Advances in Experimental Medicine and Biology Journal Impact Factor & Information

Publisher: Kluwer

Current impact factor: 1.96

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 1.958
2012 Impact Factor 1.825
2011 Impact Factor 1.093
2010 Impact Factor 1.379
2009 Impact Factor 2.02
2008 Impact Factor 0.663
2007 Impact Factor 0.663
2006 Impact Factor 0.646
2005 Impact Factor 0.635
2004 Impact Factor 0.642
2000 Impact Factor 0.513
1999 Impact Factor 0.446
1998 Impact Factor 0.36

Impact factor over time

Impact factor

Additional details

5-year impact 1.70
Cited half-life 6.30
Immediacy index 0.59
Eigenfactor 0.03
Article influence 0.56
Website Advances in Experimental Medicine & Biology website
Other titles Advances in experimental medicine and biology, Experimental medicine and biology
ISSN 0065-2598
OCLC 1461189
Material type Series
Document type Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors own final version can be archived
    • Publisher's protected PDF can be used for a fee
    • Published source must be acknowledged
    • Must link to publisher version
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Kluwer' is an imprint of 'Springer Verlag (Germany)'
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The expression of X-linked genes is equalized between males and females in mammalian species through X-Chromosome inactivation (XCI). Every cell in a female mammalian embryo randomly chooses one X Chromosome for epigenetic silencing at the 8–16 cell stage, resulting in a Gaussian distribution of XCI ratios with a peak at 50:50. At the tail extremes of this distribution, X-linked recessive mutations can manifest in disease in female carriers if the mutant allele is disproportionately active. The role of XCI skewing, if any, in X-linked retinal disease is still unknown, although many have speculated that such skewing accounts for phenotypic variation in female carriers of X-linked retinitis pigmentosa (XlRP). Some investigators have used clinical findings such as tapetal-like reflex, pigmentary changes, and multifocal ERG parameters to approximate XCI patches in the retina. These studies are limited by small cohorts and the relative inaccessibility of retinal tissue for genetic and epigenetic analysis. Although blood has been used as a proxy for other tissues in determining XCI ratios, blood XCI skews with age out of proportion to other tissues and may not accurately reflect retinal XCI ratios. Future investigations in determining retinal XCI ratios and the contribution of XCI to phenotype could potentially impact prognosis for female carriers of X-linked retinal disease.
    Advances in Experimental Medicine and Biology 10/2016; 854:325-331. DOI:10.1007/978-3-319-17121-0_43
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    ABSTRACT: During different forms of neurodegenerative diseases, including the retinal degeneration, several cell cycle proteins are expressed in the dying neurons from Drosophila to human revealing that these proteins are a hallmark of neuronal degeneration. This is true for animal models of Alzheimer’s, and Parkinson’s diseases, Amyotrophic Lateral Sclerosis and for Retinitis Pigmentosa as well as for acute injuries such as stroke and light damage. Longitudinal investigation and loss-of-function studies attest that cell cycle proteins participate to the process of cell death although with different impacts, depending on the disease. In the retina, inhibition of cell cycle protein action can result to massive protection. Nonetheless, the dissection of the molecular mechanisms of neuronal cell death is necessary to develop adapted therapeutic tools to efficiently protect photoreceptors as well as other neuron types.
    Advances in Experimental Medicine and Biology 10/2016; 854:371-377. DOI:10.1007/978-3-319-17121-0_49
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    ABSTRACT: We present an optimized surgical technique for feline retinal detachment which allows for natural re-attachment, reduces retinal scarring and vitreal bands, and allows central placement of the detachment in close proximity to the optic nerve. This enables imaging via Optical Coherence Tomography (OCT) and multifocal electroretinography (mfERG) analysis. Ideal detachment conditions involve a lensectomy followed by a three-port pars plana vitrectomy. A 16–20 % retinal detachment is induced by injecting 8 % C3F8 gas into the subretinal space in the central retina with a 42G cannula. The retinal detachment resolves approximately 6 weeks post-surgery. Imaging is enhanced by using a 7.5 and 20 diopter lens for OCT and mfERG fundus imaging, respectively, to compensate for the removed lens.
    Advances in Experimental Medicine and Biology 10/2016; 854:315-321. DOI:10.1007/978-3-319-17121-0_42
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    ABSTRACT: One of the affected tissues in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), a tissue that consists of terminally differentiated cells and that accumulates damage over time. In all tissues, mitochondria (mt), which play an essential role in both cell health (energy) and death (initiator of apoptosis), undergo an aging process through the accumulation of mtDNA damage, changes in mitochondrial dynamics, a reduction in biogenesis, and mitophagy, leading to an overall reduction in mitochondrial energy production and other nonenergy- related functions. Here we have compared energy metabolism in primary human RPE cells isolated from aborted fetus or aged donor eyes and grown as stable monolayers. H2O2 treatment resulted in the generation of reactive oxygen species and superoxide, an effect that was significantly augmented by age. Mitochondrial metabolism, as analyzed by Seahorse respirometry, revealed reduced mitochondrial oxygen consumption (ATP production) at baseline and a complete loss of reserve capacity in aged cells. Likewise, glycolysis was blunted in aged cells. Taken together, these studies showed that RPE cells derived from aged donor eyes are more susceptible to oxidative stress, and exhibit a loss in mitochondrial respiratory reserve capacity and a reduction in glycolysis. These data suggest that while old cells may have sufficient energy at rest, they cannot mount a stress response requiring additional ATP and reducing agents. In summary, these data support the hypothesis that mitochondria or energy metabolism is a valid target for therapy in AMD.
    Advances in Experimental Medicine and Biology 10/2016; 854:793-798. DOI:10.1007/978-3-319-17121-0_106
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    ABSTRACT: Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.
    Advances in Experimental Medicine and Biology 10/2016; 854:677-683. DOI:10.1007/978-3-319-17121-0_90
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    ABSTRACT: The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer situated between the light-sensitive photoreceptors and the choriocapillaris. Given its vital functions for healthy vision, the RPE is a primary target for insults that result in blinding diseases, including age-related macular degeneration (AMD). One such function is the phagocytosis and digestion of shed photoreceptor outer segments. In the present study, we examined the process of trafficking of outer segment disk membranes in live cultures of primary mouse RPE, using high speed spinning disk confocal microscopy. This approach has enabled us to track phagosomes, and determine parameters of their motility, which are important for their efficient degradation.
    Advances in Experimental Medicine and Biology 10/2016; 854:751-755. DOI:10.1007/978-3-319-17121-0_100
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    ABSTRACT: We are interested in the roles of epigenetic mechanisms in retinal development. By ChIP-qPCR using whole retinal extracts at various developmental stages, we found that the levels of methylation of histones H3K27 and H3K4 and acetylation of histone H3 at specific loci in various genes, which play critical roles in retinal proliferation and differentiation, changed dramatically during retinal development. We next focused on the roles of H3K27 trimethylation in retinal development. Ezh1 and Ezh2 are methyltransferases that act on H3K27, while Jmjd3 and Utx are demethylases. We found that Ezh2 and Jmjd3 were mainly expressed during retinal development, and a loss-of-function of these genes revealed a role for H3K27me3 in the maturation of subsets of bipolar cells. Furthermore, Ezh2 and Jmjd3 regulate H3K27 trimethylation at specific loci within Bhlhb4 and Vsx1, which play critical roles in the differentiation of subsets of bipolar cells. Utx is expressed weakly in retina, and the down-regulation of Utx by sh-RNA in retinal explants suggested that Utx also participates in the maturation of bipolar cells. Ezh1 is expressed weakly in postnatal retina, and the phenotype of Ezh2-knockout retina suggested that Ezh1 plays a role in the methylation of H3K27 in the late phase of retinal differentiation. Taken together, we found that these four genes, which exhibit temporally and spatially unique expression patterns during retinal development, play critical roles in the differentiation of retinal subsets through the regulation of histone H3K27 methylation at critical genetic loci.
    Advances in Experimental Medicine and Biology 10/2016; 854:635-641. DOI:10.1007/978-3-319-17121-0_84
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    ABSTRACT: Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.0 at 0 % recombination in a sixgeneration family with autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked RP genes were excluded in the family by a combination of methods. Whole-exome next-generation sequencing revealed a missense mutation in hexokinase 1, HK1 c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members. One severely-affected male is homozygous for this region by linkage analysis and has two copies of the mutation. No other potential mutations were detected in the linkage region nor were any candidates identified elsewhere in the genome. Subsequent testing detected the same mutation in four additional, unrelated adRP families, for a total of five mutations in 404 probands tested (1.2 %). Of the five families, three are from the Acadian population in Louisiana, one is French Canadian and one is Sicilian. Haplotype analysis of the affected chromosome in each family and the homozygous individual revealed a rare, shared haplotype of 450 kb, suggesting an ancient founder mutation. HK1 is a widelyexpressed gene, with multiple, abundant retinal transcripts, coding for hexokinase 1. Hexokinase catalyzes phosphorylation of glucose to glusose-6-phospate, the first step in glycolysis. The Glu847Lys mutation is in a highly-conserved site, outside of the active site or known functional sites.
    Advances in Experimental Medicine and Biology 10/2016; 854:193-200. DOI:10.1007/978-3-319-17121-0_26
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    ABSTRACT: Retinal degeneration (RD) such as retinitis pigmentosa and agerelated macular degeneration are major causes of blindness in adulthood. As one of the model for RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used because of its selective photoreceptor cell death. It has been reported that MNU increases intracellular calcium ions in the retina and induces photoreceptor cell death. Although calcium ion influx triggers the neuronal nitric oxide synthase (nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not been reported yet. In this study, we investigated the contribution of nNOS on photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS activation at 3 day after treatment. Then, we evaluated the effect of nNOS specific inhibitor, ethyl[4-(trifluoromethyl) phenyl] carbamimidothioate (ETPI) on the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the MNU-induced cell death in the ONL. These data indicate that nNOS is a key molecule for pathogenesis of MNU-induced photoreceptor cell death.
    Advances in Experimental Medicine and Biology 10/2016; 854:379-384. DOI:10.1007/978-3-319-17121-0_50
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    ABSTRACT: Mutations in the BEST1 gene lead to a variety of retinal degenerations including Best’s vitelliforme macular degeneration. The BEST1 gene product, bestrophin-1, is expressed in the retinal pigment epithelium (RPE). It is likely that mutant bestrophin-1 impairs functions of the RPE which support photoreceptor function and will thus lead to retinal degeneration. However, the RPE function which is influenced by bestrophin-1 is so far not identified. Previously we showed that bestrophin-1 interacts with L-type Ca2++ channels of the CaV1.3 subtype and that the endogenously expressed bestrophin-1 is required for intracellular Ca2++ regulation. A hallmark of Best’s disease is the fast lipofuscin accumulation occurring already at young ages. Therefore, we addressed the hypothesis that bestrophin-1 might influence phagocytosis of photoreceptor outer segments (POS) by the RPE. Here, siRNA knock-down of bestrophin-1 expression as well as inhibition of L-type Ca2++ channel activity modulated the POS phagocytosis in vitro. In vivo CaV1.3 expression appeared to be diurnal regulated with a higher expression rate in the afternoon. Compared to wild-type littermates, CaV1.3−/− mice showed a shift in the circadian POS phagocytosis with an increased activity in the afternoon. Thus we suggest that mutant bestrophin-1 leads to an impaired regulation of the POS phagocytosis by the RPE which would explain the fast lipofuscin accumulation in Best patients.
    Advances in Experimental Medicine and Biology 10/2016; 854:739-744. DOI:10.1007/978-3-319-17121-0_98
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    ABSTRACT: Evidence is growing that exposure of tissue to low energy photon irradiation in the far-red (FR) to near-infrared (NIR) range of the spectrum, collectively termed “photobiomodulation” (PBM) can restore the function of damaged mitochondria, upregulate the production of cytoprotective factors and prevent apoptotic cell death. PBM has been applied clinically in the treatment of soft tissue injuries and acceleration of wound healing for more than 40 years. Recent studies have demonstrated that FR/NIR photons penetrate diseased tissues including the retina. The therapeutic effects of PBM have been hypothesized to result from intracellular signaling pathways triggered when FR/NIR photons are absorbed by the mitochondrial photoacceptor molecule, cytochrome c oxidase, culminating in improved mitochondrial energy metabolism, increased cytoprotective factor production and cell survival. Investigations in rodent models of methanol-induced ocular toxicity, light damage, retinitis pigmentosa and age-related macular degeneration have demonstrated the PBM attenuates photoreceptor cell death, protects retinal function and exerts anti-inflammatory actions.
    Advances in Experimental Medicine and Biology 10/2016; 854:437-441. DOI:10.1007/978-3-319-17121-0_58
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    ABSTRACT: Zebrafish can regenerate several organs such as the tail fin, heart, central nervous system, and photoreceptors. Very recently, a study has demonstrated the photoreceptor regeneration in the alkylating agent N-methyl-N-nitrosourea (MNU)- induced retinal degeneration (RD) zebrafish model, in which whole photoreceptors are lost within a week after MNU treatment and then regenerated within a month. The research has also shown massive proliferation of Müller cells within a week. To address the question of whether proliferating Müller cells are the source of regenerating photoreceptors, which remains unknown in the MNU-induced zebrafish RD model, we employed a BrdU pulse-chase technique to label the proliferating cells within a week after MNU treatment. As a result of the BrdU pulse-chase technique, a number of BrdU+ cells were observed in the outer nuclear layer as well as the inner nuclear layer. This implies that regenerating photoreceptors are derived from proliferating Müller cells in the zebrafish MNU-induced RD model.
    Advances in Experimental Medicine and Biology 10/2016; 854:685-692. DOI:10.1007/978-3-319-17121-0_91
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    ABSTRACT: One feature common to many of the pathways implicated in retinal degeneration is increased metabolic stress leading to impaired mitochondrial function. We found that exposure of cells to calcium ionophores or oxidants as metabolic stressors diminish maximal mitochondrial capacity. A library of 50,000 structurally diverse “drug-like” molecules was screened for protection against loss of calcium-induced loss of mitochondrial capacity in 661W rod-derived cells and C6 glioblastomas. Initial protective hits were then tested for protection against IBMX-induced loss of mitochondrial capacity as measured via respirometry. Molecules that protected mitochondria were then evaluated for protection of rod photoreceptor cells in retinal explants from rd1 mice. Two of the molecules attenuated loss of photoreceptor cells in the rd1 model. In the 661W cells, exposure to calcium ionophore or tertbutylhydroperoxide caused mitochondrial fragmentation that was blocked with the both compounds. Our studies have identified molecules that protect mitochondria and attenuate loss of photoreceptors in models of retinal degeneration suggesting that they could be good leads for development of therapeutic drugs for treatment of a wide variety of retinal dystrophies.
    Advances in Experimental Medicine and Biology 10/2016; 854:449-454. DOI:10.1007/978-3-319-17121-0_60
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    ABSTRACT: Age-related macular degeneration (AMD) is a multifactorial disorder that affects millions of individuals worldwide. While the advent of anti-VEGF therapy has allowed for effective treatment of neovascular ‘wet’ AMD, no treatments are available to mitigate the more prevalent ‘dry’ forms of the disease. A role for inflammatory processes in the progression of AMD has emerged over a period of many years, particularly the characterisation of leukocyte infiltrates in AMDaffected eyes, as well as in animal models. This review focuses on the burgeoning understanding of chemokines in the retina, and their potential role in shaping the recruitment and activation of macrophages in AMD. Understanding the mechanisms which promote macrophage activity in the degenerating retina may be key to controlling the potentially devastating consequences of inflammation in diseases such as AMD.
    Advances in Experimental Medicine and Biology 10/2016; 854:11-16. DOI:10.1007/978-3-319-17121-0_2
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    ABSTRACT: Dysregulated neuroinflammatory signaling during impending disruption of homeostasis in retinal pigment epithelium (RPE) and photoreceptor cells (PRC) takes place in early stages of retinal degeneration. PRCs avidly retain and display the highest content in the human body of docosahexaenoic acid (DHA; an omega-3 essential fatty acid). Docosanoids are DHA-derived mediators, such as neuroprotectin D1 (NPD1), made on-demand that promote repair, phagocytic clearance, cell survival, and are active participants of effective, well-concerted homeostasis restoration. Here we develop the concept that there is a molecular logic that sustains PRC survival and that transcriptional signatures governed by NPD1 in the RPE may be engaged.
    Advances in Experimental Medicine and Biology 10/2016; 854:385-391. DOI:10.1007/978-3-319-17121-0_51
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    ABSTRACT: More than 100 different mutations in the RPE65 gene are associated with inherited retinal degeneration. Although some missense mutations have been shown to abolish isomerase activity of RPE65, the molecular bases leading to loss of function and retinal degeneration remain incompletely understood. Here we show that several missense mutations resulted in significant decrease in expression level of RPE65 in the human retinal pigment epithelium cells. The 26S proteasome non- ATPase regulatory subunit 13, a newly identified negative regulator of RPE65, mediated degradation of mutant RPE65s, which were misfolded and formed aggregates in the cells. Many mutations, including L22P, T101I, and L408P, were mapped on nonactive sites of RPE65. Enzyme activities of these mutant RPE65s were significantly rescued at low temperature, whereas mutant RPE65s with a distinct active site mutation could not be rescued under the same conditions. 4-phenylbutyrate (PBA) displayed a significant synergistic effect on the low temperature-mediated rescue of the mutant RPE65s. Our results suggest that a low temperature eye mask and PBA, a FDA-approved oral medicine, may provide a promising “protein repair therapy” that can enhance the efficacy of gene therapy for delaying retinal degeneration caused by RPE65 mutations.
    Advances in Experimental Medicine and Biology 10/2016; 854:525-535. DOI:10.1007/978-3-319-17121-0_70
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    ABSTRACT: Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections.
    Advances in Experimental Medicine and Biology 10/2016; 854:745-750. DOI:10.1007/978-3-319-17121-0_99
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    ABSTRACT: Interest in generating human induced pluripotent stem (iPS) cells for stem cell modeling of diseases has overtaken that of patient-specific human embryonic stem cells due to the ethical, technical, and political concerns associated with the latter. In ophthalmology, researchers are currently using iPS cells to explore various applications, including: (1) modeling of retinal diseases using patient-specific iPS cells; (2) autologous transplantation of differentiated retinal cells that undergo gene correction at the iPS cell stage via gene editing tools (e.g., CRISPR/Cas9, TALENs and ZFNs); and (3) autologous transplantation of patient-specific iPSderived retinal cells treated with gene therapy. In this review, we will discuss the uses of patient-specific iPS cells for differentiating into retinal pigment epithelium (RPE) cells, uncovering disease pathophysiology, and developing new treatments such as gene therapy and cell replacement therapy via autologous transplantation.
    Advances in Experimental Medicine and Biology 10/2016; 854:549-555. DOI:10.1007/978-3-319-17121-0_73
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    ABSTRACT: Mutations in rhodopsin are one of the most common causes of retinitis pigmentosa (RP). Misfolding of rhodopsin can result in disruptions in cellular protein homeostasis, or proteostasis. There is currently no available treatment for RP. In this review, we discuss the different approaches currently being investigated for treatment of rhodopsin RP, focusing on the potential of manipulation of the proteostasis network as a therapeutic approach to combat retinal degeneration.
    Advances in Experimental Medicine and Biology 10/2016; 854:479-484. DOI:10.1007/978-3-319-17121-0_64