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Amsterdam-Zuidoost, Netherlands

Veloz M.F.V.,Erasmus University Rotterdam | Zhou K.,Erasmus University Rotterdam | Lin Z.,Erasmus University Rotterdam | De Zeeuw C.I.,Erasmus University Rotterdam | And 4 more authors.
PLoS ONE | Year: 2015

The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC. © 2015 Marques et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Lapid-Gortzak R.,University of Amsterdam | Labuz G.,Rotterdam Ophthalmic Institute | Van Der Meulen I.J.,University of Amsterdam | Van Der Linden J.W.,Retina Total Eye Care | And 2 more authors.
Journal of Refractive Surgery | Year: 2015

PURPOSE: To evaluate differences in straylight between eyes implanted with a hydrophilic multifocal IOL (Seelens MF; Hanita Lenses, Hanita, Israel) and a hydrophobic multifocal IOL (SN6AD1; Alcon Laboratories, Inc., Fort Worth, TX). METHODS: In a prospective cohort study, routinely obtained straylight measurements (C-Quant; Oculus Optikgeräte, Wetzlar, Germany) 3 months after standard phacoemulsification for either cataract or refractive lens procedures were compared. Patients were implanted with either the SeeLens MF IOL or the SN6AD1 IOL. Postoperative straylight values, visual acuity, and refractive outcomes were compared. RESULTS: The SeeLens MF IOL was implanted in 84 eyes and the SN6AD1 IOL in 79 eyes. The difference in straylight was 0.08 (P = .01), with the SeeLens MF IOL having less straylight. Postoperative CDVA was logMAR -0.03 ± 0.06 in the SeeLens MF group, and logMAR -0.02 ± 0.08 in the SN6AD1 group. Mean postoperative refraction was +0.01 ± 0.43 and +0.06 ± 0.35 D, respectively. CONCLUSIONS: The Seelens MF IOL showed a straylight of log(s) 0.08 lower than the SN6AD1 IOL. In terms of spherical equivalent and visual acuity the lenses performed equally. More study will aid in understanding the causes and clinical impact of this difference. © SLACK Incorporated.

Lapid-Gortzak R.,University of Amsterdam | Van Der Meulen I.J.E.,University of Amsterdam | Van Der Linden J.W.,Retina Total Eye Care | Mourits M.P.,University of Amsterdam | Van Den Berg T.J.T.P.,Royal Dutch Academy of Arts and science
Journal of Cataract and Refractive Surgery | Year: 2014

Purpose To report the outcomes of changes in straylight before and after phacoemulsification in eyes with preoperative corrected distance visual acuity (CDVA) better than 0.1 logMAR. Setting Private refractive surgery clinic, Driebergen, the Netherlands. Design Cohort study. Methods Standard phacoemulsification with implantation of a monofocal or multifocal intraocular lens (IOL) was performed. Preoperative and 3-month postoperative straylight values, CDVA, and refractive error were compared. Results The study enrolled 160 eyes (89 patients). The mean CDVA was 0.02 ± 0.05 logMAR (range -0.1 to 0.1 logMAR) preoperatively and 0.00 ± 0.04 logMAR (range -0.1 to 0.2 logMAR) postoperatively. The mean preoperative straylight was 1.21 ± 0.20 log(s) (range 0.80 to 1.74 log[s]) and 1.11 ± 1.16 log(s) (range 0.76 to 1.63 log[s]), respectively; the improvement was statistically significant. There was a correlation between high preoperative straylight values and postoperative improvement in straylight values. Conclusions In eyes with relatively good CDVA of 0.1 logMAR or better (decimal 0.8 or better; Snellen 20/25 or better), straylight improved by 0.10 log(s) after cataract surgery. A subgroup of 44 eyes had an improvement of more than 0.20 log(s), which is comparable to a 2-line improvement on the vision chart. Financial Disclosure(s) Proprietary or commercial disclosures are listed after the references. © 2014 ASCRS and ESCRS.

Voogd J.,Erasmus University Rotterdam | Schraa-Tam C.K.L.,Erasmus University Rotterdam | Van Der Geest J.N.,Erasmus University Rotterdam | De Zeeuw C.I.,Erasmus University Rotterdam | De Zeeuw C.I.,Royal Dutch Academy of Arts and science
Cerebellum | Year: 2012

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula- nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed. ©Springer Science+Business Media, LLC 2011.

Lapid-Gortzak R.,Retina Total Eye Care | Lapid-Gortzak R.,University of Amsterdam | Van Der Meulen I.J.E.,Retina Total Eye Care | Van Der Meulen I.J.E.,University of Amsterdam | And 2 more authors.
Journal of Cataract and Refractive Surgery | Year: 2011

In a patient with complaints of photophobia and an ocular deviation, straylight was found to be increased to 1.61 (log[s]), which is 5 times the normal value. The only relative clinical finding was the edge of a too small posterior capsulotomy. Visual acuity was normal. Six weeks after the posterior capsulotomy was widened to a diameter of 6.0 mm with a neodymium:YAG laser, the symptoms were resolved and the patient was satisfied. Straylight may manifest clinically as complaints of photophobia. Straylight increase, which can be related to slitlamp findings, may lead to an interventional decision. Our clinical decision-making was also guided by straylight measurements and proved to be crucial in resolving the patient's complaints. More study of clinical situations in which straylight measurement can be used is needed. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are in the footnotes. © 2011 ASCRS and ESCRS.

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