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Molecular Vision

Lasse Jørgensen Cehofski, Anders Kruse, Alexander Nørgård Alsing, Jonas Ellegaard Nielsen, Shona Pedersen, Svend Kirkeby, Bent Honoré, Henrik Vorum
Purpose: To identify retinal protein changes that mediate beneficial effects of intravitreal bevacizumab in experimental branch retinal vein occlusion (BRVO). Methods: In six Danish Landrace pigs, BRVO was induced with argon laser in both eyes. After BRVO was induced, the right eye of each animal was given an intravitreal injection of bevacizumab while the left eye was treated with saline water. The retinas were collected 15 days after BRVO, and differentially expressed proteins were analyzed with tandem mass tags-based mass spectrometry...
2018: Molecular Vision
Lin Li, YeFei Wang, XiuHong Qin, Jing Zhang, ZhenZhen Zhang
Objective: To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms. Methods: Adult male Wistar rats were randomly divided into four groups: sham, sham plus ECH, I/R plus vehicle, and I/R plus ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R...
2018: Molecular Vision
Cristina García-Caballero, Burke Lieppman, Alicia Arranz-Romera, Irene T Molina-Martínez, Irene Bravo-Osuna, Michael Young, Petr Baranov, Rocío Herrero-Vanrell
Purpose: To evaluate the potential of a poly(lactic-co-glycolic acid) (PLGA)-based slow release formulation of glial cell line-derived neurotrophic factor (GDNF) alone or in combination with melatonin to rescue photoreceptors in a mouse model of retinal degeneration. Methods: GDNF and GDNF/melatonin-loaded PLGA microspheres (MSs) were prepared using a solid-in-oil-in-water emulsion solvent extraction-evaporation technique. A combination of PLGA and vitamin E (VitE) was used to create the microcarriers...
2018: Molecular Vision
Youde Jiang, Li Liu, Jena J Steinle
Purpose: Inflammation is a key component of retinal disease. We previously reported that exchange protein for cAMP 1 (Epac1) reduced inflammatory mediators, including total levels of high mobility group box 1 (HMGB1) in retinal endothelial cells (RECs) and the mouse retina. The goal of this study was to determine intermediate pathways that allow Epac1 to reduce HMGB1, which could lead to novel targets for therapeutics. Methods: We used endothelial cell-specific conditional knockout mice for Epac1 and RECs to investigate whether Epac1 requires activation of insulin like growth factor binding protein 3 (IGFBP-3) and sirtuin 1 (SIRT1) to reduce acetylated HMGB1 levels with immunoprecipitation, western blot, and enzyme-linked immunosorbent assay (ELISA)...
2018: Molecular Vision
Lisa J Hill, Ben Mead, Chloe N Thomas, Simon Foale, Elena Feinstein, Martin Berry, Richard J Blanch, Zubair Ahmed, Ann Logan
Purpose: Elevations in intraocular pressure (IOP) are associated with the development of glaucoma and loss of sight. High transforming growth factor-β (TGF-β) 1 levels in the eye's anterior chamber can lead to dysfunctional contractions through RhoA signaling in trabecular meshwork (TM) cells and IOP spikes. Sustained high TGF-β levels leads to TM fibrosis and sustained increases in IOP. We investigated whether inhibiting RhoA, using a siRNA-mediated RhoA (siRhoA), controls IOP by altering TM expression of fibrosis and contractility-related proteins in a rodent model of glaucoma...
2018: Molecular Vision
Xiaohui Zhang, Ke Xu, Bing Dong, Xiaoyan Peng, Qian Li, Feng Jiang, Yue Xie, Lu Tian, Yang Li
Purpose: Bietti crystalline dystrophy (BCD) is an autosomal recessive retinal degeneration disorder caused by mutations in CYP4V2 . The aim of this study is to describe the genetic and clinical findings in 128 unrelated Chinese patients diagnosed with BCD. Methods: Ophthalmological evaluations were performed in all patients. All coding regions of CYP4V2 were amplified and sequenced directly. Real-time quantitative PCR was performed to detect copy number variations...
2018: Molecular Vision
Zeinab Ravesh, Mahdi Dianatpour, Majid Fardaei, Maryam Taghdiri, Feyzollah Hashemi-Gorji, Vahid Reza Yassaee, Mohammad Miryounesi
Purpose: The aim of this study was to identify the molecular genetic basis of hereditary retinal dystrophies (HRDs) in five unrelated Iranian families. Methods: Whole exome sequencing and Sanger sequencing were performed in all families. Variants were analyzed using various bioinformatics databases and software. Results: Based on the selected strategies, we identified potentially causative variants in five families with HRDs: the novel homozygous deletion mutation c...
2018: Molecular Vision
Frida Jonsson, Marie Burstedt, Therese G Kellgren, Irina Golovleva
Purpose: Retinitis pigmentosa (RP) represents a large group of inherited retinal diseases characterized by clinical and genetic heterogeneity. Among patients with RP in northern Sweden, we identified two severely affected siblings and aimed to reveal a genetic cause underlying their disease. Methods: Whole exome sequencing (WES) was performed on both affected individuals. Sequence variants were filtered using a custom pipeline to find a rare or novel variant predicted to affect protein function...
2018: Molecular Vision
Sarah W Gooding, Micah A Chrenek, Salma Ferdous, John M Nickerson, Jeffrey H Boatright
Purpose: To compare methods for homogenizing the mouse whole eye or retina for RNA extraction. Methods: We tested five homogenization techniques for the whole eye and the retina. Two established shearing techniques were a version of the Potter-Elvehjem homogenizer, which uses a plastic pellet pestle in a microfuge tube, and a Dounce homogenizer. Two modern bead-beating methods used commercially manufactured devices, the Next Advance Bullet Blender and the Qiagen TissueLyser LT...
2018: Molecular Vision
Jana Kleiner, Margrit Hollborn, Peter Wiedemann, Andreas Bringmann
Purpose: Systemic hypertension is a risk factor of neovascular age-related macular degeneration; consumption of dietary salt resulting in extracellular hyperosmolarity is a main cause of hypertension. Extracellular hyperosmolarity was shown to induce expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), in RPE cells. The aim of the present study was to determine whether the hyperosmotic expression of growth factor genes in RPE cells is mediated by activator protein-1 (AP-1), and whether c-Fos and c-Jun genes are regulated by extracellular osmolarity...
2018: Molecular Vision
Zeljka Smit-McBride, Johnny Nguyen, Garrett W Elliott, Zhe Wang, Ryan A McBride, Anthony T Nguyen, Sharon L Oltjen, Glenn Yiu, Sara M Thomasy, Kent E Pinkerton, Eugene S Lee, David Cunefare, Sina Farsiu, Lawrence S Morse
Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD). Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old)...
2018: Molecular Vision
Emi Ooe, Yoshiki Kuse, Tomohiro Yako, Tetsuya Sogon, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa
Purpose: The purpose of this study was to investigate the effects of bilberry extract with its anthocyanins on retinal photoreceptor cell damage and on the endoplasmic reticulum (ER) stress induced by exposure to blue light-emitting diode (LED) light. Methods: Cultured murine photoreceptor cells (661W) were exposed to blue LED light with or without bilberry extract or its anthocyanins in the culture media. Aggregated short-wavelength opsin (S-opsin) in murine photoreceptor cells was observed with immunostaining...
2018: Molecular Vision
Takefumi Yamaguchi, Kazunari Higa, Kazuo Tsubota, Jun Shimazaki
Purpose: Primary graft failure after corneal transplantation is caused by dysfunction of corneal endothelial cells. Recently, we demonstrated that preoperative recipients' aqueous cytokine levels are associated with rapid corneal endothelial cell loss after corneal transplantation. In the present study, we evaluated the preoperative inflammatory cytokine levels in the aqueous humor (AqH) of eyes with primary graft failure following corneal transplantation. Methods: Among the prospective consecutive case series (273 eyes), this study included patients who developed primary graft failure (eight eyes) and patients who underwent corneal transplantation for the treatment of bullous keratopathy (108 eyes) or cataract surgery (30 eyes)...
2018: Molecular Vision
Alessia Fiorentino, Jing Yu, Gavin Arno, Nikolas Pontikos, Stephanie Halford, Suzanne Broadgate, Michel Michaelides, Keren J Carss, F Lucy Raymond, Michael E Cheetham, Andrew R Webster, Susan M Downes, Alison J Hardcastle
Purpose: Mutations in ARL2BP, encoding ADP-ribosylation factor-like 2 binding protein, have recently been implicated as a cause of autosomal recessive retinitis pigmentosa (arRP), with three homozygous variants identified to date. In this study, we performed next-generation sequencing to reveal additional arRP cases associated with ARL2BP variants. Methods: Whole-genome sequencing (WGS) or whole-exome sequencing (WES) was performed in 1,051 unrelated individuals recruited for the UK Inherited Retinal Disease Consortium and NIHR-BioResource Rare Diseases research studies...
2018: Molecular Vision
Christopher P Zelinka, Mailin Sotolongo-Lopez, James M Fadool
Purpose: Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness. RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1 ...
2018: Molecular Vision
Lin Zhou, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Panfeng Wang, Wenmin Sun, Fengsheng Zhang, Jiazhang Li, Tuo Li, Qingjiong Zhang
Purpose: Our previous study reported that 5.5% of probands with early-onset high myopia (eoHM) had mutations in COL2A1 or COL11A1 . Why were the probands initially considered to have eoHM but not Stickler syndrome (STL)? Methods: Probands and family members with eoHM and mutations in COL2A1 or COL11A1 were followed up and reexamined based on the criteria for STL. Further comprehensive examinations were conducted for patients with eoHM and mutations in COL2A1 or COL11A1 and controls with eoHM without mutations in COL2A1 or COL11A1 ...
2018: Molecular Vision
Jie-Ling Gong, Xiao-Tong Lou, Yu-Xiang Yuan, Li-Wen Chen, Ping-Ting Ji, Lu Li, Yin Zhao, Hong Zhang
Purpose: To investigate the relationship between intraocular pressure (IOP) and GABA receptors within the arcuate nucleus (ARC). Methods: In the chronic high IOP rat model, ibotenic acid (IBO) was injected to induce impairment of the ARC, and IOP was measured at the 0, 1, 2, 3, and 4 week time points with a Tono-Pen. To assess the expression of GABA-A/B receptors within the ARC under persistent high IOP, we performed immunofluorescence (IF) and immunohistochemical (IHC) staining at 2 weeks and 4 weeks...
2018: Molecular Vision
Mariana Vallim Salles, Fabiana Louise Motta, Renan Martin, Rafael Filippelli-Silva, Elton Dias da Silva, Patricia Varela, Kárita Antunes Costa, John PeiWen Chiang, João Bosco Pesquero, Juliana-Maria Ferraz Sallum
Purpose: The aim of this study was to analyze and report pathogenic variants in the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt disease. Methods: This retrospective study evaluated variants in the ABCA4 gene in Brazilian patients with Stargardt disease. The patients' visual acuity and age of symptom onset were obtained from previous medical records. The patients were classified according to the autofluorescence patterns. Results: Fifty patients aged between 10 and 65 years from 44 families were included in the study...
2018: Molecular Vision
Yoshiki Kuse, Kazuki Ohuchi, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa
Purpose: In mice, retinal development continues throughout the postnatal stage accompanied by the proliferation of retinal precursor cells. Previous reports showed that during the postnatal stage microglia increase from postnatal day 0 (P0) to P7. However, how microglia are associated with retinal development remains unknown. Methods: The involvement of microglia in retinal development was investigated by two approaches, microglial activation and loss, using lipopolysaccharide (LPS) and PLX3397 (pexidartinib), respectively...
2018: Molecular Vision
Margrit Hollborn, Charlotte Ackmann, Heidrun Kuhrt, Fabian Doktor, Leon Kohen, Peter Wiedemann, Andreas Bringmann
Purpose: Variants of complement factor genes, hypoxia and oxidative stress of the outer retina, and systemic hypertension affect the risk of age-related macular degeneration. Hypertension often results from the high intake of dietary salt that increases extracellular osmolarity. We determined the effects of extracellular hyperosmolarity, hypoxia, and oxidative stress on the expression of complement genes in cultured (dedifferentiated) human RPE cells and investigated the effects of C9 siRNA and C9 protein on RPE cells...
2018: Molecular Vision
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