the disposition and metabolism of N-(4-hydroxyphenyl)-all-trans-retinamide in mice. Drug Metab Dispos. 1988;16:783-788.