The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration (original) (raw)

Abstract

One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch’s membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990’s, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye’s response to the dimerization products may dictate the retina’s lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

Similar content being viewed by others

References

• Bhosale P, Serban B, Bernstein PS (2009) Retinal carotenoids can attenuate formation of A2E in the retinal pigment epithelium. Arch Biochem Biophys 483:175–181
  Article CAS PubMed PubMed Central Google Scholar
• Brogan AP, Dickerson TJ, Boldt GE et al (2005) Altered retinoid homeostasis catalyzed by a nicotine metabolite: implications in macular degeneration and normal development. Proc Natl Acad Sci U S A 102:10433–10438
  Article CAS PubMed PubMed Central Google Scholar
• Charbel Issa P, Barnard A, Herrmann P et al (2015) Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization. Proc Natl Acad Sci doi: 10.1073/pnas.1506960112
  Google Scholar
• Dontsov AE, Koromyslova AD, Sakina NL (2013) Lipofuscin component A2E does not reduce antioxidant activity of DOPA-melanin. Bull Exp Biol Med 154:624–627
  Article CAS PubMed Google Scholar
• Eldred GE (1993) Retinoid reaction products in age related retinal degeneration. In: Hollyfield JG, Anderson RE, LaVail MM (eds) Retinal degeneration: clinical and laboratory applications. Plenum, New York, pp 15–24
  Chapter Google Scholar
• Finnemann S, Leung LW, Rodriguez-Boulan E (2002) The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium. Proc Natl Acad Sci U S A 99:3842–3847
  Article CAS PubMed PubMed Central Google Scholar
• Fishkin N, Jang YP, Itagaki Y et al (2003) A2-rhodopsin: a new fluorophore isolated from photoreceptor outer segments. Org Biomol Chem 1:1101–1105
  Article CAS PubMed Google Scholar
• Iriyama A, Fujiki R, Inoue Y et al (2008) A2E, a pigment of the lipofuscin of retinal pigment epithelial cells, is an endogenous ligand for retinoic acid receptor. J Biol Chem 283:11947–11953
  Article CAS PubMed Google Scholar
• Kaufman Y, Ma L, Washington I (2011) Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents. J Biol Chem 286:7958–7965
  Article CAS PubMed PubMed Central Google Scholar
• Lukiw WJ, Mukherjee PK, Cui JG et al (2006) A2E selectively induces cox-2 in ARPE-19 and human neural cells. Curr Eye Res 31:259–263
  Article CAS PubMed Google Scholar
• Ma L, Kaufman Y, Zhang J et al (2011) C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. J Biol Chem 286:7966–7974
  Article CAS PubMed PubMed Central Google Scholar
• Maeda A, Maeda T, Golczak M et al (2009) Involvement of all-trans-retinal in acute light-induced retinopathy of mice. J Biol Chem 284:15173–15183
  Article CAS PubMed PubMed Central Google Scholar
• Mihai DM, Washington I (2014) Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells. Cell Death Dis 5:e1348
  Article CAS PubMed PubMed Central Google Scholar
• Moiseyev G, Nikolaeva O, Chen Y et al (2010) Inhibition of the visual cycle by A2E through direct interaction with RPE65 and implications in Stargardt disease. Proc Natl Acad Sci U S A 107:17551–17556
  Article CAS PubMed PubMed Central Google Scholar
• Murdaugh LS, Wang Z, Del Priore LV et al (2010) Age-related accumulation of 3-nitrotyrosine and nitro-A2E in human Bruch’s membrane. Exp Eye Res 90:564–571
  Article CAS PubMed Google Scholar
• Penn J, Mihai DM, Washington I (2014) Morphologic and physiologic retinal degeneration induced by intravenous delivery of vitamin A dimers in the leporid retina. Dis Model Mech 8:131–8
  Google Scholar
• Radu RA, Hu J, Jiang Z et al (2014) Bisretinoid-mediated complement activation on retinal pigment epithelial cells is dependent on complement factor H haplotype. J Biol Chem 289:9113–9120
  Article CAS PubMed PubMed Central Google Scholar
• Sparrow JR, Boulton M (2005) RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 80:595–606
  Article CAS PubMed Google Scholar
• Sparrow JR, Gregory-Roberts E, Yamamoto K et al (2012) The bisretinoids of retinal pigment epithelium. Prog Retin Eye Res 31:121–135
  Article CAS PubMed PubMed Central Google Scholar
• Sparrow JR, Fishkin N, Zhou J et al (2003) A2E, a byproduct of the visual cycle. Vision Res 43:2983–2990
  Article CAS PubMed Google Scholar
• Thao MT, Renfus DJ, Dillon J et al (2014) A2E-mediated photochemical modification to fibronectin and its implications to age-related changes in Bruch’s membrane. Photochem Photobiol 90:329–334
  Article CAS PubMed Google Scholar
• Washington I, Jockusch S, Itagaki Y et al (2005) Superoxidation of bisretinoids. Angew Chem Int Ed Engl 44:7097–7100
  Article CAS PubMed Google Scholar
• Washington I, Turro NJ, Nakanishi K (2006) Superoxidation of retinoic acid. Photochem Photobiol 82:1394–1397
  CAS PubMed Google Scholar
• Yoon KD, Yamamoto K, Ueda K et al (2012) A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration. PLoS One 7:e41309
  Article CAS PubMed PubMed Central Google Scholar
• Zhou J, Jang YP, Kim SR et al (2006) Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci 103:16182–7
  Google Scholar

Download references

Acknowledgements

We thank the U.S. National Institutes of Health (1R01EY021207 and 5P30EY019007) and Research to Prevent Blindness (RPB) Inc., New York.

Author information

Authors and Affiliations

1. Department of Ophthalmology, Columbia University Medical Center, 160 Fort Washington Ave, Eye Research, 10032, New York, NY, USA
   Ilyas Washington
2. Alkeus Pharmaceuticals, Inc., 02210, Boston, MA, USA
   Leonide Saad

Authors

1. Ilyas Washington
   You can also search for this author inPubMed Google Scholar
2. Leonide Saad
   You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toIlyas Washington .

Editor information

Editors and Affiliations

1. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA
   Catherine Bowes Rickman
2. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA
   Matthew M. LaVail
3. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
   Robert E. Anderson
4. University Hospital Zurich, Zurich, Switzerland
   Christian Grimm
5. Case Western Reserve University Cleveland Clinic Lerner College of Med, Cleveland, Ohio, USA
   Joe Hollyfield
6. Univ of Florida Dept of Ophthalmology/Arb R112, Gainesville, Florida, USA
   John Ash

Rights and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this paper

Cite this paper

Washington, I., Saad, L. (2016). The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration. In: Bowes Rickman, C., LaVail, M., Anderson, R., Grimm, C., Hollyfield, J., Ash, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 854. Springer, Cham. https://doi.org/10.1007/978-3-319-17121-0\_46

Download citation

• .RIS
• .ENW
• .BIB
• DOI: https://doi.org/10.1007/978-3-319-17121-0\_46
• Published: 02 October 2015
• Publisher Name: Springer, Cham
• Print ISBN: 978-3-319-17120-3
• Online ISBN: 978-3-319-17121-0
• eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

Publish with us