The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Konrad Kohler - One of the best experts on this subject based on the ideXlab platform.
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photoreceptor morphology is severely affected in the β β carotene 15 15 oxygenase bcox zebrafish morphant
European Journal of Neuroscience, 2005Co-Authors: Oliver Biehlmaier, Johanna M Lampert, Johannes Von Lintig, Konrad KohlerAbstract:The retinoic acid molecule, a vitamin A derivative, is of key importance for eye and photoreceptor development in vertebrates. Several studies have provided evidence that the ventral part of the Retina is particularly susceptible to impairment in retinoid signalling during the period of its development. In zebrafish, targeted gene knockdown of beta,beta-carotene-15,15`-oxygenase (bcox), the key enzyme for vitamin A formation, provokes a loss of retinoid signalling during early eye development that results in microphthalmia at larval stages. Using this model, we analysed the consequences of this for the Retinal morphology of the fish larvae in structural details. Our analyses revealed that rods and cones do not express photoreceptor specific proteins (rhodopsin, peanut agglutinin, zpr1) in the peripheral Retina. The photoreceptors in the Central Retina showed shortened outer segments, and electron dense debris in their intermembranal space. The number of phagosomes was increased, and cell death was frequently observed in the outer nuclear layer. Furthermore, the number of Muller cells was significantly reduced in the inner nuclear layer. Thus, we found that the lack of retinoid signalling strongly effects photoreceptor development in the ventral and dorsal Retina. In addition, shortened outer segments and cell death of the remaining photoreceptors in the Central Retina indicate that there is an ongoing need for retinoid signalling for photoreceptor integrity and survival at later developmental stages.
Frank G Holz - One of the best experts on this subject based on the ideXlab platform.
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clinical and genetic characteristics of 251 consecutive patients with macular and cone cone rod dystrophy
Scientific Reports, 2018Co-Authors: Johannes Birtel, Tobias Eisenberger, Martin Gliem, Philipp L. Müller, Philipp Herrmann, Christian Betz, Diana Zahnleiter, Christine Neuhaus, Steffen Lenzner, Frank G HolzAbstract:Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with Retinal alterations solely or predominantly involving the Central Retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar Retinal phenotype, indicating a common molecular disease cause in each subgroup.
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Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
Nature Publishing Group, 2018Co-Authors: Johannes Birtel, Tobias Eisenberger, Martin Gliem, Philipp L. Müller, Philipp Herrmann, Christian Betz, Diana Zahnleiter, Christine Neuhaus, Steffen Lenzner, Frank G HolzAbstract:Abstract Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with Retinal alterations solely or predominantly involving the Central Retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar Retinal phenotype, indicating a common molecular disease cause in each subgroup
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structure function correlation of the human Central Retina
PLOS ONE, 2010Co-Authors: Peter Charbel Issa, Frank G Holz, Hendrik P N Scholl, Eric Troeger, Robert Finger, R WilkeAbstract:Background The impact of Retinal pathology detected by high-resolution imaging on vision remains largely unexplored. Therefore, the aim of the study was to achieve high-resolution structure-function correlation of the human macula in vivo. Methodology/Principal Findings To obtain high-resolution tomographic and topographic images of the macula spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO), respectively, were used. Functional mapping of the macula was obtained by using fundus-controlled microperimetry. Custom software allowed for co-registration of the fundus mapped microperimetry coordinates with both SD-OCT and cSLO datasets. The method was applied in a cross-sectional observational study of Retinal diseases and in a clinical trial investigating the effectiveness of intravitreal ranibizumab in macular telangietasia type 2. There was a significant relationship between outer Retinal thickness and Retinal sensitivity (p<0.001) and neurodegeneration leaving less than about 50 µm of parafoveal outer Retinal thickness completely abolished light sensitivity. In contrast, functional preservation was found if neurodegeneration spared the photoreceptors, but caused quite extensive disruption of the inner Retina. Longitudinal data revealed that small lesions affecting the photoreceptor layer typically precede functional detection but later cause severe loss of light sensitivity. Ranibizumab was shown to be ineffective to prevent such functional loss in macular telangietasia type 2. Conclusions/Significance Since there is a general need for efficient monitoring of the effectiveness of therapy in neurodegenerative diseases of the Retina and since SD-OCT imaging is becoming more widely available, surrogate endpoints derived from such structure-function correlation may become highly relevant in future clinical trials.
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quantification of reduced macular pigment optical density in the Central Retina in macular telangiectasia type 2
Experimental Eye Research, 2009Co-Authors: Peter Charbel Issa, Rob L P Van Der Veen, Astrid Stijfs, Frank G Holz, Hendrik P N Scholl, Tos T J M BerendschotAbstract:Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the Central Retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were investigated by fundus reflectometry and two wavelengths fundus autofluorescence (FAF; at 488 nm and 514 nm). Fundus reflectometry showed a reduced MPOD within the Central 4 degrees eccentricity that was most absent temporal to the foveola. At 6 degrees, MP density was not different from normative values. Two wavelengths FAF was in accordance with these findings. Fundus reflectometry also allowed separate determination of lutein and zeaxanthin. The patients with MacTel type 2 showed a disproportionally high zeaxanthin reduction. The study suggests that in MacTel type 2, there might be an inability to accumulate MP in the Central Retina. This disease might serve as a model to further study abnormalities of MP distribution in Retinal disorders and to elucidate the mechanisms of MP deposition in the Retina.
Samuel G Jacobson - One of the best experts on this subject based on the ideXlab platform.
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leber congenital amaurosis genotypes and Retinal structure phenotypes
Advances in Experimental Medicine and Biology, 2016Co-Authors: Samuel G Jacobson, Artur V. Cideciyan, Alexander Sumaroka, Wei Chieh Huang, Hyun Ju Nam, Rebecca Sheplock, Sharon B SchwartzAbstract:Leber congenital amaurosis (LCA) patients of 10 known genotypes (n = 24; age range, 3–25 years) were studied clinically and by optical coherence tomography (OCT). Comparisons were made between OCT results across the horizontal meridian (Central 60o) of the patients. Three patterns were identified. First, there were LCA genotypes with unusual and readily identifiable patterns, such as near normal outer nuclear layer (ONL) across the Central Retina or severely dysplastic Retina. Second, there were genotypes with well-formed foveal architecture but only residual Central islands of normal or reduced ONL thickness. Third, some genotypes showed Central ONL losses or dysmorphology suggesting early macular disease or foveal maldevelopment. Objective in vivo morphological features could complement other phenotypic characteristics and help guide genetic testing of LCA patients or at least permit a differential diagnosis of genotypes to be made in the clinic.
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normal Central Retinal function and structure preserved in retinitis pigmentosa
Investigative Ophthalmology & Visual Science, 2010Co-Authors: Samuel G Jacobson, Alexander Sumaroka, Sharon B Schwartz, Alejandro J. Roman, Tomas S Aleman, Waldo Herrera, Elizabeth A M Windsor, Lori A Atkinson, Janet D Steinberg, Artur V. CideciyanAbstract:PURPOSE To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). METHODS Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the Central Retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). RESULTS Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the Central Retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only Central islands. The Retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central Retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. CONCLUSIONS Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal Retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of Retina warrants further study.
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in vivo micropathology of best macular dystrophy with optical coherence tomography
Experimental Eye Research, 2003Co-Authors: Michael J Pianta, Artur V. Cideciyan, Edwin M. Stone, Tomas S Aleman, Janet S Sunness, Betsy Campochiaro, Peter A Campochiaro, Donald J Zack, Samuel G JacobsonAbstract:Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the Retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5-61), representing four families with known VMD2 mutations, were included. OCT scans were recorded in the Central Retina and longitudinal reflectivity profiles were analysed. The Central Retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep Retinal band termed the outer Retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory Retina, such as in Central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner Retina and Central vision.
Claire-maëlle Fovet - One of the best experts on this subject based on the ideXlab platform.
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PRIMA subRetinal wireless photovoltaic microchip implantation in non-human primate and feline models
PLoS ONE, 2020Co-Authors: Mahiul Muqit, Jean Pierre Hubschman, Jan Van Meurs, Ralf Hornig, Céline Nouvel-jaillard, Elodie Bouillet, Serge Picaud, Martin Deterre, Douglas Mccreery, Claire-maëlle FovetAbstract:PURPOSE: To evaluate the surgical technique for subRetinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy Retina underwent vitrectomy surgery and were implanted with subRetinal wireless photovoltaic microchip at the macula/Central Retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subRetinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the Central Retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into Central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subRetinal space in all 26 eyes. Intraoperative complications in primate eyes included Retinal tear, macular hole, Retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subRetinal implantation of 1.5mm and 2mm photovoltaic arrays in the Central Retina of feline and Central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials
Oliver Biehlmaier - One of the best experts on this subject based on the ideXlab platform.
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photoreceptor morphology is severely affected in the β β carotene 15 15 oxygenase bcox zebrafish morphant
European Journal of Neuroscience, 2005Co-Authors: Oliver Biehlmaier, Johanna M Lampert, Johannes Von Lintig, Konrad KohlerAbstract:The retinoic acid molecule, a vitamin A derivative, is of key importance for eye and photoreceptor development in vertebrates. Several studies have provided evidence that the ventral part of the Retina is particularly susceptible to impairment in retinoid signalling during the period of its development. In zebrafish, targeted gene knockdown of beta,beta-carotene-15,15`-oxygenase (bcox), the key enzyme for vitamin A formation, provokes a loss of retinoid signalling during early eye development that results in microphthalmia at larval stages. Using this model, we analysed the consequences of this for the Retinal morphology of the fish larvae in structural details. Our analyses revealed that rods and cones do not express photoreceptor specific proteins (rhodopsin, peanut agglutinin, zpr1) in the peripheral Retina. The photoreceptors in the Central Retina showed shortened outer segments, and electron dense debris in their intermembranal space. The number of phagosomes was increased, and cell death was frequently observed in the outer nuclear layer. Furthermore, the number of Muller cells was significantly reduced in the inner nuclear layer. Thus, we found that the lack of retinoid signalling strongly effects photoreceptor development in the ventral and dorsal Retina. In addition, shortened outer segments and cell death of the remaining photoreceptors in the Central Retina indicate that there is an ongoing need for retinoid signalling for photoreceptor integrity and survival at later developmental stages.