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https://www.readbyqxmd.com/read/27913654/novel-small-molecule-jp-153-targets-the-src-fak-paxillin-signaling-complex-to-inhibit-vegf-induced-retinal-angiogenesis
#1
Jordan J Toutounchian, Jayaprakash Pagadala, Duane D Miller, Jerome Baudry, Frank Park, Edward Chaum, Charles R Yates
Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited...
January 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/27913439/retinitis-pigmentosa-associated-cystoid-macular-oedema-pathogenesis-and-avenues-of-intervention
#2
REVIEW
S Strong, G Liew, M Michaelides
Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16-64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction...
December 2, 2016: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/27912129/incidence-of-complications-in-young-onset-diabetes-comparing-type-2-with-type-1-the-young-diab-study
#3
Anandakumar Amutha, Ranjit Mohan Anjana, Ulagamathesan Venkatesan, Harish Ranjani, Ranjit Unnikrishnan, K M Venkat Narayan, Viswanathan Mohan, Mohammed K Ali
BACKGROUND: There is little data on the incidence of diabetes complications in young onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in non European populations. METHODS: From a tertiary diabetes centre, Chennai, India, we recruited 108 T1DM (defined by abrupt onset of symptoms or diabetic ketoacidosis, absent insulin reserve requiring insulin treatment) and 90 T2DM participants (defined by absence of ketosis, good beta-cell reserve, and good response to oral agents) who were diagnosed between the ages of 10 and 25years, and without any evidence of diabetes complications at diagnosis...
November 17, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27911838/antagonists-of-growth-hormone-releasing-hormone-receptor-induce-apoptosis-specifically-in-retinoblastoma-cells
#4
Wai Kit Chu, Ka Sin Law, Sun On Chan, Jason Cheuk Sing Yam, Li Jia Chen, Hao Zhang, Herman S Cheung, Norman L Block, Andrew V Schally, Chi Pui Pang
Retinoblastoma (RB) is the most common intraocular cancer in children worldwide. Current treatments mainly involve combinations of chemotherapies, cryotherapies, and laser-based therapies. Severe or late-stage disease may require enucleation or lead to fatality. Recently, RB has been shown to arise from cone precursor cells, which have high MDM2 levels to suppress p53-mediated apoptosis. This finding leads to the hypothesis that restoring apoptosis mechanisms in RBs could specifically kill the cancer cells without affecting other retinal cells...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911769/reductive-carboxylation-is-a-major-metabolic-pathway-in-the-retinal-pigment-epithelium
#5
Jianhai Du, Aya Yanagida, Kaitlen Knight, Abbi L Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, Van Thi Bao Tran, Megan A Manson, Aravind Ramakrishnan, James B Hurley, Jennifer R Chao
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using (13)C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911706/using-induced-pluripotent-stem-cells-to-understand-retinal-ciliopathy-disease-mechanisms-and-develop-therapies
#6
REVIEW
David A Parfitt, Amelia Lane, Conor Ramsden, Katarina Jovanovic, Peter J Coffey, Alison J Hardcastle, Michael E Cheetham
The photoreceptor cells in the retina have a highly specialised sensory cilium, the outer segment (OS), which is important for detecting light. Mutations in cilia-related genes often result in retinal degeneration. The ability to reprogramme human cells into induced pluripotent stem cells and then differentiate them into a wide range of different cell types has revolutionised our ability to study human disease. To date, however, the challenge of producing fully differentiated photoreceptors in vitro has limited the application of this technology in studying retinal degeneration...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911705/disease-mechanisms-of-x-linked-retinitis-pigmentosa-due-to-rp2-and-rpgr-mutations
#7
REVIEW
Rodanthi Lyraki, Roly Megaw, Toby Hurd
Photoreceptor degeneration is the prominent characteristic of retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies resulting in blindness. Although abnormalities in many pathways can cause photoreceptor degeneration, one of the most important causes is defective protein transport through the connecting cilium, the structure that connects the biosynthetic inner segment with the photosensitive outer segment of the photoreceptors. The majority of patients with X-linked RP have mutations in the retinitis pigmentosa GTPase regulator (RPGR) or RP2 genes, the protein products of which are both components of the connecting cilium and associated with distinct mechanisms of protein delivery to the outer segment...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911427/-modern-approach-to-early-diagnosis-and-pathogenetic-treatment-of-diabetic-retinopathy
#8
I V Vorob'eva
AIM: To improve the approach to pathogenetic treatment of diabetic retinopathy (DR) through early diagnosis and a new method for predicting disease progression. MATERIAL AND METHODS: The study enrolled 330 type 2 diabetes patients with DR (660 eyes), of whom women constituted 64.6%, men - 35.4%. The mean patient age was 62.3±2.3 years. Three groups were formed: the controls - 30 healthy volunteers (60 eyes) and 30 type 2 diabetes patients without ocular involvement (DR 0, 60 eyes); group 1 - 30 type 2 diabetes patients with DR I but no diabetic macular edema (DR I without DME, 60 eyes) that were treated with calcium dobesilate; group 2 - 240 type 2 diabetes patients, who had diabetic retinopathy of different stages (DR I, II, or III with DME, 480 eyes) and received laser retinal photocoagulation (LRP)...
2016: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/27911422/-diagnostic-potential-of-optical-coherence-tomography-for-small-choroidal-melanomas
#9
A F Brovkina, A S Stoyukhina, I V Musatkina
AIM: To investigate the sequence of OCT manifestations in choroidal melanoma (CM) with account to its growth. MATERIAL AND METHODS: A total of 28 CM patients were examined. Of them, 18 patients with early CM, 10 - with medium-sized CM. The mean patient age at diagnosis was 60.54±5.31 years. Tumor location was macular (15 eyes) or perimacular (13 eyes), its prominence varied from 0.98 to 4.9 mm and basal diameter - from 5.08 to 18.9 mm. Additionally to OCT, tumor autofluorescence was studied in all cases...
2016: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/27909796/-clinical-morphological-and-molecular-biological-characteristics-of-the-aging-eye
#10
M R R Böhm, H Thomasen, F Parnitzke, K-P Steuhl
BACKGROUND: The physiological aging of the eye is associated with loss of visual function. Age-related changes of the eye can result in ophthalmological diseases. The aim of this article is to display morphological, histological and molecular biological alterations of the aging eye. MATERIAL AND METHODS: A web-based search and review of the literature for aging of the visual system including cornea, lens, vitreous humor, retina, retinal pigment epithelium (RPE), choroidea and optic nerve were carried out...
December 1, 2016: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/27908408/protective-effect-of-magnesium-acetyltaurate-against-nmda-induced-retinal-damage-involves-restoration-of-minerals-and-trace-elements-homeostasis
#11
Azliana Jusnida Ahmad Jafri, Natasha Najwa Nor Arfuzir, Lidawani Lambuk, Igor Iezhitsa, Renu Agarwal, Puneet Agarwal, Norhafiza Razali, Anna Krasilnikova, Maria Kharitonova, Vasily Demidov, Evgeny Serebryansky, Anatoly Skalny, Alexander Spasov, Ahmad Pauzi Md Yusof, Nafeeza Mohd Ismail
Glutamate-mediated excitotoxicity involving N-methyl-d-aspartate (NMDA) receptors has been recognized as a final common outcome in pathological conditions involving death of retinal ganglion cells (RGCs). Overstimulation of NMDA receptors results in influx of calcium (Ca) and sodium (Na) ions and efflux of potassium (K). NMDA receptors are blocked by magnesium (Mg). Such changes due to NMDA overstimulation are also associated with not only the altered levels of minerals but also that of trace elements and redox status...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27907042/role-of-platelet-parameters-on-neovascular-glaucoma-a-retrospective-case-control-study-in-china
#12
Shengjie Li, Wenjun Cao, Xinghuai Sun
PURPOSE: Retinal vein occlusion (RVO) and diabetic retinopathy (DR) are two major sight-threatening diseases which may lead to neovascular glaucoma (NVG). The aim of this study was to explore the association between platelet parameters and NVG. METHODS: A total of 185 subjects were enrolled for the study from January, 2012 to December, 2015 at the Eye-ENT Hospital of Fudan University. Patients include those with NVG secondary to RVO (RVO group, n = 38), patients with NVG secondary to DR (DR group, n = 47), diabetics mellitus without retinopathy (DM group, n = 52), and healthy individuals (control group, n = 48)...
2016: PloS One
https://www.readbyqxmd.com/read/27905547/in-silico-mapping-of-protein-unfolding-mutations-for-inherited-disease
#13
Caitlyn L McCafferty, Yuri V Sergeev
The effect of disease-causing missense mutations on protein folding is difficult to evaluate. To understand this relationship, we developed the unfolding mutation screen (UMS) for in silico evaluation of the severity of genetic perturbations at the atomic level of protein structure. The program takes into account the protein-unfolding curve and generates propensities using calculated free energy changes for every possible missense mutation at once. These results are presented in a series of unfolding heat maps and a colored protein 3D structure to show the residues critical to the protein folding and are available for quick reference...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904945/-sarcoidosis-and-uveitis-an-update
#14
REVIEW
J G Garweg
Ocular involvement in sarcoidosis is present in up to one third of patients and is frequently manifested before the underlying systemic disease has been diagnosed. With a view to the therapeutic consequences an early diagnosis of the underlying disease is advantageous. In cases of visual loss early diagnostic measures include invasive procedures, such as ultrasound-guided bronchoalveolar lavage and transbronchial biopsy, if nodular conjunctival or cutaneous manifestations which would confirm the diagnosis are not present...
November 30, 2016: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/27904503/stem-cell-ophthalmology-treatment-study-scots-bone-marrow-derived-stem-cells-in-the-treatment-of-leber-s-hereditary-optic-neuropathy
#15
Jeffrey N Weiss, Steven Levy, Susan C Benes
The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904478/neuro-rejuvenation-for-neuronal-function
#16
REVIEW
Yuan Liu, Richard K Lee
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell (RGC) death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904477/axon-injury-induced-endoplasmic-reticulum-stress-and-neurodegeneration
#17
REVIEW
Yang Hu
Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903733/development-of-activity-in-the-mouse-visual-cortex
#18
Jing Shen, Matthew T Colonnese
: A comprehensive developmental timeline of activity in the mouse cortex in vivo is lacking. Understanding the activity changes that accompany synapse and circuit formation is important to understand the mechanisms by which activity molds circuits and would help to identify critical checkpoints for normal development. To identify key principles of cortical activity maturation, we systematically tracked spontaneous and sensory-evoked activity with extracellular recordings of primary visual cortex (V1) in nonanesthetized mice...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27902677/perception-of-fechner-illusory-colors-in-alzheimer-disease-patients
#19
Gintaras Kaubrys, Vera Bukina, Ieva Bingelytė, Vladas Taluntis
BACKGROUND Alzheimer disease (AD) primarily affects cognition. A variety of visual disorders was established in AD. Fechner illusory colors are produced by a rotating disk with a black and white pattern. The purpose of our research was to explore the perception of illusory colors in AD. MATERIAL AND METHODS W recruited 40 AD patients (MMSE ≥14) and 40 normal controls (CG group) matched by age, education, gender in this prospective, cross-sectional, case-control study. An achromatic Benham's disk attached to a device to control the speed and direction of rotation was used to produce illusory colors...
November 30, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27902540/macular-perivenous-retinal-whitening-and-presumed-retino-ciliary-sparing-in-a-recurrent-central-retinal-vein-occlusion-associated-with-the-antiphospholipid-syndrome-and-cryoglobulinemia
#20
Dov B Sebrow, Jesse J Jung, Jason Horowitz, Jeffrey G Odel, K Bailey Freund
PURPOSE: Macular perivenous retinal whitening results from hypoperfusion-induced ischemia of the middle retina that can occur in central retinal vein occlusion (CRVO). We describe an unusual case of recurrent CRVO with macular perivenous retinal whitening and retino-ciliary venous sparing in the setting of 2 prothrombotic diseases, antiphospholipid syndrome and Type II cryoglobulinemia. METHODS: A 50-year-old man presented with intermittent loss of vision in his right eye related to a recurrent CRVO...
November 29, 2016: Retinal Cases & Brief Reports
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