- Anthony Donn Professor of Ophthalmic Sciences (in Ophthalmology)
- Professor of Pathology & Cell Biology
Vitamin A aldehyde-conjugates accumulate as lipofuscin in retinal pigment epithelial (RPE) cells and have been linked to disease processes in some inherited forms of macular degeneration as well as age-related macular degeneration. These bisretinoid constituents of lipofuscin are unique to RPE and in addition to A2E include all-trans-retinal dimer and its conjugates, phosphatidyl-dihydropyridine bisretinoid (A2-DHP-PE) and a conjugate of all-trans-retinal and glycerophosphoethanolamine (A2-GPE). The excitation and emission spectra of these compounds can also account for the inherent autofluorescence of the retina (fundus autofluorescence).
Dr. Sparrow’s laboratory has shown that the adverse effects of RPE lipofuscin pigments are attributable, at least in part, to their detergent-like structure and their photo-sensitive properties. In the latter case, bisretinoids can generate reactive forms of oxygen; they also undergo photooxidation and photodegradation. The photo-cleavage products of A2E consists of a complex mixture of aldehyde-bearing fragments that includes the small dicarbonyls methylglyoxal and glyoxal that are responsible for damaging modifications of proteins – advanced glycation end-products (AGEs). AGE-modified proteins are present in drusen. We are applying our understanding of RPE bisretinoids to clinical interpretations and measurements of fundus autofluorescence. Taken together work in the laboratory contributes to the elucidation of pathology in several retinal disorders including recessive Stargardt disease, retinitis pigmentosa, pattern dystrophies and age-related macular degeneration.
Therapeutic strategies her laboratory investigates to target bisretinoids include antioxidants, inhibitors of complement activation, small molecules that inhibit their formation and gene-based therapy.
Edward S. Harkness Eye Institute Research Annex160 Fort Washington Avenue
7th Floor, Room 701
New York, NY 10032
- (212) 305-9944
- (212) 305-9638
Honors & Awards
- Province of Ontario Graduate Scholarship
- Collip Medal, University of Western Ontario
- National Multiple Sclerosis Society Postdoctoral Fellowship
- National Institutes of Health Postdoctoral Fellowship
- Lew R. Wasserman Merit Award, Research to Prevent Blindness
- Alcon Research Institute Award
- Research to Prevent Blindness Senior Scientific Investigator Award
- Understanding the composition of RPE bisretinoid lipofuscin and conditions modulating its formation
- Investigating links between RPE lipofuscin and drusen formation in age-related macular degeneration
- Development of therapies to limit RPE lipofuscin formation
- Interpretation of patterns of fundus autofluorescence in retinal disorders
- Quantitation of fundus autofluorescence intensities
QUANTITATIVE FUNDUS AUTOFLUORESCENCE (P&S Industry Clinical Trial)
May 29 2017 - May 29 2022
QUANTITATIVE FUNDUS AUTOFLUORESCENCE IN RETINAL DISORDERS (Federal Gov)
Jun 1 2014 - May 31 2018
IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLS (Federal Gov)
May 1 2000 - Aug 31 2017
THERAPEUTIC APPROACHES FOR ABCA4-ASSOCIATED DISORDERS (Federal Gov)
Aug 1 2011 - Jul 31 2017
RETINAL MECHANISMS (Federal Gov)
Apr 1 2012 - Mar 31 2016
HUTC IN THE ROLE OF RPE LIPOFUSCIN, AND A2E COMPLEMENT DYSREGULATION IN AGE-RELATED MACULAR DEGENERATION (Private)
Mar 21 2013 - Sep 30 2014
FUNCTIONAL ANALYSES OF EMBRYONIC STEM CELL DERIVED RETINAL CELLS (NY State Gov)
Sep 1 2010 - Aug 31 2014
QUANTITATIVE FUNDUS AUTOFLUORESCENCE AND CORRELATIONS WITH GENOTYPE IN AGE RELATED MACULAR DEGENERATION (Private)
Jul 1 2013 - Jun 30 2014
LIMITING RPE LIPOSUSCIN ACCUMULATION BY HARNESSING ENZYME MEDIATED DEGRADATION (Private)
Dec 15 2009 - Sep 30 2013
TESTING VARIOUS CHROMOPHORES FOR USE IN IOLS: PROTECTION AGA INST 430 NM DAMAGE TO RPE CELLS THAT HAV (Private)
Apr 1 2010 - Mar 31 2012
RETINAL MECHANISMS AND VISUAL RESOLUTION (SUBCONTRACT WITH THE UNIVERISITY OF ROCHESTER) (Federal Gov)
Jan 1 2009 - Dec 31 2011
EFFICACY OF FACTOR H PREPARATIONS (Private)
Jan 17 2011 - Dec 14 2011
TOWARDS THERAPEUTIC DISCOVERY FOR MACULAR DEGENERATION (Private)
Dec 1 2010 - Aug 31 2011
INVESTIGATING INHIBITORS OF RPE LIPOFUSCIN FORMATION (Private)
Dec 1 2006 - Dec 31 2010
- Jilin Zhou, MD, Associate Research Scientist
- Keiko Ueda, PhD, Postdoctoral Research Scientist
- Zhao Llu, PhD, Postdoctoral Research Scientist
- Heike Schoenherr, PhD, Postdoctoral Research Scientist
- Erin Flynn, BS
- Janice David
Duncker T, Tabacaru MR, Lee W, Tsang SH, Sparrow JR, Greenstein VC. 2013. Comparison of near-infrared and short-wavelength autofluorescence in retinitis pigmentosa. Invest Ophthalmol Vis Sci 17:585-591.
Dobri N, Quin Q, Kong J, Yamamoto K, Liu Z, Moiseyev G, Ma JX, Allikmets R, Sparrow JR, Petrukhin K. 2013. A1120, a non-retinoid RBP4 antagonist inhibits formation of cytotoxic bisretinoids in an animal model of enhanced retinal lipofuscinogenesis. Invest Ophthalmol 7:85-95.
Gelman R, Chen R, Blonska A, Barile G, Sparrow JR. 2012. Fundus autofluorescence imaging in a patient with rapidly developing scotoma. Retinal Cases & Brief Reports 6:345-348.
Sparrow JR, Gregory-Roberts E, Yamamoto K, Blonska A, Ghosh SK, Ueda K, Zhou J. 2012. The bisretinoids of retinal pigment epithelium. Prog Retin Eye Res 31:121-135.
Yamamoto K, Zhou J, Hunter JJ, Williams DR, Sparrow JR. 2012. Toward an understanding of bisretinoid autofluorescence bleaching and recovery. Invest Ophthalmol Vis Sci 53:3536-3544.
Delori F. Greenberg JP, Woods RL, Fischer J, Bruncker T, Sparrow JR, Smith RT. 2012. Quantitative measurements of autofluorescence with the scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci 52:9379-9390.
Wu Y, Zhou J, Fishkin N, Rittman B.E. Sparrow JR. 2011. Enzymatic degradation of A2E, an RPE lipofuscin bisretinoid. Journal American Chemical Society 133:849-857.
Yamamoto K, Yoon KD, Ueda K, Hashimoto M, Sparrow JR. 2011. A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine. Invest Ophthalmol Vis Sci 52:9084-9090.
Wu Y, Yanase E, Feng X, Siegel MM, Sparrow JR. 2010. Structural characterization of bisretinoid A2E photocleavage products and implications for age-related macular degeneration. Proc Natl Acad Sci 107:7275-7280.
Sparrow JR, Yoon K, Wu Y, Yamamoto K. 2010. Interpretations of fundus autofluorescence from studies of the bisretinoids of retina. Invest Ophthalmol Vis Sci 51:4351-4357 (by invitation).
Chrispell JD, Feathers KL, Kane MA, Kim CY, Brooks M, Khanna R, Kurth I, Huebner CA, Gal A, Mears AJ, Swaroop A, Napoli JL, Sparrow JR, Thompson DA. RDH12. 2009. Activity and Effects on Retinoid Processing in the Murine Retina. J Biol Chem 284: 21468-21477.
Wu Y, Fishkin NE, Pande A, Pande J and Sparrow JR. 2009. A novel lipofuscin bisretinoid prominent in human retina and in a model of recessive Stargardt disease. J Biol Chem J Biol Chem 284:21468-21477
Ng KP, Gugiu BG, Renganathan K, Davies MW, Gu X, Crabb JS, Kim SR, Rozanowska MB, Bonilha VL, Rayborn ME, Salomon RG, Sparrow JR, Boulton ME, Hollyfield JG, Crabb JW. 2008. Retinal pigment epithelium lipofuscin proteomics. Mol Cell Proteomics. 7:1397-1405.
Kong J, Kim SR, Binley K, Pata I, Doi K, Mannik J, Zernant-Rajang J, Kan O, Iqball S, Naylor S, Sparrow JR, Gouras P, Allikmets R. 2008. Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy. Gene Therapy 15:1311-1320.
Kim SR, Jang YP, Jockusch S, Fishkin NE, Turro NJ, Sparrow JR. 2007. The all-trans-retinal dimer-series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model. Proc Natl Acad Sci U S A 104:19273-19278.
Zhou J, Jang YP, Kim SR, Sparrow JR. 2006. Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci 103:16182-16187.
Maiti, P, Kong J, Kim SR, Sparrow JR, Alllikmets R and Rando RR. 2006. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry 45:852-860