Janet R. Sparrow, PhD
- Anthony Donn Professor of Ophthalmic Sciences (in Ophthalmology)
- Professor of Pathology & Cell Biology
Work in the laboratory is aimed at examining a causal link between the intracellular accumulation of lipofuscin fluorophores and retinal pigmented epithelial (RPE) cell death. We have shown that a major fluorophore of RPE lipofuscin, A2E, confers a susceptibilty to blue light-mediated cell death and can lead to a detergent-like perturbation of membranes. We are also examining mechanisms involved in A2E biosynthesis and conditions under which the formation of A2E may be accelerated. The death of RPE cells in several retinal disorders including Stargardt's disease and atrophic age-related macular degeneration (AMD), precedes the degeneration of photoreceptor cells and the impairment of vision. A major focus of work in the laboratory involves studies of a causal link between the intracellular accumulation of aging pigments (lipofuscin) in the RPE and the death of those cells. A major hydrophobic constituent of RPE lipofuscin is the fluorophore A2E, a bis-retinoid whose biosynthesis begins randomly in photoreceptor cell outer segments. A2E is generated from the precursor A2-PE after phosphate hydrolysis, it is deposited in RPE cells secondary to phagocytosis of shed outer segment membrane and it accumulates as lipofuscin because it cannot be degraded by RPE lysosomal enzymes. Light is also involved in mechanisms that lead to the atrophy of A2E-laden RPE. Thus, accumulation of A2E in the lysosomal compartment of the cultured RPE confers a susceptibilty to blue light-mediated cell death; the wavelength dependency of this effect is consistent with the excitation spectra of A2E and with the known susceptibility of RPE cells to blue light damage in animal models. The cell death program which is initiated by blue light illumination of A2E involves the activation of caspase-3 a downstream cysteine-dependent protease and is regulated by Bcl-2 an anti-apoptotic protein situated in the outer mitochondrial membrane. Evidence indicates that the generation of singlet oxygen upon photoexcitation of A2E is integral to the death of the cells. In particular singlet oxygen which is generated by photosensitization of A2E becomes inserted into carbon-carbon double bonds of the retinoid-side arms of A2E to generate highly reactive epoxides. Since the considerable ring strain and electrophilicity of these three-membered oxygen and carbon containing rings makes them susceptible to reaction with nucleophilic macromolecules such as DNA and protein, A2E-epoxides may be agents that ravage the cell. Indeed, we have shown that at least one of the subcellular structures damaged by A2E-epoxides, is DNA with guanine bases of DNA being oxidatively modified to generate 8-oxo-dG and perhaps other structurally related lesions. In other experiments, A2E-epoxides have been shown to generate products of lipid peroxidation in RPE cells. The mediation of light damage may not be the only mechanism by which A2E induces cell injury, since A2E can also mediate a detergent-like perturbation of cell membranes. The structure of A2E, both its possession of hydrophobic and hydrophilic domains and its wedge-shaped configuration, is central to this property. These studies are relevant to the non-neovascular, atrophic form of age-related macular degeneration that accounts for up to 21% of the visual loss associated with AMD and that is characterized by a massive accumulation of lipofuscin preceding RPE cell death. These observations also revive the unresolved issue of whether lifelong exposure to bright light contributes to AMD.
Credentials & Experience
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
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.
- 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
RETINAL DISEASE PROMOTED BY IRON-INDUCED BISRETINOID OXIDATION (Federal Gov)
Apr 1 2018 - Jan 31 2023
QUANTITATIVE FUNDUS AUTOFLUORESCENCE (P&S Industry Clinical Trial)
May 29 2017 - May 29 2022
IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLS (Federal Gov)
Sep 30 2017 - Jun 30 2020
QUANTITATIVE FUNDUS AUTOFLUORESCENCE IN RETINAL DISORDERS (Federal Gov)
Jun 1 2014 - May 31 2019
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
- Duncker T, Lee W, Jiang F, Ramachandran R, Hood DC, Tsang SH, Sparrow JR, Greenstein VC. 2017. ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina. Retina. [Epub ahead of print] PMCID: PMC5522759
- Schuerch K, Woods RL, Lee W, Duncker T, Delori FC, Allikmets R, Tsang SH, Sparrow JR.2017. Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa. Invest Ophthalmol Vis Sci: 58(3):1843-1855. PMCID: PMC5377994
- Sparrow JR. 2017. Quantitative Fundus Autofluorescence. JAMA Ophthalmol 135(4):403.
- Zhao J, Kim HJ, Sparrow JR. 2017. Multimodal Fundus Imaging of Sodium Iodate-Treated Mice Informs RPE Susceptibility and Origins of Increased Fundus Autofluorescence. Invest Ophthalmol Vis Sci; 58(4):2152-2159. PMCID: PMC5389744
- Zernant J, Lee W, Collison FT, Fishman GA, Sergeev YV, Schuerch K, Sparrow JR, Tsang SH, Allikmets R. 2017.Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration. J Med Genet; 54(6):404-412. Epub 2017 Apr 26.
- Lee W, Schuerch K, Zernant J, Collison FT, Bearelly S, Fishman GA, Tsang SH, Sparrow JR, Allikmets R. 2017. Genotypic spectrum and phenotype correlations of ABCA4-associated disease in patients of south Asian descent. Eur J Hum Genet: 25(6):735-743. PMCID: PMC5477356
- Wang Y, Kim HJ, Sparrow JR. 2017. Quercetin and cyanidin-3-glucoside protect against photooxidation and photodegradation of A2E in retinal pigment epithelial cells. Exp Eye Res: 160:45-55. PMCID: PMC5556693
- Lee, W, Schürch K, Xie Y, Zernant J, Tsang ST, Sparrow JR, Allikmets R. 2016. Simultaneous expression of ABCA4 and GPR143 mutations: a complex phenotypic manifestation. Invest Ophthalmol Vis Sci: 57: 3409-3415. PMCID: PMC4961055
- Schuerch K, Marsiglia M, Lee W, Tsang SH, Sparrow JR. 2016. Multimodal imaging of disease-associated pigmentary changes in retinitis pigmentosa. Retina: 36 Suppl 1: S147-S158. PMCID: PMC5193227
- Ueda K, Zhao J, Kim HJ, Sparrow JR. 2016. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration. Proc Natl Acad Sci. 113: 6904-6909. PMCID: PMC4922174
- Zhou J, Ueda K, Zhao J, Sparrow JR. 2015. Correlations between photodegradation of bisretinoid constituents of retina and dicarbonyl-adduct deposition. J Biol Chem 290: 27215-27. PMCID: PMC4646369
- Duncker T, Stein GE, Lee W, Tsang SH, Zernant J, Bearelly S, Hood DC, Greenstein VC, Delori FC, Allikmets R, Sparrow JR. Quantitative fundus autofluorescence and optical coherence tomography in ABCA4 carriers. 2015. Invest Ophthalmol Vis Sci. 56:7274-7285. PMCID: PMC4642605
- Sparrow JR, Marsiglia M, Allikmets R, Tsang S, Lee W, Duncker T, Zernant J. 2015. Flecks in recessive Stargardt disease: short-wavelength autofluorescence, near-infrared autofluorescence and optical coherence tomography. Invest Ophthalmol Vis Sci 56:5029-5039. PMCID: PMC4525681.
- Liu Z, Ueda K, Kim HJ, Sparrow JR. 2015. Photobleaching and fluorescence recovery of RPE bisretinoids. PLOS ONE 10(9):e0138081. PMCID: PMC4569084
- Duncker T, Tsang SH, Woods RL, Lee W, Zernant J, Allikmets R, Delori FC, Sparrow JR. 2015. Quantitative fundus autofluorescence and optical coherence tomography in PRPH2/RDS- and ABCA4-associated disease exhibiting phenotypic overlap. Invest Ophthalmol Vis Sci 56:3159-3170. PMCID: PMC4451616.
- Greenstein VC, Schuman AD, Lee W, Duncker T, Zernant J, Allikmets R, Hood DC, Sparrow JR. 2015. Near-infrared autofluorescence: its relationship to short-wavelength autofluorescence and optical coherence tomography in recessive Stargardt disease. Invest Ophthalmol Vis Sci. 56:3226-3234. PMCID: PMC4453463.
- Marsiglia M, Lee W, Mahajan VB, Zernant J, Delori FC, Tsang SH, Sparrow JR. 2015. Quantitative autofluorescence as a clinical tool for expedited differential diagnosis of retinal degeneration. JAMA Ophthalmol 133: 219-20. PMCID: PMC4370211.
- Duncker T, Marsiglia M, Lee W, Zernant J, Tsang SH, Allikmets R, Greenstein VC, Sparrow JR. 2014. Correlations amongst near-infrared and short-wavelength autofluorescence and spectral domain optical coherence tomography in recessive Stargardt disease. Invest Ophthalmol Vis Sci 55:8134-8143.PMCID: PMC4266077
- Duncker T, Tsang SH, Lee W, Zernant J, Allikmets R, Delori FC, Sparrow JR. 2014. Quantitative fundus autofluorescence distinguishes ABCA4-associated and non-ABCA4-associated Bull’s Eye Maculopathy. Ophthalmology 122: 345-55. PMCID: PMC4306619
- Lee W, Noupuu K, Oll M, Duncker T, Burke TR, Zernant J, Bearelly S, Tsang SH, Sparrow JR, Allikmets R. 2014. The external limiting membrane in early-onset Stargardt disease. Invest Ophthalmol Vis Sci 55: 6139-49. PMCID: PMC4184384
- Flynn E, Ueda K, Auran E, Sullivan JM, Sparrow JR. 2014. Fundus autofluorescence and photoreceptor cell rosettes in mouse models. Invest Ophthalmol Vis Sci 55: 5643-5652. PMCID: PMC4161488
- Liu Z, Qin T, Zhou J, Taylor A, Sparrow JR, Shang F. 2014. Impairment of the Ubiquitin-Proteasome Pathway in RPE Alters the Expression of Inflammation Related Genes. Adv Exp Med Biol 801:237-50. PMCID: PMC4828937
- Sparrow JR, Zhou J, Ghosh SK, Liu Z. 2014. Bisretinoid degradation and the ubiquitin-proteasome system. Adv Exp Med Biol 801:593-600. PMCID: PMC4832918
- Burke TR, Duncker T, Woods RL, Greenberg JP, Zernant J, Tsang SH, Smith RT, Allikmets R, Sparrow JR, Delori FC. 2014. Quantitative Fundus Autofluorescence in Recessive Stargardt Disease. Invest Ophthalmol Vis Sci 55:2841-52. PMCID: PMC4008047
- Wu L, Ueda K, Nagasaki T, Sparrow JR. 2014. Light damage in Abca4 and Rpe65rd12 mice. Invest Ophthalmol 55:1910-1918. PMCID: PMC3973190
- Duncker T, Greenberg, JP, Ramachandran R, Hood DC, Smith RT, Hirose T, Woods RL, Tsang SH, Delori FC, Sparrow JR. 2014. Quantitative fundus autofluorescence and optical coherence tomography in Best Vitelliform Macular Dystrophy. Invest Ophthalmol Vis Sci 55: 1471-1482. PMCID: PMC3954365
- Yang J, Li Y, Chan L, Tsai Y-T, Hsuan, W, Nguyen, HV, Hsu, C-W, Li X, Brown LM, Egli, D. Sparrow JR, Tsang SH. 2014. Validation of GWAS alleles with patient-specific stem cell lines. Human Molecular Genetics 23: 3445-3455. PMCID: PMC4049304
- Park SP, Siringo FS, Pensec N, Hong IH, Sparrow J, Barile G, Tsang SH, Chang S. 2013. Comparison of fundus autofluorescence between fundus camera and confocal scanning laser ophthalmoscope-based systems. Ophthalmic Surg Lasers Imaging Retina 44:536-43. PMCID: PMC4405534
- Koirala A, Conley SM, Makkia R, Liu Z, Cooper MJ, Sparrow JR, Naash MI. 2013. Persistence of non-viral vector mediated RPE65 expression: Case for viability as a gene transfer therapy for RPE-based diseases. J Control Release 172:745-52. PMCID: PMC3858392
- Duncker T, Lee W, Tsang SH, Greenberg JP, Zernant J, Allikmets R, Sparrow JR. 2013. Distinct characteristics of inferonasal fundus autofluorescence patterns in Stargardt disease and retinitis pigmentosa. Invest Ophthalmol Vis Sci 54:6820-6. PMCID: PMC3799564
- Van der Burght BW, Hansen M, Olsen J, Zhou J, Wu Y, Nissen MH, Sparrow JR. 2013. Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells. Acta Ophthalmol 91:e537-45. PMCID: PMC4955808
- Greenberg JP, Duncker T, Woods RL, Smith RT, Sparrow JR, Delori FC. 2013. Quantitative fundus autofluorescence in healthy eyes. Invest Ophthalmol Vis Sci. 54:5684-5693. PMCID: PMC3759220
- Sparrow JR, Blonska A, Flynn E, Duncker T, Greenberg JP, Secondi R, Ueda K, Delori FC. 2013. Quantitative fundus autofluorescence in mice. Correlation with HPLC quantitation of RPE lipofuscin and measurement of retinal outer nuclear layer thickness. Invest Ophthalmol Vis Sci. 54:2812-2820. PMCID: PMC3632269
- Santos RA, Keegan DJ, Fuchs BS, Song BJ, Avila MP, Simpson N, Sparrow JR, Chang S. 2013. DFPE, partially fluorinated ether: a novel approach for experimental intravitreal tamponade. Retina 33:120-127.
- Joshi E, Field J, Murphy J, Abdelrahim, Schonherr H, Sparrow JR, Ellestad G, Hakanishi K, Zask A. 2013 Synthesis of antioxidants for prevention of age-related macular degeneration. J Nat Prod 76:450-454. PMCID:PMC4069254
- Dobri N, Qin 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 Vis Sci 54:85-95. PMCID:PMC3544424
- 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 54:585-591. PMCID:PMC3558299
- Duncker, T, Greenberg JP, Sparrow JR, Smith RT, Quigley HA, Delori FC. 2012. Visualization of the optic fissure in short-wavelength autofluorescence images of the fundus. Invest Ophthalmol Vis Sci 53:6682-6686. PMCID:PMC3462479
- 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. PMCID:PMC3535223
- Secondi R, Kong J, Blonska A, Staurenghi G, Sparrow JR. 2012. Fundus autofluorescence findings in a mouse model of retinal detachment. Invest Ophthalmol Vis Sci 53:5190-5197. PMCID:PMC3416030
- Yoon KD, Yamamoto K, Ueda K, Zhou J, Sparrow JR. 2012. A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration. PLoS One 7(7):e41309. PMCID:PMC3400616
- Bian Q, Gao S, Zhou J, Qin J, Taylor A, Johnson EJ, Tang G, Sparrow JR, Gierhart D, Shang F. 2012. Lutein and zeaxanthin supplementation reduces photo-oxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells. Free Radic Biol Med 53: 1298-307. PMCID:PM3744865
- 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. PMCID:PMC3231846
- 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. PMCID:PMC3250263
- 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. PMCID:PMC3231846
- Conley SM, Cai X, Makkia R, Wu Y, Sparrow JR, Naash MI. 2011. Increased cone sensitivity to ABCA4 deficiency provides insight into macular vision loss in Stargardt’s dystrophy. Biochim Biophys Acta 1822: 1169-1179. PMCID:PMC3351560
- Yoon KD, Yamamoto K, Zhou J, Sparrow JR. 2011. Photo-products of retinal pigment epithelial bisretinoids react with cellular thiols. Mol Vis 17:1839-1849. PMCID:PMC3137558
- Zhou J and Sparrow JR. 2011. Light filtering in a retinal pigment epithelial cell culture model. Optom Vis Sci 88:759-765. PMCID:PMC3100371
- 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. PMCID:PMC4112458
- Sparrow JR, Wu Y, Nagasai T, Yoon K, Yamamoto K, Zhou J. 2010. Fundus autofluorescence and the bisretinoids of retina. Photochem Photobiol Sci 9: 1480-1489. PMCID:PMC4071605
- 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. PMCID:PMC2867734
- Wu L, Nagasaki T and Sparrow JR. 2010. Photoreceptor cell degeneration in Abcr-/- mice. Adv Exp Med Biol 664:533-539. PMCID:PMC2914303
- Kuny S, Gaillard F, Mema S, Freund P, Zhang K, Macdonald IM, Sparrow JR, Sauve Y. 2010. Inner retina remoding in a mouse model of Stargardt-like macular dystrophy. Invest Ophthalmol Vis Sci 51:2248-2262. PMCID:PMC2868397
- Kim SR, Jang Y, Sparrow JR. 2010. Photooxidation of RPE lipofuscin bisretinoids enhances fluorescence intensity. Vision Res 50:729-736. PMCID:PMC2840058
- Vasireddy V, Jablonski MM, Khan NW, Wang XF, Sahu P, Sparrow JR, Ayyagari R. 2009. Elovl4 5-bp deletion knock-in mouse model for Stargardt-like macular degeneration demonstrates accumulation of ELOVL4 and lipofusin. Exp Eye Research 89:905-912. PMCID:PMC2783393
- 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. 2009. RDH12 activity and effects on retinoid processing in the murine retina. J Biol Chem 284: 21468-21477. PMCID:PMC2755871
- 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 284:21468-21477. PMCID:PMC2740442
- Damek-Poprawa M, Diemer T, Lopes VS, Lillo C, Harper DC, Marks MS, Wu Y, Sparrow JR, Rachel R, Willliams DS, Boesze-Battaglia K. 2009. Melanoregulin (MREG) modulates lysosome function in pigment epithelial cells. J Biol Chem 283:20745-20753. PMCID:PMC2667774
- Westlund BS, Cai B, Zhou J, Sparrow JR. 2009. The involvement of c-Abl, p53 and the MAP kinase JNK in the cell death program initiated in A2E-laden ARPE-19 cells by exposure to blue light. Apoptosis 14:31-41. PMCID:PMC3099593
- Zhou J, Kim SR, Westlund B, Sparrow JR. 2009. Complement activation by bisretinoid constituents of RPE lipofuscin. Invest Ophthalmol Vis Sci 50:1392-1399. PMCID:PMC2669319
- Lukinova N, Dentchev T, Iacovelli J, Amado D, Wolkow N, Ying GS, Sparrow JR, Dunaief, JL. 2009. Iron chelation protects the retinal pigment epithelial cell line ARPE-19 against cell death triggered by diverse stimuli. Invest Ophthalmol Vis Sci 50: 1440-1447. PMCID:PMC2665187
- Zhang X, Zhou J, Fernandes AF, Sparrow JR, Pereira P, Taylor A, Shang F. 2008. The proteasome is a target of oxidative damage in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 49(8):3622-3630. PMCID:PMC2694183
- 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. PMCID:PMC2493379
- Fernandes AF, Zhou J, Zhang X, Bian Q, Sparrow JR, Taylor A, Pereira P, Shang F. 2008. Oxidative inactivation of the proteasome in RPE: A potential link between oxidative stress and upregulation of IL-8. J Biol Chem. 283:20745-20753. PMCID: PMC2475710
- Kim SR, Jockusch S, Itagaki Y, Turro NJ, Sparrow JR. 2008. Mechanisms involved in A2E oxidation. Exp Eye Research 86:975-982. PMCID:PMC2474777
- 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. PMCID:PMC3110063
- Allocca M, Doria M, Petrillo M, Colella P, Garcia-Hoyos M, Gibbs D, Kim SR, Maguire A, Rex TS, Vicino, UD, Sparrow JR, Williams DS, Bennett J, Auricchio, A. 2008. Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective in vivo gene delivery in mice. J Clin Investigation 118: 1955-64. PMCID:PMC2298836
- Zhou J, Jang YP, Chang S, Sparrow JR. 2008. OT-674 suppresses photooxidative processes initiated by an RPE lipofuscin fluorophore. Photochem Photobiol. 84:75-80.
- Sparrow JR, Kim SR, Cuervo AM, Bandhyopadhyayand U. 2008. A2E, a pigment of RPE lipofuscin is generated from the precursor A2PE by a lysosomal enzyme activity. Adv Exp Med Biol. 613:393-398.
- 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 A104:19273-19278. PMCID:PMC2148280
- Abeywickrama C, Matsuda H, Jockusch S, Zhou J, Jang YP, Chen BX, Itagaki Y, Erlanger BF, Nakanishi K, Turro NJ, Sparrow JR. 2007. Immunochemical recognition of A2E, a pigment in the lipofuscin of retinal pigment epithelial cells. Proc Natl Acad Sci U S A. 104:14610-14611. PMCID:PMC1976245
- Kim SR, He J, Yanase E, Jang YP, Berova N, Sparrow JR, Nakanishi K. 2007. Characterization of dihydro-A2PE: an intermediate in the A2E biosynthetic pathway. Biochemistry 46: 10122-10129. PMCID:PMC2557066
- Verline J, Pang JJ, Kutralanathan R, Zhan X, Crabb JW, Kim SR, Sparrow JR, Hauswirth WW, Lewin AS. 2007. SOD2 knockdown mice model early AMD. Invest Ophthalmol Vis Sci. 48: 4407-4420.
- Washington I, Zhou J, Jockusch S, Turro NJ, Nakanishi K, Sparrow JR. 2007. Chlorophyll derivatives as visual pigments for super vision in the red. Photochem Photobiol Sci 6:775-779.
- Greenstein VC, Chiosi F, Baker P, Seiple W, Holopigian K, Braunstein RE, Sparrow JR. 2007. Scotopic sensitivity and color vision with a blue light-absorbing intraocular lens. J Cataract Refract Surg 33:667-672. PMCID:PMC1913934
- 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. PMCID:PMC1637557
- Turner B, Sparrow JR, Cai B, Monroe J, Mikawa T, Hempstead BL. 2006. TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decision. Developmental Biol. 29:455-465. PMCID:PMC2623246
- 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.
- Sparrow JR, Cai B, Jang YP, Zhou J, Nakanishi K. 2006. A2E, a fluorophore of RPE lipofuscin, can destabilize membrane. Adv Exp Med and Biol 572:63-68.
- Zhou J, Gao X, Cai B, Sparrow JR. Indirect antioxidant protection against photooxidative processes initiated in retinal pigment epithelial cells by a lipofuscin pigment. Rejuvenation Res. 9:256-263.
- Kim SR, Nakanishi K, Itagaki Y, Sparrow JR. 2006. Photooxidation of A2-PE, a photoreceptor outer segment fluorophores and protection by lutein and zeaxanthin. Exp Eye Research 82: 828-839.
- Jang YP, Matsuda H, Itagaki Y, Nakanishi K, Sparrow JR. 2005. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin. J Biol Chem 280:39732-39739.
- Smith RT, Koniarek JP, Chan J, Nagasaki T, Sparrow JR, Langton. 2005. Autofluorescence characteristics of normal foveas and reconstruction of foveal autofluorescence from limited data subsets. Invest Ophthalmol Vis Sci 46:2940-2946. PMCID:PMC2754769
- Fishkin N, Sparrow JR, Allikmets R, Nakanishi K. 2005. Isolation and characterization of a novel retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugate. Proc Natl Acad Sci 102:7091-7096. PMCID:PMC1129110
- Jang YP, Zhou J, Nakanishi K, Sparrow JR. 2005. Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cells. Photochem Photobiol 81:529-536. PMCID: PMC1351305
- Zhou J, Cai B, Jang YP, Pachydaki S, Schmidt AM, Sparrow JR. 2005. Mechanisms for the induction of HNE- MDA- and AGE-adducts, RAGE and VEGF in retinal pigment epithelial cells. Exp Eye Research 80:567-580.
- Smith RT, Chan JK, Nagasaki T, Ahmad UF, Barbazetto I, Sparrow JR, Figueroa M. Merriam J. 2005. Automated detection of macular drusen using geometric background leveling and threshold selection. Arch Ophthalmol 123:200-206. PMCID: PMC2884376
- Fishkin N, Pescitelli G, Sparrow JR, Berova N, Nakanishi K. 2004. Absolute configurational determination of an all-trans-retinal dimer isolated from photoreceptor outer segments. Chirality 16:637-641.
- Kim SR, Fishkin N, Kong J, Nakanishi K, Allikmets R, Sparrow JR. 2004. The Rpe65 Leu450Met variant is associated with reduced levels of the RPE lipofuscin fluorophores A2E and iso-A2E. Proc Natl Acad Sci 101:11668-11672. PMCID:PMC511036
- Smith RT, Chan JK, Nagasaki T, Sparrow JR, Barbazetto I. 2004. A method for drusen measurement based on reconstruction of fundus background reflectance. Br J Ophthalmol 89:87-91. PMCID:PMC1772480
- Jockusch S, Ren RX, Jang YP, Itagaki Y, Vollmer-Snarr H, Sparrow JR, Nakanishi K, Turro NJ. 2004. Photochemistry of A1E, a retinoid with a conjugated pyridinium moiety: competition between pericyclic photooxygenation and pericylization. J Am Chem Soc 126:4646-4652.
- Smith RT, Nagasaki T, Sparrow JR, Barbazetto I, Koniarek JP, Bickmann LJ. 2004. Photographic patterns in macular images: representation by a mathematical model. J Biomed Optics 9:162-172.
- Sparrow JR, Miller AS, Zhou J. 2004. A blue absorbing intraocular lens and RPE protection in vitro. J Cataract Refract Surg 30:873-878.
- Sparrow JR, Fishkin N, Zhou J, Cai B, Jang YP, Krane S, Itagaki Y, Nakanishi K. 2003. A2E, a byproduct of the visual cycle. Vision Research 43: 2983-2990.
- Ciardella AP, Schiff W, Barile G, Vidne O, Sparrow JR, Langton K, Chang S. 2003. Persistent indocyanine green fluorescence after vitrectomy for macular hole. Am J Ophthalmol 136:174-177.
- Smith RT, Nagasaki T, Sparrow JR, Barbazetto I, Klaver CW, Chan JK. 2003. A method of drusen measurement based on the geometry of fundus reflectance. BioMedical Engineering OnLine 2:10. PMCID: PMC155640
- Fishkin N, Jang YP, Itagaki Y, Sparrow JR, Nakanishi K. 2003. A2-rhodopsin: A new fluorophore isolated from photoreceptor outer segments. Organic and Biomolecular Chemistry 1:1101-1105.
- Sparrow JR, Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, Nakanishi K. 2003. A2E-epoxides damage DNA in retinal pigiment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation. J Biol Chem 278:18207-18213.
- Sparrow JR, Zhou J, Cai B. 2003. DNA is the target of the photodynamic effects elicited in A2E-laden RPE by blue light illumination. Invest Ophthalmol Vis Sci 44:2245-2251.
- Ben-Shabat S, Itagaki Y, Jockusch S, Sparrow JR, Turro NJ, Nakanishi K. 2002. Formation of a nona-oxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angewandte Chemie 41:814-817.
- Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K. 2002. Involvement of oxidative mechanisms in blue light-induced damage to A2E-laden RPE. Invest Ophthalmol Vis Sci 43:1222-1227.
- Ben-Shabat S, Parish CA, Vollmer HR, Itagaki Y, Fishkin N, Nakanishi K, Sparrow JR. 2002. Biosynthetic studies of A2E, a major fluorophore of RPE lipofuscin. J Biol Chem 277:7183-7190.
- Sparrow JR, Cai B. 2001. Blue light induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci 42:1356-1362.
- Kuang K, Li Y, Wen Q, Wang Z, Li J, Yang Y, Iserovich P, Reinach PS, Sparrow JR, Diecke FPJ, Fischbarg J. 2000. Corneal endothelial Na+-K+ -2Cl- cotransporter: molecular identification, location and contribution to fluid transport. Am J Physiol 280: C491-499.
- Liu J, Itagaki Y, Ben-Shabat S, Nakanishi K, Sparrow JR. 2000. The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane. J Biol Chem 275:29354-29360.
- Das I, Sparrow JR, Lin M, Shih E, Mikawa T, Hempstead BL. 2000. Trk C signaling is required for retinal progenitor cell proliferation. J Neurosci 20:2887-2895.
- Sparrow JR, Nakanishi K, Parish CA. 2000. The lipofuscin fluorophore A2E mediates blue-light induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 41:1981-1989.
- Canki M, Sparrow JR, Chao W, Potash MJ, Volsky DJ. 2000. Human immunodeficiency virus type I can infect human retinal pigment epithelial cells in culture and can impair their phagocytosis of rod outer segment membranes. Aids Research and Human Retroviruses 16:453-463.
- Sparrow JR, Parish CA, Nashimoto M, Nakanishi K. 1999. A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture. Invest Ophthalmol Vis Sci 40:2988-2995.