Experts and Doctors on eye proteins in Philadelphia, Pennsylvania, United States


Locale: Philadelphia, Pennsylvania, United States
Topic: eye proteins

Top Publications

  1. Ahmad M, Cashmore A. The blue-light receptor cryptochrome 1 shows functional dependence on phytochrome A or phytochrome B in Arabidopsis thaliana. Plant J. 1997;11:421-7 pubmed
    ..It was concluded that CRY1-mediated inhibition of hypocotyl elongation and anthocyanin production requires active phytochrome for full expression, and that this requirement can be supplied by low levels of either phyA or phyB. ..
  2. Bonini N, Leiserson W, Benzer S. Multiple roles of the eyes absent gene in Drosophila. Dev Biol. 1998;196:42-57 pubmed
    ..Despite multiple roles at multiple stages of development of the fly, both the type I and type II forms of the protein, when expressed ectopically during larval development, can direct eye formation. ..
  3. Jacobson S, Cideciyan A, Aleman T, Sumaroka A, Roman A, Swider M, et al. Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Invest Ophthalmol Vis Sci. 2011;52:70-9 pubmed publisher
    ..The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study. ..
  4. Lin F, Song W, Meyer Bernstein E, Naidoo N, Sehgal A. Photic signaling by cryptochrome in the Drosophila circadian system. Mol Cell Biol. 2001;21:7287-94 pubmed
    ..High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination. ..
  5. Cideciyan A, Zhao X, Nielsen L, Khani S, Jacobson S, Palczewski K. Null mutation in the rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man. Proc Natl Acad Sci U S A. 1998;95:328-33 pubmed
    ..Cones may rely mainly on regeneration for the inactivation of photolyzed visual pigment, but RK also contributes to cone recovery. ..
  6. Jacobson S, Cideciyan A, Aleman T, Sumaroka A, Schwartz S, Windsor E, et al. RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression. Invest Ophthalmol Vis Sci. 2007;48:332-8 pubmed
    ..The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12. ..
  7. Cashmore A, Jarillo J, Wu Y, Liu D. Cryptochromes: blue light receptors for plants and animals. Science. 1999;284:760-5 pubmed
    ..This process of repeated evolution may have coincided with the origin in animals of a modified circadian clock based on the PERIOD, TIMELESS, CLOCK, and CYCLE proteins. ..
  8. Pierce E, Quinn T, Meehan T, McGee T, Berson E, Dryja T. Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat Genet. 1999;22:248-54 pubmed
    ..Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology. ..
  9. Jeong Y, Leskow F, El Jaick K, Roessler E, Muenke M, Yocum A, et al. Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein. Nat Genet. 2008;40:1348-53 pubmed publisher
    ..Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE. ..

More Information


  1. Daniele L, Adams R, Durante D, Pugh E, Philp N. Novel distribution of junctional adhesion molecule-C in the neural retina and retinal pigment epithelium. J Comp Neurol. 2007;505:166-76 pubmed
    ..The nonclassical distribution of Jam-C in the apical membranes of Müller cells and RPE suggests that Jam-C has a novel function in the retina. ..
  2. Zhou J, Wang C, Wang Z, Dampier W, Wu K, Casimiro M, et al. Attenuation of Forkhead signaling by the retinal determination factor DACH1. Proc Natl Acad Sci U S A. 2010;107:6864-9 pubmed publisher
    ..Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis. ..
  3. Jacobson S, Cideciyan A, Aleman T, Sumaroka A, Windsor E, Schwartz S, et al. Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci. 2008;49:4573-7 pubmed publisher
  4. Iacovelli J, Zhao C, Wolkow N, Veldman P, Gollomp K, Ojha P, et al. Generation of Cre transgenic mice with postnatal RPE-specific ocular expression. Invest Ophthalmol Vis Sci. 2011;52:1378-83 pubmed publisher
    ..These mice should facilitate study of the multifunctional RPE and the generation of mouse models of human retinal disease. ..
  5. Zhou J, Liu Y, Zhang W, Popov V, Wang M, Pattabiraman N, et al. Transcription elongation regulator 1 is a co-integrator of the cell fate determination factor Dachshund homolog 1. J Biol Chem. 2010;285:40342-50 pubmed publisher
    ..Thus, DACH1 represses gene transcription through direct DNA binding to the promoter region of target genes by recruiting the transcriptional co-regulator, TCERG1. ..
  6. Koh K, Zheng X, Sehgal A. JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS. Science. 2006;312:1809-12 pubmed
    ..Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM. ..
  7. Fabrizio J, Boyle M, Dinardo S. A somatic role for eyes absent (eya) and sine oculis (so) in Drosophila spermatocyte development. Dev Biol. 2003;258:117-28 pubmed
  8. Jacobson S, Cideciyan A, Aleman T, Pianta M, Sumaroka A, Schwartz S, et al. Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet. 2003;12:1073-8 pubmed
    ..The results suggest that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis. ..
  9. Jacobson S, Aleman T, Cideciyan A, Heon E, Golczak M, Beltran W, et al. Human cone photoreceptor dependence on RPE65 isomerase. Proc Natl Acad Sci U S A. 2007;104:15123-8 pubmed
  10. Cohen M, Hud E, Shea E, Shearman C. Vitreous fluid of db/db mice exhibits alterations in angiogenic and metabolic factors consistent with early diabetic retinopathy. Ophthalmic Res. 2008;40:5-9 pubmed
    ..The findings support the potential usefulness of vitreous from the db/db mouse as a model tissue for investigation of pathogenetic factors and assessment of therapeutic interventions in early diabetic retinopathy. ..
  11. Frara N, Abdelmagid S, Sondag G, Moussa F, Yingling V, Owen T, et al. Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo. J Cell Physiol. 2016;231:72-83 pubmed publisher
    ..Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. ..
  12. Lin C, Ahmad M, Cashmore A. Arabidopsis cryptochrome 1 is a soluble protein mediating blue light-dependent regulation of plant growth and development. Plant J. 1996;10:893-902 pubmed
    ..It is concluded that CRY1 is a photoreceptor mediating blue light-dependent regulation of gene expression in addition to its affect on plant growth. ..
  13. Jarillo J, Capel J, Tang R, Yang H, Alonso J, Ecker J, et al. An Arabidopsis circadian clock component interacts with both CRY1 and phyB. Nature. 2001;410:487-90 pubmed
    ..Both yeast two-hybrid and in vitro binding studies show that there is a physical interaction between ADO1 and the photoreceptors CRY1 and phyB. We propose that ADO1 is an important component of the Arabidopsis circadian system. ..
  14. Caruso R, Aleman T, Cideciyan A, Roman A, Sumaroka A, Mullins C, et al. Retinal disease in Rpe65-deficient mice: comparison to human leber congenital amaurosis due to RPE65 mutations. Invest Ophthalmol Vis Sci. 2010;51:5304-13 pubmed publisher
  15. Popov V, Wu K, Zhou J, Powell M, Mardon G, Wang C, et al. The Dachshund gene in development and hormone-responsive tumorigenesis. Trends Endocrinol Metab. 2010;21:41-9 pubmed publisher
    ..The molecular mechanisms by which DACH1 regulates differentiation and tumorigenesis are discussed herein. ..
  16. Schwartz S, Aleman T, Cideciyan A, Swaroop A, Jacobson S, Stone E. De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2003;44:3593-7 pubmed
  17. Aguirre G, Komaromy A, Cideciyan A, Brainard D, Aleman T, Roman A, et al. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Med. 2007;4:e230 pubmed
    ..We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA)...
  18. Zimmerman J, Mackiewicz M, Galante R, Zhang L, Cater J, Zoh C, et al. Glycogen in the brain of Drosophila melanogaster: diurnal rhythm and the effect of rest deprivation. J Neurochem. 2004;88:32-40 pubmed
    ..0001 and p<0.0001, respectively). Glycogen in the fly brain changes in relationship to rest and activity and demonstrates a biphasic response to rest deprivation similar to that observed in mammalian astrocytes in culture. ..
  19. Du A, Hunter C, Murray J, Noble D, Cai C, Evans S, et al. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes. 2009;58:2059-69 pubmed publisher
    ..These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. ..
  20. Abdelmagid S, Barbe M, Rico M, Salihoglu S, Arango Hisijara I, Selim A, et al. Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function. Exp Cell Res. 2008;314:2334-51 pubmed publisher
    ..Collectively, our data suggest that OA acts as a positive regulator of osteoblastogenesis. ..
  21. Alvarado D, Evans T, Sharma R, Lemmon M, Duffy J. Argos mutants define an affinity threshold for spitz inhibition in vivo. J Biol Chem. 2006;281:28993-9001 pubmed
    ..In agreement with previously reported computational studies, our results define an affinity threshold for optimal Argos inhibition of dEGFR signaling during development. ..
  22. Cideciyan A. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res. 2010;29:398-427 pubmed publisher
    ..This article reviews the current knowledge on retinal degeneration and visual dysfunction in animal models and human patients with RPE65 disease, and examines the consequences of gene therapy in terms of improvement of vision reported. ..
  23. Philp N, Chu P, Pan T, Zhang R, Chu M, Stark K, et al. Developmental expression and molecular cloning of REMP, a novel retinal epithelial membrane protein. Exp Cell Res. 1995;219:64-73 pubmed
    ..The unique expression of REMP in the RPE in vivo would suggest a role for this protein in development and maintenance of normal retinal function. ..
  24. Yang Z, Emerson M, Su H, Sehgal A. Response of the timeless protein to light correlates with behavioral entrainment and suggests a nonvisual pathway for circadian photoreception. Neuron. 1998;21:215-23 pubmed
    ..These results support the hypothesis that circadian entrainment does not rely on the visual system and likely involves a dedicated pathway for photoreception. ..
  25. Aleman T, Cideciyan A, Aguirre G, Huang W, Mullins C, Roman A, et al. Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model. Invest Ophthalmol Vis Sci. 2011;52:6898-910 pubmed publisher
    ..Differences between human and mouse diseases will complicate proof-of-concept studies intended to advance treatment initiatives. ..
  26. Jacobson S, Aleman T, Cideciyan A, Roman A, Sumaroka A, Windsor E, et al. Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci. 2009;50:2368-75 pubmed publisher
    ..The finding of different regional patterns of visual loss in these patients suggests that the optimal retinal site(s) for subretinal gene delivery to achieve efficacy are likely to change with disease progression. ..
  27. Liu Q, Zuo J, Pierce E. The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein. J Neurosci. 2004;24:6427-36 pubmed
    ..Furthermore, these findings indicate that the RP1 form of inherited retinal degeneration is part of the larger class of neurodegenerative diseases caused by MAP dysfunction. ..
  28. Popov V, Zhou J, Shirley L, Quong J, Yeow W, Wright J, et al. The cell fate determination factor DACH1 is expressed in estrogen receptor-alpha-positive breast cancer and represses estrogen receptor-alpha signaling. Cancer Res. 2009;69:5752-60 pubmed publisher
    ..DACH1 expression, which is lost in poor prognosis human breast cancer, functions as an endogenous inhibitor of ERalpha function. ..
  29. Karakousis P, John S, Behling K, Surace E, Smith J, Hendrickson A, et al. Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis. 2001;7:154-63 pubmed
    ..PEDF, originally reported as a product of RPE cells, is present in photoreceptors and inner retinal cell types in developing and adult human eyes. Photoreceptors and RPE may secrete PEDF into the IPM. ..
  30. Kumar S, Chen D, Sehgal A. Dopamine acts through Cryptochrome to promote acute arousal in Drosophila. Genes Dev. 2012;26:1224-34 pubmed publisher
    ..We propose that CRY has a distinct role in acute responses to sensory stimuli: (1) circadian responses to light, as previously reported, and (2) noncircadian effects on arousal, as shown here. ..
  31. Pignolo R, Cristofalo V, Rotenberg M. Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state. J Biol Chem. 1993;268:8949-57 pubmed
    ..These findings support the hypothesis that senescent WI-38 cells exhibit a state of growth arrest fundamentally distinct from that of quiescent (G0) young cells. ..
  32. Jacobson S, Cideciyan A, Aleman T, Sumaroka A, Roman A, Gardner L, et al. Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism. Hum Mol Genet. 2008;17:2405-15 pubmed publisher
    ..The results point to the photoreceptor cell as the therapeutic target for USH treatment trials, such as MYO7A somatic gene replacement therapy. ..
  33. Jacobson S, Aleman T, Cideciyan A, Sumaroka A, Schwartz S, Windsor E, et al. Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganization. Mol Vis. 2009;15:1098-106 pubmed
    ..Detailed phenotype studies in other LCA5 patients with longitudinal follow-up will help determine the feasibility of future intervention in this rare disease. ..
  34. Jacobson S, Aleman T, Cideciyan A, Sumaroka A, Schwartz S, Windsor E, et al. Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Proc Natl Acad Sci U S A. 2005;102:6177-82 pubmed
  35. Nikonov S, Daniele L, Zhu X, Craft C, Swaroop A, Pugh E. Photoreceptors of Nrl -/- mice coexpress functional S- and M-cone opsins having distinct inactivation mechanisms. J Gen Physiol. 2005;125:287-304 pubmed
    ..Thus, Grk1 is essential to normal inactivation of both S- and M-mouse cone opsins, but S-opsin has access to a relatively effective, Grk1-independent inactivation pathway. ..
  36. Vrabec T, Tantri A, Edwards A, Frost A, Donoso L. Autosomal dominant Stargardt-like macular dystrophy: identification of a new family with a mutation in the ELOVL4 gene. Am J Ophthalmol. 2003;136:542-5 pubmed
    ..We characterized a new branch of a family with autosomal dominant Stargardt-like macular dystrophy. Identification of the disease-causing gene allows for improved genetic counseling of affected individuals. ..
  37. Valentine K, Mesleh M, Opella S, Ikura M, Ames J. Structure, topology, and dynamics of myristoylated recoverin bound to phospholipid bilayers. Biochemistry. 2003;42:6333-40 pubmed
    ..These results demonstrate that membrane binding by recoverin is achieved primarily by insertion of the myristoyl group inside the bilayer with apparently little rearrangement of the protein structure. ..
  38. Yang H, Tang R, Cashmore A. The signaling mechanism of Arabidopsis CRY1 involves direct interaction with COP1. Plant Cell. 2001;13:2573-87 pubmed
    ..These findings give new insight into the initial step in light signaling in Arabidopsis, providing a molecular link between the blue light receptor, CRY1, and COP1, a negative regulator of photomorphogenesis. ..
  39. Bui Q, Zimmerman J, Liu H, Bonini N. Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain. Genetics. 2000;155:709-20 pubmed
    ..Taken together, these data suggest that the conserved Eya Domain is critical for eya activity and may have functional subregions within it. ..
  40. Jacobson S, Cideciyan A, Bennett J, Kingsley R, Sheffield V, Stone E. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy. Arch Ophthalmol. 2002;120:376-9 pubmed
  41. Kunapuli P, Benovic J. Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proc Natl Acad Sci U S A. 1993;90:5588-92 pubmed
    ..Thus, GRK5 represents a member of the GRK family that likely has a unique physiological role. ..
  42. Huang W, Wright A, Roman A, Cideciyan A, Manson F, Gewaily D, et al. RPGR-associated retinal degeneration in human X-linked RP and a murine model. Invest Ophthalmol Vis Sci. 2012;53:5594-608 pubmed publisher
    ..We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model...
  43. Ahmad M, Jarillo J, Smirnova O, Cashmore A. The CRY1 blue light photoreceptor of Arabidopsis interacts with phytochrome A in vitro. Mol Cell. 1998;1:939-48 pubmed
    ..In vivo labeling studies and specific mutant alleles of CRY1, which interfere with the function of phytochrome, suggest the possible relevance of these findings in vivo. ..
  44. Perez M, Paulson H, Pendse S, Saionz S, Bonini N, Pittman R. Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol. 1998;143:1457-70 pubmed
    ..In addition, we demonstrate that the nuclear environment may be critical for seeding polyglutamine aggregates...
  45. Golden J, Bracilovic A, McFadden K, Beesley J, Rubenstein J, Grinspan J. Ectopic bone morphogenetic proteins 5 and 4 in the chicken forebrain lead to cyclopia and holoprosencephaly. Proc Natl Acad Sci U S A. 1999;96:2439-44 pubmed
    ..These data provide evidence that BMP signaling participates in dorsal-ventral patterning of the developing brain in vivo, and disturbances in dorsal-ventral signaling result in specific malformations of the forebrain. ..
  46. Lyubarsky A, Chen C, Simon M, Pugh E. Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. J Neurosci. 2000;20:2209-17 pubmed
  47. John S, Smith J, Aguirre G, Milam A. Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa. Mol Vis. 2000;6:204-15 pubmed
    ..Such cytologic and immunocytochemical changes in the cones may presage death of these critical cells in the later stages of RP. ..
  48. Aleman T, Cideciyan A, Sumaroka A, Schwartz S, Roman A, Windsor E, et al. Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations. Invest Ophthalmol Vis Sci. 2007;48:4759-65 pubmed
    ..These results should be factored into emerging therapeutic strategies for this form of RP. ..
  49. Hahn P, Lindsten T, Ying G, Bennett J, Milam A, Thompson C, et al. Proapoptotic bcl-2 family members, Bax and Bak, are essential for developmental photoreceptor apoptosis. Invest Ophthalmol Vis Sci. 2003;44:3598-605 pubmed
    ..Future studies will investigate the potential role of Bax and Bak in mediating pathologic photoreceptor death. ..
  50. Aleman T, Jacobson S, Chico J, Scott M, Cheung A, Windsor E, et al. Impairment of the transient pupillary light reflex in Rpe65(-/-) mice and humans with leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2004;45:1259-71 pubmed
    ..The objective and noninvasive nature of the TPLR measurement, and the observed post-treatment change toward normal in the animal model supports the notion that this may be a useful outcome measure in future therapeutic trials of LCA. ..
  51. Patel K, Bartoli K, Fandino R, Ngatchou A, Woch G, Carey J, et al. Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel. Invest Ophthalmol Vis Sci. 2005;46:2282-90 pubmed
    ..Examination of mutations that cluster in the first transmembrane segment of the protein may provide insight into its role in CNG channel structure, function, biogenesis, and pathophysiology...
  52. Kim D, Neely K, Sassani J, Vrabec T, Tantri A, Frost A, et al. X-linked retinoschisis: novel mutation in the initiation codon of the XLRS1 gene in a large family. Retina. 2006;26:940-6 pubmed
  53. Franklin Dumont T, Chatterjee C, Wasserman S, Dinardo S. A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes. Development. 2007;134:2851-61 pubmed
    ..Based on these studies, we speculate that spermatocytes monitor G(2) growth as one means to coordinate the initiation of meiotic division and differentiation. ..