Research Topics
| J R SparrowSummaryAffiliation: Columbia University Country: USA Publications
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Publications
Complement dysregulation in AMD: RPE-Bruch's membrane-choroidJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Mol Aspects Med 33:436-45. 2012..One recurring theme is the potential for disease promotion by diverse types of oxidation products...
The bisretinoids of retinal pigment epitheliumJanet R Sparrow
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Prog Retin Eye Res 31:121-35. 2012..Accordingly, we will discuss recent findings that implicate the photodegradation of bisretinoid in the etiology of age-related macular degeneration...
A method of drusen measurement based on the geometry of fundus reflectanceR Theodore Smith
Department of Ophthalmology, Columbia University, New York, NY, USA
Biomed Eng Online 2:10. 2003..Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method...
Blue light-absorbing intraocular lens and retinal pigment epithelium protection in vitroJanet R Sparrow
Department of Ophthalmology, Columbia University, 630 West 128th Street, New York, NY 10032, USA
J Cataract Refract Surg 30:873-8. 2004....
A2E, a fluorophore of RPE lipofuscin: can it cause RPE degeneration?Janet R Sparrow
Department of Ophthalmology and Chemistry, Columbia University, New York, NY 10032, USA
Adv Exp Med Biol 533:205-11. 2003
RPE lipofuscin and its role in retinal pathobiologyJanet R Sparrow
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Exp Eye Res 80:595-606. 2005..Since recent findings with respect to the origin, composition and adverse effects of RPE lipofuscin have informed our view of this material, the goal of this article is to review our current understanding of these issues...
Phospholipid meets all-trans-retinal: the making of RPE bisretinoidsJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
J Lipid Res 51:247-61. 2010..The propensity of these compounds to negatively impact on the cells has been linked to the pathogenesis of some retinal disorders including juvenile onset recessive Stargardt disease and age-related macular degeneration...
A2E, a pigment of RPE lipofuscin, is generated from the precursor, A2PE by a lysosomal enzyme activityJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Adv Exp Med Biol 613:393-8. 2008
Bisretinoids of RPE lipofuscin: trigger for complement activation in age-related macular degenerationJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY, USA
Adv Exp Med Biol 703:63-74. 2010..As such, these photooxidative processes, in a setting of complement dysregulation could contribute to chronic inflammation underlying AMD pathogenesis...
Fundus autofluorescence and the bisretinoids of retinaJanet R Sparrow
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Photochem Photobiol Sci 9:1480-9. 2010..However, two retinoids of the visual cycle, all-trans-retinyl ester and all-trans-retinal, did not exhibit fluorescence at 488 nm excitation...
The retinal pigment epithelium in health and diseaseJ R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Curr Mol Med 10:802-23. 2010..The magnitude of the demands imposed on this single layer of cells in order to execute these tasks, will become apparent to the reader of this review as will the number of clinical disorders that take origin from these cells...
A2E, a byproduct of the visual cycleJanet R Sparrow
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Vision Res 43:2983-90. 2003....
Therapy for macular degeneration: insights from acneJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10028, USA
Proc Natl Acad Sci U S A 100:4353-4. 2003
Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPEJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Invest Ophthalmol Vis Sci 43:1222-7. 2002..The purpose of this study was to evaluate the role of oxidative mechanisms in mediating the cellular damage...
A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formationJanet R Sparrow
Department of Ophthalmology and Chemistry, Columbia University, New York, New York 10028, USA
J Biol Chem 278:18207-13. 2003..Conversely, vitamin C and ginkgolide B were not efficient quenchers of singlet oxygen under these conditions...
DNA is a target of the photodynamic effects elicited in A2E-laden RPE by blue-light illuminationJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Invest Ophthalmol Vis Sci 44:2245-51. 2003..This study was designed to determine whether DNA is a target of the cellular damage...
Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2J R Sparrow
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Invest Ophthalmol Vis Sci 42:1356-62. 2001..The purpose of this study was to evaluate caspase-3 and Bcl-2 as executor and modulator, respectively, of the cell death program that is initiated in A2E-containing cells in response to blue light...
A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in cultureJ R Sparrow
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Invest Ophthalmol Vis Sci 40:2988-95. 1999..To study A2E, a component of retinal pigmented epithelial (RPE) cell lipofuscin, after its internalization by cultured human RPE cells...
The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cellsJ R Sparrow
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Invest Ophthalmol Vis Sci 41:1981-9. 2000..To determine whether the lipofuscin fluorophore A2E participates in blue light-induced damage to retinal pigmented epithelial (RPE) cells...
Biosynthetic studies of A2E, a major fluorophore of retinal pigment epithelial lipofuscinShimon Ben-Shabat
Department of Chemistry, Columbia University, New York, NY 10028, USA
J Biol Chem 277:7183-90. 2002..The identities of additional minor components of retinal pigment epithelium lipofuscin, A2E isomers with cis olefins at positions other than the C13-C14 double bond, are also described...
Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscinYoung P Jang
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
J Biol Chem 280:39732-9. 2005..Because the cytotoxicity of endoperoxide moieties is well known, the production of endoperoxide-containing oxo-A2E may account, at least in part, for cellular damage ensuing from A2E photooxidation...
Characterization of dihydro-A2PE: an intermediate in the A2E biosynthetic pathwaySo R Kim
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Biochemistry 46:10122-9. 2007..An understanding of the biosynthetic pathways of retinal pigment epithelial lipofuscin pigments is critical to the development of therapies for macular degeneration that are based on limiting the formation of these damaging compounds...
Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt diseaseYalin Wu
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
J Biol Chem 284:20155-66. 2009..Efforts to clarify the composition of RPE lipofuscin are important because these compounds are targets of gene-based and drug therapies that aim to alleviate ABCA4-related retinal disease...
The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease modelSo R Kim
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 104:19273-8. 2007..The latter findings are significant to an understanding of the adverse effects of retinal pigment epithelial cell lipofuscin...
Fluorescent pigments of the retinal pigment epithelium and age-related macular degenerationS Ben-Shabat
Department of Chemistry, Columbia University, New York, NY 10027, USA
Bioorg Med Chem Lett 11:1533-40. 2001..Recent chemical and biological studies have provided insight into the synthesis and biosynthesis of A2E, the spectroscopic properties of this pigment, and the role of A2E and RPE cell death...
Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cellsYoung P Jang
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Photochem Photobiol 81:529-36. 2005..Cells that had taken up anthocyanins also exhibited a resistance to the membrane permeabilization that occurs as a result of the detergent-like action of A2E...
Immunochemical recognition of A2E, a pigment in the lipofuscin of retinal pigment epithelial cellsChandima Abeywickrama
Department of Chemistry, Columbia University, New York, NY 10027, USA
Proc Natl Acad Sci U S A 104:14610-5. 2007..The changes in fluorescence emission upon antibody binding could reflect several processes including restrictions on trans-cis isomerization and intersystem crossing of photo-excited A2E...
Structural characterization of bisretinoid A2E photocleavage products and implications for age-related macular degenerationYalin Wu
Department of Ophthalmology, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Proc Natl Acad Sci U S A 107:7275-80. 2010..Whereas various processes play a role in drusen formation, these findings are indicative of a contribution from lipofuscin photooxidation in RPE...
A2E, a fluorophore of RPE lipofuscin, can destabilize membraneJanet R Sparrow
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Adv Exp Med Biol 572:63-8. 2006
Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epitheliumJilin Zhou
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 103:16182-7. 2006..These findings link four factors that have been posited as being associated with AMD: inflammation, oxidative damage, drusen, and RPE lipofuscin...
Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthinSo Ra Kim
Department of Ophthalmology, Columbia University, NY 10032, USA
Exp Eye Res 82:828-39. 2006....
Isolation and characterization of a retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugateNathan E Fishkin
Department of Chemistry, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 102:7091-6. 2005....
OT-674 suppresses photooxidative processes initiated by an RPE lipofuscin fluorophoreJilin Zhou
Department of Ophthalmology, Columbia University, New York, NY, USA
Photochem Photobiol 84:75-80. 2008..As oxidative damage to RPE cells is considered to be a risk factor for AMD, antioxidant therapy with OT-674 may serve a protective role...
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 lightBarbro S Westlund
Department of Ophthalmology, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Apoptosis 14:31-41. 2009..This study indicates that c-Abl and p53 are important for execution of the cell death program initiated in A2E-laden RPE cells exposed to blue light, while JNK might play an anti-apoptotic role...
Mechanisms involved in A2E oxidationSo Ra Kim
Department of Ophthalmology, Columbia University, 630 W 168th Street, NY 10032, USA
Exp Eye Res 86:975-82. 2008..Superoxide anion may be generated by irradiation of A2E but is not involved in the early events that oxidize A2E. Superoxide can contribute to the further oxidation of already-oxidized A2E...
Scotopic sensitivity and color vision with a blue-light-absorbing intraocular lensVivienne C Greenstein
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
J Cataract Refract Surg 33:667-72. 2007..To investigate possible adverse effects of a yellow-tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination...
Complement activation by bisretinoid constituents of RPE lipofuscinJilin Zhou
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Invest Ophthalmol Vis Sci 50:1392-9. 2009..Questions pertain to the trigger(s) responsible for the complement-associated events. The authors previously reported that photooxidation products of A2E can activate complement. Here they have further explored these events...
Chlorophyll derivatives as visual pigments for super vision in the redIlyas Washington
Columbia University, Department of Chemistry, New York, NY 10027, USA
Photochem Photobiol Sci 6:775-9. 2007..Electroretinographic b-wave amplitudes recorded in response to red and blue light were two-fold greater in mice administered chlorin e(6), which accumulated in photoreceptor outer segments...
Photographic patterns in macular images: representation by a mathematical modelR Theodore Smith
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
J Biomed Opt 9:162-72. 2004..A two-zone elliptic quadratic polynomial model can approximate foveal data, and can also reconstruct it from small subsets, allowing improved macular image analysis...
Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2ESo Ra Kim
Department of Ophthalmology, Columbia University, New York, NY 10027, USA
Proc Natl Acad Sci U S A 101:11668-72. 2004..Here we show that an amino acid variant in murine Rpe65, a visual-cycle protein required for the regeneration of 11-cis-retinal, is associated with reduced A2E accumulation...
A blue-blocking intraocular lens should be used in cataract surgeryRichard E Braunstein
Edward S. Harkness Eye Institute, Columbia University, New York, NY 10032, USA
Arch Ophthalmol 123:547-9. 2005
Autofluorescence characteristics of normal foveas and reconstruction of foveal autofluorescence from limited data subsetsR Theodore Smith
Department of Ophthalmology, Columbia University, New York, NY 10032, USA
Invest Ophthalmol Vis Sci 46:2940-6. 2005..To develop mathematical and geometric models of the nonuniform autofluorescence (AF) patterns of foveas of normal subjects and to reconstruct these models from limited subsets of data...
Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvementShimon Ben-Shabat
Department of Chemistry, Columbia University, New York, NY 10027, USA
Angew Chem Int Ed Engl 41:814-7. 2002
Indirect antioxidant protection against photooxidative processes initiated in retinal pigment epithelial cells by a lipofuscin pigmentJilin Zhou
Department of Ophthalmology, Columbia University, New York, New York 10032, USA
Rejuvenation Res 9:256-63. 2006..The present results indicate that the indirect antioxidant activity of plant-derived phase 2 inducers also may be potentially important...
Mechanisms for the induction of HNE- MDA- and AGE-adducts, RAGE and VEGF in retinal pigment epithelial cellsJilin Zhou
Department of Ophthalmology, Columbia University, 630 W. 168th St, New York, NY 10032, USA
Exp Eye Res 80:567-80. 2005....
How much blue light should an IOL transmit?M A Mainster
Department of Ophthalmology, University of Kansas Medical School, Kansas City, KS 66160 7379, USA
Br J Ophthalmol 87:1523-9. 2003....
Photochemistry of A1E, a retinoid with a conjugated pyridinium moiety: competition between pericyclic photooxygenation and pericyclizationSteffen Jockusch
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA
J Am Chem Soc 126:4646-52. 2004..If the singlet oxygen produced is quenched by the protonated solvent molecules faster than singlet oxygen reacts with A1E, then cyclization dominates...
A2-rhodopsin: a new fluorophore isolated from photoreceptor outer segmentsNathan Fishkin
Department of Chemistry, Columbia University, New York, NY 10027, USA
Org Biomol Chem 1:1101-5. 2003....
Experimental approaches to the study of A2E, a bisretinoid lipofuscin chromophore of retinal pigment epitheliumJanet R Sparrow
Departments of Ophthalmology and Pathology and Cell Biology, Columbia University, New York, NY 10032, USA
Methods Mol Biol 652:315-27. 2010..This approach allows for a population of RPE cells that have accumulated the lipofuscin fluorophore A2E in addition to A2E-free cells...
A method of drusen measurement based on reconstruction of fundus background reflectanceR T Smith
Harkness Eye Institute, Columbia University College of Pysicians and Surgeons, New York, NY 10032, USA
Br J Ophthalmol 89:87-91. 2005..Current manual methods of drusen segmentation and quantification are laborious and subjective. The authors introduced a digital method and tested it for accuracy and reliability...
Absolute configurational determination of an all-trans-retinal dimer isolated from photoreceptor outer segmentsNathan Fishkin
Department of Chemistry, Columbia University, New York, NY 10027, USA
Chirality 16:637-41. 2004..This further suggested that despite the large energy difference between the two interacting chromophores, the dominant source of optical activity in the CD spectrum is the nondegenerate exciton mechanism...
SOD2 knockdown mouse model of early AMDVerline Justilien
Department of Molecular Genetics, University of Florida, Gainesville, Florida, USA
Invest Ophthalmol Vis Sci 48:4407-20. 2007..To test the hypothesis that oxidative injury to the retinal pigment epithelium (RPE) may lead to retinal damage similar to that associated with the early stages of age-related macular degeneration (AMD)...
The proteasome: a target of oxidative damage in cultured human retina pigment epithelial cellsXinyu Zhang
United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA
Invest Ophthalmol Vis Sci 49:3622-30. 2008..The objective of this study was to investigate the effect of oxidative stress on the UPP in cultured human retina pigment epithelial cells...
Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseasesAubrey D N J de Grey
Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK
Ageing Res Rev 4:315-38. 2005..We discuss how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose and ways to avoid potential side-effects...
Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formationPranab Maiti
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Biochemistry 45:852-60. 2006..These antagonists will also be used to probe the molecular function of RPE65 in vision...
Retinal pigment epithelium lipofuscin proteomicsKwok Peng Ng
Cole Eye Institute and Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University, Cleveland, Ohio 44195, USA
Mol Cell Proteomics 7:1397-405. 2008....
Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in miceMariacarmela Allocca
Telethon Institute of Genetics and Medicine TIGEM, Naples, Italy
J Clin Invest 118:1955-64. 2008..The possibility of packaging large genes in AAV greatly expands the therapeutic potential of this vector system...
Research Grants
- IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLSJanet R Sparrow; Fiscal Year: 2010....
- IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLSJanet Sparrow; Fiscal Year: 2006..The long-term goals of this work are to develop therapies that would reduce the formation of A2E, destroy the formed molecule within the RPE cell, or counter the deleterious effects of its accumulation. ..
- IMPACT OF LIPOFUSCIN IN RETINAL PIGMENT EPITHELIAL CELLSJanet Sparrow; Fiscal Year: 2002..If it can be demonstrated that the amassing of synthetic A2E by RPE cells is significant in terms of RPE cell function, treatments could be aimed at preventing its formation or destroying the formed molecule within the RPE cells. ..
- NEUTROPHINS AND RETINAL DEVELOPMENTJanet Sparrow; Fiscal Year: 2001..The use of neurotrophins in conjunction with gene therapy or transplantation may also have potential for reversing retinal degenerative changes and lead to the restoration of vision. ..
