Science.gov

Sample records for degenerative retinal diseases

  1. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  2. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  3. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    PubMed Central

    Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

  4. Regenerative nanomedicine and the treatment of degenerative retinal diseases.

    PubMed

    Zarbin, Marco A; Montemagno, Carlo; Leary, James F; Ritch, Robert

    2012-01-01

    Regenerative medicine deals with the repair or the replacement of tissues and organs using advanced materials and methodologies. Regenerative nanomedicine uses nanoparticles containing gene transcription factors and other modulating molecules that allow reprogramming of cells in vivo as well as nanomaterials to induce selective differentiation of neural progenitor cells and to create neural-mechanical interfaces. In this article, we consider some applications of nanotechnology that may be useful for the treatment of degenerative retinal diseases, for example, use of nanoparticles for drug and gene therapy, use of nanomaterials for neural interfaces and extracellular matrix construction for cell-based therapy and neural prosthetics, and the use of bionanotechnology to re-engineer proteins and cell behavior for regenerative medicine. PMID:22170869

  5. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    PubMed

    Jeon, Sohee; Oh, Il-Hoan

    2015-04-01

    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. PMID:25560700

  6. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients. PMID:23857173

  7. Histone Deacetylases Inhibitors in the Treatment of Retinal Degenerative Diseases: Overview and Perspectives

    PubMed Central

    Dai, Xufeng; Du, Wei; Pang, Ji-jing

    2015-01-01

    Retinal degenerative diseases are one of the important refractory ophthalmic diseases, featured with apoptosis of photoreceptor cells. Histone acetylation and deacetylation can regulate chromosome assembly, gene transcription, and posttranslational modification, which are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. The histone deacetylase inhibitors (HDACis) have the ability to cause hyperacetylation of histone and nonhistone proteins, resulting in a variety of effects on cell proliferation, differentiation, anti-inflammation, and anti-apoptosis. Several HDACis have been approved for clinical trials to treat cancer. Studies have shown that HDACis have neuroprotective effects in nervous system damage. In this paper, we will summarize the neuroprotective effects of common HDACis in retinal degenerative diseases and make a prospect to the applications of HDACis in the treatment of retinal degenerative diseases in the future. PMID:26137316

  8. Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

    PubMed Central

    Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

    2016-01-01

    Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

  9. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    PubMed Central

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  10. Restoration of synaptic function in sight for degenerative retinal disease.

    PubMed

    Schubert, Timm; Wissinger, Bernd

    2015-07-01

    Synaptic disorganization is a prominent feature of many neurological diseases of the CNS, including Parkinson's disease, intellectual development disorders, and autism. Although synaptic plasticity is critical for learning and memory, it is unclear whether this innate property helps restore synaptic function in disease once the primary cause of disease is abrogated. An answer to this question may come from a recent investigation in X-linked retinoschisis, a currently untreatable retinopathy. In this issue of the JCI, Ou, Vijayasarathy, and colleagues showed progressive disorganization of key functional elements of the synapse between photoreceptors and ON-bipolar cells in a retinoschisin-deficient mouse model. Moreover, they demonstrated that adeno-associated virus-mediated (AAV-mediated) delivery of the retinoschisin gene restores structure and function to the photoreceptor to ON-bipolar cell synapse in mouse models, even in adults at advanced stages of the disease. The results of this study hold promise that AAV-based supplemental gene therapy will benefit patients with X-linked retinoschisis in a forthcoming clinical trial. PMID:26098210

  11. Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse.

    PubMed

    Gupta, Vivek K; Chitranshi, Nitin; Gupta, Veer B; Golzan, Mojtaba; Dheer, Yogita; Wall, Roshana Vander; Georgevsky, Dana; King, Anna E; Vickers, James C; Chung, Roger; Graham, Stuart

    2016-06-01

    The APP-PS1ΔE9 mouse model of Alzheimer's disease (AD) exhibits age dependent amyloid β (Aβ) plaque formation in their central nervous system due to high expression of mutated human APP and PSEN1 transgenes. Here we evaluated Aβ deposition and changes in soluble Aβ accumulation in the retinas of aged APP-PS1 mice using a combination of immunofluorescence, retinal flat mounts and western blotting techniques. Aβ accumulation in the retina has previously been shown to be associated with retinal ganglion cell apoptosis in animal models of glaucoma. This study investigated changes in the inner retinal function and structure in APP-PS1 mice using electrophysiology and histological approaches respectively. We report for the first time a significant decline in scotopic threshold response (STR) amplitudes which represents inner retinal function in transgenic animals compared to the wild type counterparts (p<0.0001). Thinning of the retina particularly involving inner retinal layers and reduction in axonal density in the optic nerve was also observed. TUNEL staining was performed to examine neuronal apoptosis in the inner retina. Intraocular pressure (IOP) measurements showed that APP-PS1ΔE9 mice had a slightly elevated IOP, but the significance of this finding is not yet known. Together, these results substantiate previous observations and highlight that APP-PS1ΔE9 mice show evidence of molecular, functional and morphological degenerative changes in the inner retina. PMID:27133194

  12. Signaling Networks of Retinal Ganglion Cell Formation and the Potential Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases.

    PubMed

    Wu, Nan; Wang, Yi; Yang, Lanbo; Cho, Kin-Sang

    2016-08-01

    Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases. PMID:27466076

  13. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  14. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  15. Nanofiber Scaffold-Based Tissue-Engineered Retinal Pigment Epithelium to Treat Degenerative Eye Diseases.

    PubMed

    Hotaling, Nathan A; Khristov, Vladimir; Wan, Qin; Sharma, Ruchi; Jha, Balendu Shekhar; Lotfi, Mostafa; Maminishkis, Arvydas; Simon, Carl G; Bharti, Kapil

    2016-06-01

    Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturers that are capable of producing the nanofiber scaffolds in such a way that would be biologically, regulatory, clinically, and commercially viable. Then, a discussion of how the scaffolds could be characterized, both morphologically and mechanically, to develop a testing process that is viable for regulatory screening is performed. Finally, an example of a tissue-engineered RPE/scaffold construct is given to provide the reader a framework for understanding how these pieces could fit together to develop a tissue-engineered RPE/scaffold construct that could pass regulatory scrutiny and can be commercially successful. PMID:27110730

  16. Biosynthesis, Characterization, and Efficacy in Retinal Degenerative Diseases of Lens Epithelium-derived Growth Factor Fragment (LEDGF1–326), a Novel Therapeutic Protein*

    PubMed Central

    Baid, Rinku; Upadhyay, Arun K.; Shinohara, Toshimichi; Kompella, Uday B.

    2013-01-01

    For vision-threatening retinitis pigmentosa and dry age-related macular degeneration, there are no United States Food and Drug Administration (FDA)-approved treatments. We identified, biosynthesized, purified, and characterized lens epithelium-derived growth factor fragment (LEDGF1–326) as a novel protein therapeutic. LEDGF1–326 was produced at about 20 mg/liter of culture when expressed in the Escherichia coli system, with about 95% purity and aggregate-free homogeneous population with a mean hydrodynamic diameter of 9 ± 1 nm. The free energy of unfolding of LEDGF1–326 was 3.3 ± 0.5 kcal mol−1, and melting temperature was 44.8 ± 0.2 °C. LEDGF1–326 increased human retinal pigment epithelial cell viability from 48.3 ± 5.6 to 119.3 ± 21.1% in the presence of P23H mutant rhodopsin-mediated aggregation stress. LEDGF1–326 also increased retinal pigment epithelial cell FluoSphere uptake to 140 ± 10%. Eight weeks after single intravitreal injection in Royal College of Surgeons (RCS) rats, LEDGF1–326 increased the b-wave amplitude significantly from 9.4 ± 4.6 to 57.6 ± 8.8 μV for scotopic electroretinogram and from 10.9 ± 5.6 to 45.8 ± 15.2 μV for photopic electroretinogram. LEDGF1–326 significantly increased the retinal outer nuclear layer thickness from 6.34 ± 1.6 to 11.7 ± 0.7 μm. LEDGF1–326 is a potential new therapeutic agent for treating retinal degenerative diseases. PMID:23640891

  17. My Retina Tracker™: An On-line International Registry for People Affected with Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives - A New Resource.

    PubMed

    Fisher, Joan K; Bromley, Russell L; Mansfield, Brian C

    2016-01-01

    My Retina Tracker™ is a new on-line registry for people affected with inherited orphan retinal degenerative diseases, and their unaffected, genetic relatives. Created and supported by the Foundation Fighting Blindness, it is an international resource designed to capture the disease from the perspective of the registry participant and their retinal health care providers. The registry operates under an Institutional Review Board (IRB)-approved protocol and allows sharing of de-identified data with participants, researchers and clinicians. All participants sign an informed consent that includes selecting which data they wish to share. There is no minimum age of participation. Guardians must sign on behalf of minors, and children between the ages of 12 to 17 also sign an informed assent. Participants may compare their disease to others in the registry using graphical interpretations of the aggregate registry data. Researchers and clinicians have two levels of access. The first provides an interface to interrogate all data fields registrants have agreed to share based on their answers in the IRB informed consent. The second provides a route to contact people in the registry who may be eligible for studies or trials, through the Foundation. PMID:26427418

  18. Genetic pediatric retinal diseases

    PubMed Central

    Say, Emil Anthony T.

    2014-01-01

    Hereditary pediatric retinal diseases are a diverse group of disorders with pathologies affecting different cellular structures or retinal development. Many can mimic typical pediatric retinal disease such as retinopathy of prematurity, vitreous hemorrhage, retinal detachment and cystoid macular edema. Multisystem involvement is frequently seen in hereditary pediatric retinal disease. A thorough history coupled with a good physical examination can oftentimes lead the ophthalmologist or pediatrician to the correct genetic test and correct diagnosis. In some instances, evaluation of parents or siblings may be required to determine familial involvement when the history is inconclusive or insufficient and clinical suspicion is high.

  19. Systems Pharmacology Links GPCRs with Retinal Degenerative Disorders

    PubMed Central

    Chen, Yu; Palczewski, Krzysztof

    2015-01-01

    In most biological systems, second messengers and their key regulatory and effector proteins form links between multiple cellular signaling pathways. Such signaling nodes can integrate the deleterious effects of genetic aberrations, environmental stressors, or both in complex diseases, leading to cell death by various mechanisms. Here we present a systems (network) pharmacology approach that, together with transcriptomics analyses, was used to identify different G protein–coupled receptors that experimentally protected against cellular stress and death caused by linked signaling mechanisms. We describe the application of this concept to degenerative and diabetic retinopathies in appropriate mouse models as an example. Systems pharmacology also provides an attractive framework for devising strategies to combat complex diseases by using (repurposing) US Food and Drug Administration–approved pharmacological agents. PMID:25839098

  20. [Therapeutical effect of growth-associated protein 43 (GAP43) gene-modified bone marrow mesenchymal stem cell transplantation on rat retinal degenerative diseases].

    PubMed

    Yang, Juan; Xie, Maosong; Zheng, Weidong; Hu, Jianzhang; Qu, Qiang

    2016-08-01

    Objective To investigate the potential of the treatment of growth-associated protein 43 (GAP43) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) for retinitis pigmentosa (RP). Methods BMSCs were isolated and cultured by adherence method. By transfecting GAP43 gene into BMSCs via a lentivirus vector, we got GAP43 gene-modified BMSCs. Sixty-three Royal College of Surgeons (RCS) rats were randomly divided into three groups: experimental group, negative control group and blank control group. The experimental rats received subretinal injection of GAP43 gene-modified BMSCs. The negative control rats received subretinal injection of BMSCs. The control rats received subretinal injection of PBS. Thirty days after transplanting, the retinal thickness was detected by optical coherence tomography (OCT), and the expression of rhodopsin in RCS rat retinas was examined by Western blotting. Results Compared with the blank control group and the negative control group, 30 days after GAP43 gene-modified BMSC transplantation, the retinal thickness of the experimental group remarkably increased and the expression of rhodopsin significantly rose. Conclusion GAP43 gene-modified BMSC transplantation can increase survival photoreceptor cells and delay retinal degeneration. PMID:27412933

  1. Bowman lecture on the role of inflammation in degenerative disease of the eye

    PubMed Central

    Forrester, J V

    2013-01-01

    Inflammation, in the pathogenesis of many diseases previously thought to be strictly genetic, degenerative, metabolic, or endocrinologic in aetiology, has gradually entered the framework of a general mechanism of disease. This is exemplified by conditions such as Parkinson's disease, Alzheimer's disease, atherosclerosis, diabetes, and the more recently described Metabolic Syndrome. Chronic inflammatory processes have a significant, if not primary role, in ophthalmic diseases, particularly in retinal degenerative diseases. However, inflammation itself is not easy to define, and some aspects of inflammation may be beneficial, in a process described as ‘para-inflammation' by Medhzitov. In contrast, the damaging effects of inflammation, mediated by pro-inflammatory macrophages through activation of the intracellular protein-signalling complexes, termed inflammasomes, are well recognised and are important therapeutic targets. In this review, the range of inflammatory processes in the eye is evaluated in the context of how these processes impact upon retinal degenerative disease, particularly diabetic retinopathy and age-related macular degeneration. PMID:23288138

  2. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers. PMID:27486355

  3. Degenerative diseases of the vertebral column.

    PubMed

    Resnick, D

    1985-07-01

    Several distinct degenerative processes affect the articulations of the vertebral column; each is associated with characteristic radiographic and pathologic abnormalities, and many are accompanied by significant clinical manifestations. A discussion of these processes is best accomplished according to the type of joint that is involved. With regard to cartilaginous articulations, of which the intervertebral disk is most important, intervertebral (osteo)chondrosis, spondylosis deformans, and, in the cervical spine, uncovertebral arthrosis are the major degenerative disorders. Osteoarthritis (osteoarthrosis) affects any of the synovium-lined joints of the vertebral column, including the apophyseal, costovertebral, transitional lumbosacral, median atlantoaxial, and sacroiliac articulations. Fibrous articulations, ligaments, or entheses (sites of tendon or ligament attachment to bone) are involved in diffuse idiopathic skeletal hyperostosis, ossification of the posterior spinal ligaments, and Baastrup disease. Of the many complications of these degenerative processes, alignment abnormalities (including segmental instability, degenerative spondylolisthesis, senile kyphosis, and degenerative scoliosis), intervertebral disk displacement, calcification or ossification, and spinal stenosis are the most important. PMID:3923556

  4. Is running associated with degenerative joint disease

    SciTech Connect

    Panush, R.S.; Schmidt, C.; Caldwell, J.R.; Edwards, N.L.; Longley, S.; Yonker, R.; Webster, E.; Nauman, J.; Stork, J.; Pettersson, H.

    1986-03-07

    Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. The authors compared the prevalence of degenerative joint disease among 17 male runners with 18 male nonrunners. Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. They did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest that long-duration, high-mileage running need to be associated with premature degenerative joint disease in the lower extremities.

  5. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  6. MR imaging of degenerative disc disease.

    PubMed

    Farshad-Amacker, Nadja A; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav

    2015-09-01

    Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided. PMID:26094867

  7. MRI Evaluation of Lumbar Disc Degenerative Disease

    PubMed Central

    Patel, Rupal; Mehta, Chetan; Patel, Narrotam

    2015-01-01

    Introduction: Lower back pain secondary to degenerative disc disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 y. MRI is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast and precise localization of intervertebral discs changes. Aims and Objective: To evaluate the characterization, extent, and changes associated with the degenerative lumbar disc disease by Magnetic Resonance Imaging. Study Design: Cross-sectional and observational study. Materials and Methods: A total 109 patients of the lumbar disc degeneration with age group between 17 to 80 y were diagnosed & studied on 1.5 Tesla Magnetic Resonance Imaging machine. MRI findings like lumbar lordosis, Schmorl’s nodes, decreased disc height, disc annular tear, disc herniation, disc bulge, disc protrusion and disc extrusion were observed. Narrowing of the spinal canal, lateral recess and neural foramen with compression of nerve roots observed. Ligamentum flavum thickening and facetal arthropathy was observed. Result: Males were more commonly affected in Degenerative Spinal Disease & most of the patients show loss of lumbar lordosis. Decreased disc height was common at L5-S1 level. More than one disc involvement was seen per person. L4 – L5 disc was the most commonly involved. Annular disc tear, disc herniation, disc extrusion, narrowing of spinal canal, narrowing of lateral recess, compression of neural foramen, ligamentum flavum thickening and facetal arthropathy was common at the L4 –L5 disc level. Disc buldge was common at L3 – L4 & L4 – L5 disc level. Posterior osteophytes are common at L3 - L4 & L5 –S1 disc level. L1- L2 disc involvement and spondylolisthesis are less common. Conclusion: Lumbar disc degeneration is the most common cause of low back pain. Plain radiograph can be helpful in visualizing gross anatomic changes in

  8. Degenerative disease of the lumbar spine.

    PubMed

    Kovacs, F M; Arana, E

    2016-04-01

    In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures. PMID:26872873

  9. cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness.

    PubMed

    Wiley, Luke A; Burnight, Erin R; DeLuca, Adam P; Anfinson, Kristin R; Cranston, Cathryn M; Kaalberg, Emily E; Penticoff, Jessica A; Affatigato, Louisa M; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2016-01-01

    Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

  10. cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

    PubMed Central

    Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

    2016-01-01

    Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

  11. Operative Management of Lumbar Degenerative Disc Disease.

    PubMed

    Lee, Yu Chao; Zotti, Mario Giuseppe Tedesco; Osti, Orso Lorenzo

    2016-08-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  12. Operative Management of Lumbar Degenerative Disc Disease

    PubMed Central

    Lee, Yu Chao; Osti, Orso Lorenzo

    2016-01-01

    Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term. PMID:27559465

  13. [Etiology, pathophysiology and conservative therapy of degenerative rheumatic diseases].

    PubMed

    Jandrić, Slavica

    2002-01-01

    ETIOLOGY OF DEGENERATIVE JOINT DISEASES: Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors, inflammation and other risk factors contribute to development of osteoarthrosis. PATHOPHYSIOLOGY OF DEGENERATIVE JOINT DISEASES: Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical, radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. TREATMENT OF DEGENERATIVE JOINT DISEASES: Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy. PMID:12037935

  14. Anabolic factors in degenerative joint disease.

    PubMed

    Sandell, L J

    2007-02-01

    While a great deal of information is available on the cellular and molecular biology of cartilage degradation, less is known about anabolism in normal cartilage and degenerating cartilage. A consistent amount of evidence is now available on the neo-synthesis of matrix molecules and enzymes in OA: the entire cell metabolism appears to be increased leading to the hypothesis that chondrocytes in OA are actually "activated". This chapter will focus on anabolic events that are now known to occur in articular cartilage. We will begin to view articular cartilage as a complex three-dimensional tissue in which local events may be different. We will also be interested in viewing the development of degenerative arthritis as a continuum from functionally normal tissue to degeneration. PMID:17305513

  15. Anterior Cervical Spine Surgery for Degenerative Disease: A Review

    PubMed Central

    SUGAWARA, Taku

    Anterior cervical spine surgery is an established surgical intervention for cervical degenerative disease and high success rate with excellent long-term outcomes have been reported. However, indications of surgical procedures for certain conditions are still controversial and severe complications to cause neurological dysfunction or deaths may occur. This review is focused mainly on five widely performed procedures by anterior approach for cervical degenerative disease; anterior cervical discectomy, anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical foraminotomy, and arthroplasty. Indications, procedures, outcomes, and complications of these surgeries are discussed. PMID:26119899

  16. Color Doppler imaging of retinal diseases.

    PubMed

    Dimitrova, Galina; Kato, Satoshi

    2010-01-01

    Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting. PMID:20385332

  17. Gene Therapy for Retinal Diseases

    PubMed Central

    Samiy, Nasrollah

    2014-01-01

    Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

  18. Immune Mechanisms in Inflammatory and Degenerative Eye Disease

    PubMed Central

    Perez, Victor L.; Caspi, Rachel R.

    2015-01-01

    It has recently been recognized that pathology of age-associated degenerative eye diseases such as adult macular degeneration (AMD), glaucoma and diabetic retinopathy, have strong immunological underpinnings. Attempts have been made to extrapolate to age-related degenerative disease insights from inflammatory processes associated with non-infectious uveitis, but these have not yet been sufficiently informative. Here we review recent findings on the immune processes underlying uveitis and those that have been shown to contribute to AMD, discussing in this context parallels and differences between overt inflammation and para-inflammation in the eye. We propose that mechanisms associated with ocular immune privilege, in combination with paucity of age-related antigen(s) within the target tissue, dampen what could otherwise be overt inflammation and result in the para-inflammation that characterizes age-associated neurodegenerative disease. PMID:25981967

  19. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases.

    PubMed

    Orsini, Marco; Nascimento, Osvaldo J M; Matta, Andre P C; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S; Filho, Pedro F Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-04-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome - among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson's disease, Alzheimer's disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  20. Revisiting the Term Neuroprotection in Chronic and Degenerative Diseases

    PubMed Central

    Orsini, Marco; Nascimento, Osvaldo J.M.; Matta, Andre P.C.; Reis, Carlos Henrique Melo; de Souza, Olivia Gameiro; Bastos, Victor Hugo; Moreira, Rayele; Ribeiro, Pedro; Fiorelli, Stenio; Novellino, Pietro; Pessoa, Bruno; Cunha, Mariana; Pupe, Camila; Morales, Pedro S.; Filho, Pedro F. Moreira; Trajano, Eduardo Lima; Oliveira, Acary Bulle

    2016-01-01

    Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome – among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson’s disease, Alzheimer’s disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this neuroprotective effect. PMID:27127599

  1. Vitiligo: A Possible Model of Degenerative Diseases

    PubMed Central

    Bellei, Barbara; Pitisci, Angela; Ottaviani, Monica; Ludovici, Matteo; Cota, Carlo; Luzi, Fabiola; Dell'Anna, Maria Lucia; Picardo, Mauro

    2013-01-01

    Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects. PMID:23555779

  2. Health assessment of environmental pollutants; Proliferative and degenerative diseases

    SciTech Connect

    Stuart, B.O. )

    1987-01-01

    The health assessments of environmental air contaminants are at present frequently based upon probability of cancer, if this has been identified as a potential result of prolonged exposure to the particular inhalation hazard. However, for many airborne hazards chronic inhalation exposure may result in morbidity or mortality risks due to chronic degenerative diseases such as emphysema, fibrosis, or chronic obstructive pulmonary disease that may be nearly as great or greater than those of more widely recognized neoplastic or proliferative disease. The relative hazards of environmentally released radioactive and chemical air contaminants, i.e., radon daughters and diesel engine exhaust, are discussed as examples.

  3. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  4. Total Disc Arthroplasty for Treating Lumbar Degenerative Disc Disease

    PubMed Central

    2015-01-01

    Study Design Lumber disc arthroplasty is a technological advancement that has occurred in the last decade to treat lumbar degenerative disk diseases. Purpose The aim of this retrospective study was to establish the impact and outcomes of managing patients with lumbar degenerative disk disease who have been treated with lumbar total disc arthroplasty (TDA). Overview of Literature Several studies have shown promising results following this surgery. Methods We reviewed the files of 104 patients at the Department of Neurosurgery in Colmar (France) who had been operated on by lumbar spine arthroplasty (Prodisc) between April 2002 and October 2008. Results Among the 104 patients, 67 were female and 37 were male with an average age of 33.1 years. We followed the cases for a mean of 20 months. The most frequent level of discopathy was L4-L5 with 62 patients (59.6%) followed by L5-S1 level with 52 patients (50%). Eighty-three patients suffered from low back pain, 21 of which were associated with radiculopathy. The status of 82 patients improved after surgery according to the Oswestry Disability Index score, and 92 patients returned to work. Conclusions The results indicate that TDA is a good alternative treatment for lumbar spine disk disease, particularly for patients with disabling and chronic low back pain. This technique contributes to improve living conditions with correct patient selection for surgery. PMID:25705336

  5. Oxidants, antioxidants, and the degenerative diseases of aging.

    PubMed Central

    Ames, B N; Shigenaga, M K; Hagen, T M

    1993-01-01

    Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great. Images Fig. 1 PMID:8367443

  6. Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

    PubMed Central

    Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

    2015-01-01

    Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

  7. Role of Oxidative RNA Damage in Chronic-Degenerative Diseases

    PubMed Central

    2015-01-01

    Normal cellular metabolism and exposure to ionizing and ultraviolet radiations and exogenous agents produce reactive oxygen species (ROS). Due to their reactivity, they can interact with many critical biomolecules and induce cell damage. The reaction of ROS with free nucleobases, nucleosides, nucleotides, or oligonucleotides can generate numerous distinct modifications in nucleic acids. Oxidative damage to DNA has been widely investigated and is strongly implicated in the development of many chronic-degenerative diseases. In contrast, RNA damage is a poorly examined field in biomedical research. In this review, I discuss the importance of RNA as a target of oxidative damage and the role of oxidative damage to RNA in the pathogenesis of some chronic-degenerative diseases, such as neurological disorders, atherosclerosis, and cancer. Furthermore, I review recent evidence suggesting that RNA may be the target for toxic agents and indicating RNA degradation as a powerful tool to treat any pathology in which there is an aberrant expression of mRNA and/or its gene products. PMID:26078805

  8. Total Disc Replacement in Lumbar Degenerative Disc Diseases

    PubMed Central

    2015-01-01

    More than 10 years have passed since lumbar total disc replacement (LTDR) was introduced for the first time to the world market for the surgical management of lumbar degenerative disc disease (DDD). It seems like the right time to sum up the relevant results in order to understand where LTDR stands on now, and is heading forward to. The pathogenesis of DDD has been currently settled, but diagnosis and managements are still controversial. Fusion is recognized as golden standard of surgical managements but has various kinds of shortcomings. Lately, LTDR has been expected to replace fusion surgery. A great deal of LTDR reports has come out. Among them, more than 5-year follow-up prospective randomized controlled studies including USA IDE trials were expected to elucidate whether for LTDR to have therapeutic benefit compared to fusion. The results of these studies revealed that LTDR was not inferior to fusion. Most of clinical studies dealing with LTDR revealed that there was no strong evidence for preventive effect of LTDR against symptomatic degenerative changes of adjacent segment disease. LTDR does not have shortcomings associated with fusion. However, it has a potentiality of the new complications to occur, which surgeons have never experienced in fusion surgeries. Consequently, longer follow-up should be necessary as yet to confirm the maintenance of improved surgical outcome and to observe any very late complications. LTDR still may get a chance to establish itself as a substitute of fusion both nominally and virtually if it eases the concerns listed above. PMID:26713139

  9. Retinal Macroglial Responses in Health and Disease

    PubMed Central

    de Hoz, Rosa; Rojas, Blanca; Ramírez, Ana I.; Salazar, Juan J.; Gallego, Beatriz I.; Triviño, Alberto; Ramírez, José M.

    2016-01-01

    Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies. PMID:27294114

  10. Complement, a target for therapy in inflammatory and degenerative diseases.

    PubMed

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies. PMID:26493766

  11. [Novel mechanism for retinal vascular diseases].

    PubMed

    Suzuma, Kiyoshi

    2015-03-01

    I. A new therapeutic target for diabetic retinopathy. Recent reports state that succinate may be an independent retinal angiogenic factor. We evaluated concentrations in vitreous from proliferative diabetic retinopathy (PDR), and found that succinate increased significantly in PDR. Interestingly, levels of succinate from bevacizumab-pre-injected PDR were normal, suggesting that vascular endothelial growth factor (VEGF) had a positive feedback mechanism for succinate since succinate was previously reported to induce VEGF. II. A new understanding of central retinal vein occlusion (CRVO). We evaluated retinal blood flow velocity with laser speckle flowgraphy (LSFG) made in Japan, and found that cases in which both macular edema and retinal blood flow velocity improved after anti-VEGF therapy had better prognosis. In ischemic CRVO at final visit, mean retinal blood velocity was less than 50% of fellow eyes after 1st anti-VEGF therapy, suggesting that those cases might have poor prognosis. LSFG is useful for evaluation and decision in CRVO treatment. III. From exploration for mechanism in retinal vascular diseases to re-vascularization therapy. The standard treatment for retinal non-perfusion area is scatter laser photocoagulation, which is both invasive of the peripheral retina and may prove destructive. Re-vascularization is an ideal strategy for treatment of retinal non-perfusion area. To develop a new methods for re-vascularization in retinal non-perfusion area, we have designed experiments using a retina without vasculature differentiated from induced pluripotent stem(iPS) cells. PMID:25854111

  12. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

  13. Optical Coherence Tomography Angiography in Retinal Diseases

    PubMed Central

    Chalam, K. V.; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  14. Optical Coherence Tomography Angiography in Retinal Diseases.

    PubMed

    Chalam, K V; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  15. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer's disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer's patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer's patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a "window" to the brain. PMID:27551275

  16. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  17. Retinal microvascular network attenuation in Alzheimer's disease

    PubMed Central

    Williams, Michael A.; McGowan, Amy J.; Cardwell, Chris R.; Cheung, Carol Y.; Craig, David; Passmore, Peter; Silvestri, Giuliana; Maxwell, Alexander P.; McKay, Gareth J.

    2015-01-01

    Introduction Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. Methods Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. Results Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97]) were more likely to have AD after appropriate adjustment. Discussion Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD. PMID:26634224

  18. Quantitative Fundus Autofluorescence for the Evaluation of Retinal Diseases.

    PubMed

    Armenti, Stephen T; Greenberg, Jonathan P; Smith, R Theodore

    2016-01-01

    The retinal pigment epithelium (RPE) is juxtaposed to the overlying sensory retina, and supports the function of the visual system. Among the tasks performed by the RPE are phagocytosis and processing of outer photoreceptor segments through lysosome-derived organelles. These degradation products, stored and referred to as lipofuscin granules, are composed partially of bisretinoids, which have broad fluorescence absorption and emission spectra that can be detected clinically as fundus autofluorescence with confocal scanning laser ophthalmoscopy (cSLO). Lipofuscin accumulation is associated with increasing age, but is also found in various patterns in both acquired and inherited degenerative diseases of the retina. Thus, studying its pattern of accumulation and correlating such patterns with changes in the overlying sensory retina are essential to understanding the pathophysiology and progression of retinal disease. Here, we describe a technique employed by our lab and others that uses cSLO in order to quantify the level of RPE lipofuscin in both healthy and diseased eyes. PMID:27023389

  19. Stem cell treatment of degenerative eye disease☆

    PubMed Central

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A.H.; Leadbeater, Wendy; Scheven, Ben A.

    2015-01-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. PMID:25752437

  20. A Degenerative Retinal Process in HIV-Associated Non-Infectious Retinopathy

    PubMed Central

    Freeman, William R.; Sprague, L. James; Gomez, Maria Laura; Cheng, Lingyun; El-Emam, Sharif; Mojana, Francesca; Bartsch, Dirk-Uwe; Bosten, Jenny; Ayyagari, Radha; Hardiman, Gary

    2013-01-01

    HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner–retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV

  1. Nanoengineering of therapeutics for retinal vascular disease.

    PubMed

    Gahlaut, Nivriti; Suarez, Sandra; Uddin, Md Imam; Gordon, Andrew Y; Evans, Stephanie M; Jayagopal, Ashwath

    2015-09-01

    Retinal vascular diseases, including diabetic retinopathy, neovascular age related macular degeneration, and retinal vein occlusion, are leading causes of blindness in the Western world. These diseases share several common disease mechanisms, including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation, which provide opportunities for common therapeutic strategies. Treatment of these diseases using laser therapy, anti-VEGF injections, and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying root causes of pathology, and may have deleterious side effects. Furthermore, many patients continue to progress toward legal blindness despite receiving regular therapy. Nanomedicine, the engineering of therapeutics at the 1-100 nm scale, is a promising approach for improving clinical management of retinal vascular diseases. Nanomedicine-based technologies have the potential to revolutionize the treatment of ophthalmology, through enabling sustained release of drugs over several months, reducing side effects due to specific targeting of dysfunctional cells, and interfacing with currently "undruggable" targets. We will discuss emerging nanomedicine-based applications for the treatment of complications associated with retinal vascular diseases, including angiogenesis and inflammation. PMID:26022642

  2. Regenerative therapies for equine degenerative joint disease: a preliminary study.

    PubMed

    Broeckx, Sarah; Zimmerman, Marieke; Crocetti, Sara; Suls, Marc; Mariën, Tom; Ferguson, Stephen J; Chiers, Koen; Duchateau, Luc; Franco-Obregón, Alfredo; Wuertz, Karin; Spaas, Jan H

    2014-01-01

    Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC) II and p63, low in MHC I and positive for Ki67, collagen type II (Col II) and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP) as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced) MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment. PMID:24465787

  3. [Pathobiochemistry of joint destruction in inflammatory and degenerative joint diseases].

    PubMed

    Greiling, H; Kleesiek, K; Reinards, R

    1987-08-01

    While the biochemical mechanism which leads to the destruction of joints in the course of degenerative and inflammatory arthropathies has not been cleared up completely to this day, basic differences have been noted in the way the two types of arthropathy affect the articular cartilage. The differences are described from the viewpoint of pathobiochemistry as they are fundamental to causal therapy. PMID:3314203

  4. [Role of defective intracellular proteolysis in human degenerative diseases].

    PubMed

    Nezelof, Christian

    2012-11-01

    the nature of proteolysis. In this article, therefore, the following distinction should be made:--Lysosomal failures. They represent hereditary metabolic disorders involving all categories of cells. They are characterized by the accumulation of homogeneous material related to the underlying disease. Young people are predominantly affected--UPS failures. They represent sporadic conditions principally involving long-lived cells. The accumulated material is heterogeneous, composed of abnormal proteins and various "garbage-like" waste, including pigments. The elderly are predominatly affected, suggesting an epigenetic wear and tear process. Hypothetically, most the sporadic neurodegenerative diseases, from retinal macular degeneration and its associated drüsen to Alzheimer's disease, Parkinson's disease may represent fairly good examples of the UPS deficit. PMID:24313014

  5. Connexin43 in retinal injury and disease.

    PubMed

    Danesh-Meyer, Helen V; Zhang, Jie; Acosta, Monica L; Rupenthal, Ilva D; Green, Colin R

    2016-03-01

    Gap junctions are specialized cell-to-cell contacts that allow the direct transfer of small molecules between cells. A single gap junction channel consists of two hemichannels, or connexons, each of which is composed of six connexin protein subunits. Connexin43 is the most ubiquitously expressed isoform of the connexin family and in the retina it is prevalent in astrocytes, Müller cells, microglia, retinal pigment epithelium and endothelial cells. Prior to docking with a neighboring cell, Connexin43 hemichannels have a low open probability as open channels constitute a large, relatively non-specific membrane pore. However, with injury and disease Connexin43 upregulation and hemichannel opening has been implicated in all aspects of secondary damage, especially glial cell activation, edema and loss of vascular integrity, leading to neuronal death. We here review gap junctions and their roles in the retina, and then focus in on Connexin43 gap junction channels in injury and disease. In particular, the effect of pathological opening of gap junction hemichannels is described, and hemichannel mediated loss of vascular integrity explained. This latter phenomenon underlies retinal pigment epithelium loss and is a common feature in several retinal diseases. Finally, Connexin43 channel roles in a number of retinal diseases including macular degeneration, glaucoma and diabetic retinopathy are considered, along with results from related animal models. A final section describes gap junction channel modulation and the ocular delivery of potential therapeutic molecules. PMID:26432657

  6. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  7. Detection of degenerative disease of the temporomandibular joint by bone scintigraphy: concise communication

    SciTech Connect

    Goldstein, H.A.; Bloom, C.Y.

    1980-10-01

    Nine patients with facial pain were evaluated with limited bone scans. The scintigrams correlated with microscopy in all patients, although radiographs correlated with microscopy in only five patients. The degenerative disease process in the temporomandibular joint was more extensive in the patients with radiographic and scintigraphic abnormalities than in those with scintigraphic abnormalities alone. The limited bone scan appears useful in detecting early degenerative changes in the temporomandibular joint.

  8. Nanocarriers of nanotechnology in retinal diseases.

    PubMed

    Al-Halafi, Ali M

    2014-10-01

    We are approaching a new era of retinal pharmacotherapy where new drugs are rapidly being worked out for the treatment of posterior-segment disease. Recent development in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising excellent approach for advanced therapy of ocular diseases. The primary goal is to develop a variety of drug delivery systems to complement and further enhance the efficacy of the available new medications. The ideal sustained release technology will provide a high level of safety with continuous release over an extended period of time while maintaining almost total drug bioactivity. The use of nanocarriers, such as cyclodextrin nanoparticle suspension, liposomes, nanospheres and, nanoemulsions for gene therapy of retinal diseases has been highlighted in this review. PMID:25473348

  9. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

    PubMed Central

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-01-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H+-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson’s disease, Huntington’s disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  10. Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.

    PubMed

    Zhou, Ren-Peng; Wu, Xiao-Shan; Wang, Zhi-Sen; Xie, Ya-Ya; Ge, Jin-Fang; Chen, Fei-Hu

    2016-08-01

    Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson's disease, Huntington's disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases. PMID:27493834

  11. Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

    PubMed Central

    Gamm, David M.; Wang, Shaomei; Lu, Bin; Girman, Sergei; Holmes, Toby; Bischoff, Nicholas; Shearer, Rebecca L.; Sauvé, Yves; Capowski, Elizabeth; Svendsen, Clive N.; Lund, Raymond D.

    2007-01-01

    Background A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. Methodology/Principal Findings Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. Conclusions/Significance Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest

  12. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    PubMed

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. PMID:27384734

  13. Retinitis Pigmentosa

    MedlinePlus

    ... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... available? Are there any related diseases? What is retinitis pigmentosa? Retinitis pigmentosa (RP) refers to a group of ...

  14. Retinal arterial occlusive disease in systemic lupus erythematosus.

    PubMed

    Gold, D; Feiner, L; Henkind, P

    1977-09-01

    Four patients with systemic lupus erythematosus (SLE) developed an unusual form of occlusive retinal arterial disease. The most prominent clinical features of this disorder were deposition of yellow-white material in retinal arterial walls and evidence of multifocal retinal arterial occlusion. Fluorescein angiographic findings included nonperfusion of the obstructed arteries and the retinal capillary beds fed by them, and fluorescein leakage at the sites of involvement of the retinal arteries. This ocular complication of SLE is presumably a manifestation of the widespread systemic vascular problems seen in this disorder. It may be more common in patients with lupus involving the CNS. PMID:901267

  15. In Vivo Molecular Imaging in Retinal Disease

    PubMed Central

    Xie, Fang; Luo, Wenting; Zhang, Zhongyu; Sun, Dawei

    2012-01-01

    There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of ocular fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule upregulation, some novel imaging agents that target retinal endothelial molecules were generated. In vivo molecular imaging has a great potential to impact medicine by detecting diseases or screening disease in early stages, identifying extent of disease, selecting disease and patient-specific therapeutic treatment, applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:22363836

  16. Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients.

    PubMed

    Eser, O; Eser, B; Cosar, M; Erdogan, M O; Aslan, A; Yıldız, H; Solak, M; Haktanır, A

    2011-01-01

    We investigated a possible association between aggrecan gene polymorphism and lumbar degenerative disc disease in Turkish patients. One hundred 20-30-year-old patients with or without low back pain were selected for the study. Lumbar magnetic resonance imaging was performed on all patients. The patient group had low back pain clinically and degenerative disc disease radiographically. The control group included patients with and without low back pain: all were negative radiographically for degenerative disc disease. Genomic DNA was extracted from all participants. A PCR assay were used to evaluate variable number of tandem repeat polymorphism of aggrecan gene alleles to determine if there was any correlation with degenerative disc disease. Significant associations were found between short repeated alleles of the aggrecan gene and severe disc degeneration. A significant association was also found between short repeated alleles of the aggrecan gene and multilevel disc herniation as well as extrusion and sequestration types of disc herniation. In Turkish population, short repeated alleles of the aggrecan gene are associated with increased disc degeneration and disc herniation. PMID:21948754

  17. Motor training in degenerative spinocerebellar disease: ataxia-specific improvements by intensive physiotherapy and exergames.

    PubMed

    Synofzik, Matthis; Ilg, Winfried

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames ("exergames"). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  18. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    PubMed Central

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  19. Insights into neurogenesis and aging: potential therapy for degenerative disease?

    PubMed Central

    Marr, Robert A; Thomas, Rosanne M; Peterson, Daniel A

    2010-01-01

    Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age. PMID:20806052

  20. Efficacy of a Human Amniotic Tissue-derived Allograft, NuCel, in Patients Undergoing Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    ClinicalTrials.gov

    2016-03-28

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  1. Transcorneal Electrical Stimulation Therapy for Retinal Disease

    ClinicalTrials.gov

    2012-05-03

    Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

  2. Retinal vascular regeneration.

    PubMed

    Otani, Atsushi; Friedlander, Martin

    2005-01-01

    We discuss the potential use of stem cells for therapeutic angiogenesis in the treatment of retinal diseases. We demonstrate that the clinical utility of these EPC may be not limited in the treatment of ischemic retinal diseases but may also have application for the treatment of retinal degenerative disorders and for a form of cell-based gene therapy. One of the greatest potential benefits of bone marrow derived EPC therapy is the possible use of autologous grafts. Nonetheless, potential toxicities and unregulated cell growth will need to be carefully evaluated before this approach is brought to the clinics. PMID:15804843

  3. [Childhood feeding, chronic-degenerative disease in adults, and nutrigenomics].

    PubMed

    Caramia, G

    2007-01-01

    Significant advances have been made in understanding the relation between dietary factors and disease prevention. However, the identification of those who will or will not benefit from dietary intervention strategies remains a major obstacle. The execution of the Human Genome Project has brought forth a wealth of information about the structure of the genome and the spectacular development of broad genomics technologies have catalyzed a new era in both medicine and nutrition. Each person is genetically unique and phenotypically distinct, and the genetic makeup that individuals inherit from their ancestors is responsible for variation in responses to food. Evidence continues to implicate dietary components and genetic susceptibilities as important determinants of chronic diseases, cancer risk and tumor behavior. Variation in incidence among and within populations with similar dietary patterns suggests that an individual's response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenetics studies the genetic basis of the different individual responses to the same nutritional stimulus and Nutrigenomics is defined as the interaction between nutrition and an individual's genome. With the application of "omic" technologies, proteomic, metabolomic, transcriptomic, will increase our fundamental knowledge of the interaction between life processes and diet. The identification of diet-gene interactions will offers an opportunity to develop dietary interventions that will lead to evidence-based dietary strategies for restoring health and fitness, obviate the effects of genetic factors for preventing diet-related diseases and provide important clues about gene expression and gene modulation by environmental factors. PMID:18410060

  4. [Whiplash injury of the cervical spine--on the role of pre-existing degenerative diseases].

    PubMed

    Meenen, N M; Katzer, A; Dihlmann, S W; Held, S; Fyfe, I; Jungbluth, K H

    1994-06-01

    Radiological investigations contribute little in differentiating the problems of patients with whiplash injuries. Nevertheless the more prolonged cases of whiplash injuries must not be attributed to preexisting degenerative disease, despite radiologically-proven medicolegal opinion. In this study, 60 patients who were seen for whiplash injuries in the Department for Trauma and Reconstructive Surgery at the University Hospital Hamburg-Eppendorf for clinical and radiological evaluation, an average of 5.7 years post injury, were divided into two groups (n = 30) depending on radiologically-proven preexisting degenerative changes of the cervical spine. On average the patients with degenerative changes were 11.2 years older than those with healthy vertebral columns and also demonstrated an increase in acute symptoms in the lower cervical spine (cervicobrachial syndrome). The chronicity of individual symptoms such as neck-pain, dizziness, nausea and psychological illness was also observed in both groups. Problems such as paresthesias as well as pain in the shoulder-arm-area appeared to increase in subsequent check-ups, irrespective of the earlier degenerative changes. Patients with typical posterior headaches recovered faster when they had radiologically normal spines. Presenting late, there was a significant accumulation of patients with pre-existing degenerative changes complaining merely of tinnitus. The earlier changes in any individual motion segment do not determine the clinical course of whiplash injuries, but merely represent an area of increased vulnerability to trauma. On the other hand, trauma has not been proven to influence the development or aggravation of degenerative changes in normal or diseased spines. We are not able to differentiate the posttraumatic course from the natural history of the degenerative process, either clinically or radiologically. Considering the involvement of sensitive neurological structures the classical objective organic diagnosis

  5. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    PubMed

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system: PMID:26255528

  6. Retinal fundus imaging in mouse models of retinal diseases.

    PubMed

    Alex, Anne F; Heiduschka, Peter; Eter, Nicole

    2013-01-01

    The development of in vivo retinal fundus imaging in mice has opened a new research horizon, not only in ophthalmic research. The ability to monitor the dynamics of vascular and cellular changes in pathological conditions, such as neovascularization or degeneration, longitudinally without the need to sacrifice the mouse, permits longer observation periods in the same animal. With the application of the high-resolution confocal scanning laser ophthalmoscopy in experimental mouse models, access to a large spectrum of imaging modalities in vivo is provided. PMID:23150359

  7. Oxygen-ozone therapy for degenerative spine disease in the elderly: a prospective study.

    PubMed

    Bonetti, Matteo; Fontana, Alessandro; Martinelli, Francesco; Andreula, Cosma

    2011-01-01

    We describe our experience of oxygen-ozone therapy to treat degenerative spine disease in the elderly. From April 2004 to March 2008 we selected 129 patients with CT and/or MR evidence of spondyloarthrosis and disc degeneration of the lumbar spine. All patients enrolled in the study had contraindications to the administration of commonly used analgesic and anti-inflammatory drugs.Oxygen-ozone therapy was given by CT-guided intraforaminal injection as the first treatment followed by 4 weekly paralumbar infiltrations on an outpatient basis. The full treatment lasted a month. Clinical outcome was assessed 3 months and 1 year after treatment. The good results obtained indicate that oxygen-ozone therapy is an ideal treatment with no side-effects in elderly patients with degenerative spine disease. PMID:21107950

  8. Neuroimaging and Genetic Risk for Alzheimer’s Disease and Addiction-Related Degenerative Brain Disorders

    PubMed Central

    Jahanshad, Neda; Leonardo, Cassandra D.; Thompson, Paul M.

    2014-01-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer’s disease (AD). Here we describe how multimodal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer’s disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear. PMID:24142306

  9. Lumbar Degenerative Disc Disease: Current and Future Concepts of Diagnosis and Management

    PubMed Central

    Taher, Fadi; Essig, David; Lebl, Darren R.; Hughes, Alexander P.; Sama, Andrew A.; Cammisa, Frank P.; Girardi, Federico P.

    2012-01-01

    Low back pain as a result of degenerative disc disease imparts a large socioeconomic impact on the health care system. Traditional concepts for treatment of lumbar disc degeneration have aimed at symptomatic relief by limiting motion in the lumbar spine, but novel treatment strategies involving stem cells, growth factors, and gene therapy have the theoretical potential to prevent, slow, or even reverse disc degeneration. Understanding the pathophysiological basis of disc degeneration is essential for the development of treatment strategies that target the underlying mechanisms of disc degeneration rather than the downstream symptom of pain. Such strategies ideally aim to induce disc regeneration or to replace the degenerated disc. However, at present, treatment options for degenerative disc disease remain suboptimal, and development and outcomes of novel treatment options currently have to be considered unpredictable. PMID:22567411

  10. Treatment of multilevel degenerative disc disease with intradiscal electrothermal therapy.

    PubMed

    Malik, K

    2007-04-01

    Intradiscal electrothermal therapy is a frequently performed procedure for the pain of internal disc disruption. It is typically performed on one to two discs; the discal treatment is followed by a long period of rest and rehabilitation. In patients with multilevel disc disease, intradiscal electrothermal therapy is either not contemplated or only one to two discs are treated at a time. This approach therefore either denies these patients the potential benefits of intradiscal electrothermal therapy or significantly prolongs the period of pain and disability. A 25-year-old female patient presented with internal disc disruption at four lumbar disc levels, diagnosed by provocative discography and post discography CT scan. All these discs were treated simultaneously by intradiscal electrothermal therapy. The patient tolerated the procedure well and responded favourably with significant and prolonged decrease in her symptoms. She reported sustained reduction in her pain and showed no clinical evidence of early neurological or infectious complications during 18 months of follow-up. This report indicates that intradiscal electrothermal therapy can be performed at multiple levels at a single sitting, compared to intradiscal electrothermal therapy performed at one to two discs at a time, this approach may obviate the need for surgery and may reduce the duration of pain and disability incurred. However, the influence of multilevel intradiscal electrothermal therapy on long-term complications or outcome is not known. PMID:17444324

  11. Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease.

    PubMed

    Kokona, Despina; Georgiou, Panagiota-Christina; Kounenidakis, Mihalis; Kiagiadaki, Foteini; Thermos, Kyriaki

    2016-01-01

    The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease. PMID:26881135

  12. Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease

    PubMed Central

    Kokona, Despina; Georgiou, Panagiota-Christina; Kounenidakis, Mihalis; Kiagiadaki, Foteini; Thermos, Kyriaki

    2016-01-01

    The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease. PMID:26881135

  13. Optical coherence tomography (OCT) in hereditary retinal degenerations: Layer-by-layer analyses in normal and diseased retinas

    NASA Astrophysics Data System (ADS)

    Huang, Yijun

    OCT is a new technique for non-invasive, non-contact, cross-sectional imaging of biological tissues with micrometer longitudinal resolution. As it applies to the field of ophthalmology, OCT can delineate retinal sublayers based on their backscattering characteristics, and permit quantitative measurement of the structure of retina in vivo. This dissertation intended to clarify the basis of the OCT signals and whether this procedure has potential for diagnosis and monitoring of human retinal degenerative diseases. Key to this goal are quantitation of OCT signal features and accurate, layer-by-layer correlation of these features with underlying retinal microanatomy. In normal and degenerate avian and swine retinas, OCT signal features were quantified using custom computer programs, and were correlated with cryosections of unfixed retinas obtained at the same retinal location. The results suggested a definable and quantifiable relationship between OCT signal components and retinal microanatomy. The correlation in the outer retina indicated that the OCT posterior highly reflective band, or the outer- retina-choroid complex (ORCC), is attributable to the photoreceptor layer, RPE, and anterior choroid. Further evidence of OCT signal origin was provided by the rd chicken and the rhodopsin P347L mutant transgenic swine. In these animals where photoreceptors had degenerated, OCT abnormalities were observed at the level of and vitreal to the ORCC, consistent with the hypothesis that photoreceptors contribute to the ORCC. Studies of quantitative OCT analysis in man were also performed. In selected hereditary retinal degenerative diseases in which there was regional difference in retinal function, frequently observed OCT abnormalities that were associated with visual dysfunction were reduced OCT thickness, reduced ORCC thickness, increased reflectivity posterior to ORCC, and abnormal OCT signal lamination. These preliminary results suggested that OCT abnormalities at the level

  14. Disparities in Rates of Spine Surgery for Degenerative Spine Disease Between HIV Infected and Uninfected Veterans

    PubMed Central

    King, Joseph T.; Gordon, Adam J.; Perkal, Melissa F.; Crystal, Stephen; Rosenthal, Ronnie A.; Rodriguez-Barradas, Maria C.; Butt, Adeel A.; Gibert, Cynthia L.; Rimland, David; Simberkoff, Michael S.; Justice, Amy C.

    2011-01-01

    Study Design Retrospective analysis of nationwide Veterans Health Administration (VA) clinical and administrative data. Objective Examine the association between HIV infection and the rate of spine surgery for degenerative spine disease. Summary of Background Data Combination anti-retroviral therapy (cART) has prolonged survival in patients with HIV/AIDS, increasing the prevalence of chronic conditions such as degenerative spine disease that may require spine surgery. Methods We studied all HIV infected patients under care in the VA from 1996–2008 (n=40,038) and uninfected comparator patients (n=79,039) matched on age, gender, race, year, and geographic region. The primary outcome was spine surgery for degenerative spine disease defined by ICD-9 procedure and diagnosis codes. We used a multivariate Poisson regression to model spine surgery rates by HIV infection status, adjusting for factors that might affect suitability for surgery (demographics, year, comorbidities, body mass index, cART, and laboratory values). Results Two-hundred twenty eight HIV infected and 784 uninfected patients underwent spine surgery for degenerative spine disease during 700,731 patient-years of follow-up (1.44 surgeries per 1,000 patient-years). The most common procedures were spinal decompression (50%), and decompression and fusion (33%); the most common surgical sites were the lumbosacral (50%), and cervical (40%) spine. Adjusted rates of surgery were lower for HIV infected patients (0.86 per 1,000 patient-years of follow-up) than for uninfected patients (1.41 per 1,000 patient-years; IRR 0.61, 95% CI: 0.51, 0.74, P<0.001). Among HIV infected patients, there was a trend towards lower rates of spine surgery in patients with detectable viral loads levels (IRR 0.76, 95% CI: 0.55, 1.05, P=0.099). Conclusion In the VA, HIV infected patients experience significantly reduced rates of surgery for degenerative spine disease. Possible explanations include disease prevalence, emphasis on

  15. Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

    2015-01-01

    Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

  16. Relationship between retinal vascular occlusions and incident cerebrovascular diseases

    PubMed Central

    Zhou, Yue; Zhu, Wengen; Wang, Changyun

    2016-01-01

    Abstract Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD. We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software. A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21–3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24–1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12–3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03–1.48; P = 0.04) were significantly associated with increased risk of CVD. Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  17. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells in retinal disease.

    PubMed

    Feigl, Beatrix; Zele, Andrew J

    2014-08-01

    Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are a class of photoreceptors with established roles in non-image-forming processes. Their contributions to image-forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. Intrinsically photosensitive retinal ganglion cells can be divided into five ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioral marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma, and hereditary optic neuropathy. We briefly review the anatomical distributions, projections, and basic physiological mechanisms of ipRGCs and their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the PLR can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction. PMID:24879087

  18. Psychological and Educational Recommendations for Working with Young People with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Chacón-López, Helena; López-Justicia, Maria D.; Vervloed, Mathijs P. J.

    2014-01-01

    This article reviews the consequences of Retinitis Pigmentosa, a retinal degenerative disease with progressive reduction of the visual field, visual acuity, contrast sensitivity, and night blindness. Retinitis Pigmentosa is addressed from both a psychological and an educational standpoint, focusing on the impact on learning, emotional well-being,…

  19. Picking a bone with WISP1 (CCN4): new strategies against degenerative joint disease

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    As the world’s population continues to age, it is estimated that degenerative joint disease disorders such as osteoarthritis will impact at least 130 million individuals throughout the globe by the year 2050. Advanced age, obesity, genetics, gender, bone density, trauma, and a poor level of physical activity can lead to the onset and progression of osteoarthritis. However, factors that lead to degenerative joint disease and involve gender, genetics, epigenetic mechanisms, and advanced age are not within the control of an individual. Furthermore, current therapies including pain management, improved nutrition, and regular programs for exercise do not lead to the resolution of osteoarthritis. As a result, new avenues for targeting the treatment of osteoarthritis are desperately needed. Wnt1 inducible signaling pathway protein 1 (WISP1), a matricellular protein and a downstream target of the wingless pathway Wnt1, is one such target to consider that governs cellular protection, stem cell proliferation, and tissue regeneration in a number of disorders including bone degeneration. However, increased WISP1 expression also has been associated with the progression of osteoarthritis. WISP1 has an intricate relationship with a number of proliferative and protective pathways that include phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin -6 (IL-6), transforming growth factor-β, matrix metalloproteinase, small non-coding ribonucleic acids (RNAs), sirtuin silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and the mechanistic target of rapamycin (mTOR). Taken together, this complex association WISP1 holds with these signaling pathways necessitates a fine biological regulation of WISP1 activity that can offset the progression of degenerative joint disease, but not limit the cellular protective capabilities of the WISP1 pathway. PMID:26893943

  20. Comparison of the Dynesys Dynamic Stabilization System and Posterior Lumbar Interbody Fusion for Lumbar Degenerative Disease

    PubMed Central

    Zhang, Yang; Shan, Jian-Lin; Liu, Xiu-Mei; Li, Fang; Guan, Kai; Sun, Tian-Sheng

    2016-01-01

    Background There have been few studies comparing the clinical and radiographic outcomes between the Dynesys dynamic stabilization system and posterior lumbar interbody fusion (PLIF). The objective of this study is to compare the clinical and radiographic outcomes of Dynesys and PLIF for lumbar degenerative disease. Methods Of 96 patients with lumbar degenerative disease included in this retrospectively analysis, 46 were treated with the Dynesys system and 50 underwent PLIF from July 2008 to March 2011. Clinical and radiographic outcomes were evaluated. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD). Results The mean follow-up time in the Dynesys group was 53.6 ± 5.3 months, while that in the PLIF group was 55.2 ± 6.8 months. At the final follow-up, the Oswestry disability index and visual analogue scale score were significantly improved in both groups. The range of motion (ROM) of stabilized segments in Dynesys group decreased from 7.1 ± 2.2° to 4.9 ± 2.2° (P < 0.05), while that of in PLIF group decreased from 7.3 ± 2.3° to 0° (P < 0.05). The ROM of the upper segments increased significantly in both groups at the final follow-up, the ROM was higher in the PLIF group. There were significantly more radiographic ASDs in the PLIF group than in the Dynesys group. The incidence of complications was comparable between groups. Conclusions Both Dynesys and PLIF can improve the clinical outcomes for lumbar degenerative disease. Compared to PLIF, Dynesys stabilization partially preserves the ROM of the stabilized segments, limits hypermobility in the upper adjacent segment, and may prevent the occurrence of ASD. PMID:26824851

  1. Role of the Retinal Vascular Endothelial Cell in Ocular Disease

    PubMed Central

    Bharadwaj, Arpita S.; Appukuttan, Binoy; Wilmarth, Phillip A.; Pan, Yuzhen; Stempel, Andrew J.; Chipps, Timothy J.; Benedetti, Eric E.; Zamora, David O.; Choi, Dongseok; David, Larry L.; Smith, Justine R.

    2012-01-01

    Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell. PMID:22982179

  2. Retinal area detector from scanning laser ophthalmoscope (SLO) images for diagnosing retinal diseases.

    PubMed

    Haleem, Muhammad Salman; Han, Liangxiu; van Hemert, Jano; Li, Baihua; Fleming, Alan

    2015-07-01

    Scanning laser ophthalmoscopes (SLOs) can be used for early detection of retinal diseases. With the advent of latest screening technology, the advantage of using SLO is its wide field of view, which can image a large part of the retina for better diagnosis of the retinal diseases. On the other hand, during the imaging process, artefacts such as eyelashes and eyelids are also imaged along with the retinal area. This brings a big challenge on how to exclude these artefacts. In this paper, we propose a novel approach to automatically extract out true retinal area from an SLO image based on image processing and machine learning approaches. To reduce the complexity of image processing tasks and provide a convenient primitive image pattern, we have grouped pixels into different regions based on the regional size and compactness, called superpixels. The framework then calculates image based features reflecting textural and structural information and classifies between retinal area and artefacts. The experimental evaluation results have shown good performance with an overall accuracy of 92%. PMID:25167560

  3. Preliminary results of automated removal of degenerative joint disease in bone scan lesion segmentation

    NASA Astrophysics Data System (ADS)

    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Auerbach, Martin; Goldin, Jonathan; Henkel, Keith; Banola, Ashley; Morris, Darren; Coy, Heidi; Brown, Matthew S.

    2013-03-01

    Whole-body bone scintigraphy (or bone scan) is a highly sensitive method for visualizing bone metastases and is the accepted standard imaging modality for detection of metastases and assessment of treatment outcomes. The development of a quantitative biomarker using computer-aided detection on bone scans for treatment response assessment may have a significant impact on the evaluation of novel oncologic drugs directed at bone metastases. One of the challenges to lesion segmentation on bone scans is the non-specificity of the radiotracer, manifesting as high activity related to non-malignant processes like degenerative joint disease, sinuses, kidneys, thyroid and bladder. In this paper, we developed an automated bone scan lesion segmentation method that implements intensity normalization, a two-threshold model, and automated detection and removal of areas consistent with non-malignant processes from the segmentation. The two-threshold model serves to account for outlier bone scans with elevated and diffuse intensity distributions. Parameters to remove degenerative joint disease were trained using a multi-start Nelder-Mead simplex optimization scheme. The segmentation reference standard was constructed manually by a panel of physicians. We compared the performance of the proposed method against a previously published method. The results of a two-fold cross validation show that the overlap ratio improved in 67.0% of scans, with an average improvement of 5.1% points.

  4. [Prediction of outcomes of surgical treatment of degenerative lumbar disk disease].

    PubMed

    Zhuravlev, Iu I; Nazarenko, G I; Cherkashov, A M; Riazanov, V V; Nazarenko, A G

    2009-01-01

    The paper focuses on algorithms of outcomes assessment of surgical treatment of the patients with degenerative lumbar disk disease. From 1997 to 2006 389 patients with discogenic lumbar pain were operated in the Medical Center of Central Bank of Russia. 185 patients underwent radiofrequency destruction of facet nerves, laser percutaneous lumbar discectomy was performed in 39 patients, microdiscectomy -- in 131, and decompression combined with lumbar spine stabilization -- in 31 cases. Clinical and radiological data of each patient were recorded in the database using 3-point scale according to intensity of the feature. Assessment of patients' condition was performed pre- and postoperatively (after discharge and after 6, 12 and 24 months interval). Postoperative outcome was recorded for the current period in compliance with modified criteria of Kawabata et al. Obtained data were mathematically and statistically processed. Developed algorithms allowed assessment of postoperative outcome in the patients with degenerative lumbar disk disease. Outcome data can be used for evaluation of feasibility of surgical treatment as well as for selection of surgical technique. PMID:19505029

  5. Compounded pimobendan for canine chronic degenerative mitral valve disease and pulmonary hypertension.

    PubMed

    Helms, Scott R; Fox, Samantha; Mixon, William; Vail, Jane

    2012-01-01

    Pimobendan (Vetmedin) is an effective treatment for canine chronic degenerative mitral valve disease and dilated cardiomyopathy. In an off-label use, it may also be of benefit for the treatment of pulmonary hypertension in dogs. In this report, we describe the effects of a palatable customized oral form of pimobendan used with both compounded and commercially manufactured conventional drug therapy to treat degenerative mitral valve disease and pulmonary hypertension in two small dogs. For those patients, who resisted many types of oral medication, the standard manufactured dose of pimobendan was inappropriate. Formulations of the preparations used to treat the patients described in this report are provided for easy reference. It should be noted that at the time of this writing, Boehringer Ingelheim GmbH (Ingelheim am Rhein, Germany), the manufacturer of pimobendan, has expressed concern about the stability of that agent in aqueous compounded form. To our knowledge, no current data confirming the stability or bioequivalence of compounded pimobendan exist. PMID:23050309

  6. Central Retinal Vein Occlusion in a Patient with Retinal Vasculitis and Crohn's Disease

    PubMed Central

    Figueiredo, Lígia; Rothwell, Renata; Brandão, Arnaldo

    2014-01-01

    The authors report a rare case of a 47-year-old woman with Crohn's disease (CD) who presented with retinal vasculitis and central retinal vein occlusion (CRVO) during remission. The patient complained of sudden painless visual loss in her left eye (OS). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/20 in the right eye and hand movements in OS. Ophthalmoscopy and fluorescein angiography of OS showed signs of nonischemic CRVO and extensive vasculitis. She was treated with oral prednisolone, mercaptopurine, and intravitreal bevacizumab in OS. After 1 month of treatment, VA of OS improved to 5/10 and after 1 year it was 10/10 with complete resolution of retinal vasculitis and nonischemic CRVO. PMID:25506451

  7. A Qualitative Self-Study of Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Fourie, Robert James

    2007-01-01

    Retinitis Pigmentosa (RP) is a retinal degenerative disease causing progressive blindness. Most research on RP is biomedical, and mostly from an observer perspective, therefore poorly reflecting the lived experience of having RP. Accordingly, the researcher conducted a retrospective qualitative self-study, to analyze reflections on his own…

  8. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    PubMed Central

    Welling, John D; Tarabishy, Ahmad B; Christoforidis, John B

    2012-01-01

    Cytomegalovirus (CMV) retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants. PMID:22570539

  9. Pregnancy-associated retinal diseases and their management.

    PubMed

    Errera, Marie-Hélène; Kohly, Radha P; da Cruz, Lyndon

    2013-01-01

    Pregnancy-associated retinal diseases are conditions that may occur uniquely in pregnancy or, more commonly, general conditions that may worsen or alter during pregnancy as a result of hematologic, hormonal, metabolic, cardiovascular, and immunologic changes. Diabetic retinopathy (DR) is by far the most common retinal condition that is altered by pregnancy. However, there are currently no widely accepted, precise clinical guidelines regarding its management during pregnancy. At present it is not possible to predict who will regress and who will progress without treatment. Some of the variation in progression of DR in pregnancy may be a result of well-known risk factors such as hypertension or inadequate glycemic control prior to pregnancy. Other pregnancy-associated retinal diseases are relatively uncommon, and their treatments are poorly characterized. Pre-existing conditions include the white dot syndromes, such as punctuate inner choroidopathy and ocular histoplasmosis syndrome, as well as chorioretinal neovascularization from many other etiologies. Retinal and chorioretinal disorders that can arise during pregnancy include central serous chorioretinopathy and occlusive vasculopathy such as retinal artery occlusion (Purtschers-like retinopathy) and retinal vein occlusion. There remains a small group that appear to be unique to pregnancy, with pre-eclampsia- and eclampsia-associated retinopathy, disseminated intravascular coagulopathy, or amniotic fluid embolism being the best described. In angiogenic retinal diseases outside of pregnancy, the use of anti-vascular endothelial growth factor (anti-VEGF agents) has proven helpful. There are no safety data about the use of anti-VEGF agents during pregnancy, and conventionally the proposed interventions have been laser photocoagulation and systemic or intravitreal injections of steroids. Most of the literature on the treatment of pregnancy associated-chorioretinal neovascularization is anecdotal. PMID:23410822

  10. Radiological and Radionuclide Imaging of Degenerative Disease of the Facet Joints.

    PubMed

    Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath

    2015-01-01

    The facet joint has been increasingly implicated as a potential source of lower back pain. Diagnosis can be challenging as there is not a direct correlation between facet joint disease and clinical or radiological features. The purpose of this article is to review the diagnosis, treatment, and current imaging modality options in the context of degenerative facet joint disease. We describe each modality in turn with a pictorial review using current evidence. Newer hybrid imaging techniques such as single photon emission computed tomography/computed tomography (SPECT/CT) provide additional information relative to the historic gold standard magnetic resonance imaging. The diagnostic benefits of SPECT/CT include precise localization and characterization of spinal lesions and improved diagnosis for lower back pain. It may have a role in selecting patients for local therapeutic injections, as well as guiding their location with increased precision. PMID:26170560

  11. Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

    NASA Astrophysics Data System (ADS)

    Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

    2015-03-01

    Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

  12. Radiological and Radionuclide Imaging of Degenerative Disease of the Facet Joints

    PubMed Central

    Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath

    2015-01-01

    The facet joint has been increasingly implicated as a potential source of lower back pain. Diagnosis can be challenging as there is not a direct correlation between facet joint disease and clinical or radiological features. The purpose of this article is to review the diagnosis, treatment, and current imaging modality options in the context of degenerative facet joint disease. We describe each modality in turn with a pictorial review using current evidence. Newer hybrid imaging techniques such as single photon emission computed tomography/computed tomography (SPECT/CT) provide additional information relative to the historic gold standard magnetic resonance imaging. The diagnostic benefits of SPECT/CT include precise localization and characterization of spinal lesions and improved diagnosis for lower back pain. It may have a role in selecting patients for local therapeutic injections, as well as guiding their location with increased precision. PMID:26170560

  13. Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease

    PubMed Central

    Berger, Peter; Zenzmaier, Christoph

    2014-01-01

    Degenerative fibrotic diseases encompass numerous systemic and organ-specific disorders. Despite their associated significant morbidity and mortality, there is currently no effective antifibrotic treatment. Fibrosis is characterized by the development and persistence of myofibroblasts, whose unregulated deposition of extracellular matrix components disrupts signaling cascades and normal tissue architecture leading to organ failure and death. The profibrotic cytokine transforming growth factor beta (TGFβ) is considered the foremost inducer of fibrosis, driving myofibroblast differentiation in diverse tissues. This review summarizes recent in vitro and in vivo data demonstrating that TGFβ-induced myofibroblast differentiation is driven by a prooxidant shift in redox homeostasis. Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. Moreover, complex interplay between NOX4-derived H2O2 and NO signaling regulates myofibroblast differentiation. Restoring redox homeostasis via antioxidants or NOX4 inactivation as well as by enhancing NO signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases can inhibit and reverse myofibroblast differentiation. Thus, dysregulated redox signaling represents a potential therapeutic target for the treatment of wide variety of different degenerative fibrotic disorders. PMID:24701562

  14. Developing retinal biomarkers of neurological disease: an analytical perspective

    PubMed Central

    MacCormick, Ian JC; Czanner, Gabriela; Faragher, Brian

    2015-01-01

    The inaccessibility of the brain poses a problem for neuroscience. Scientists have traditionally responded by developing biomarkers for brain physiology and disease. The retina is an attractive source of biomarkers since it shares many features with the brain. Some even describe the retina as a ‘window’ to the brain, implying that retinal signs are analogous to brain disease features. However, new analytical methods are needed to show whether or not retinal signs really are equivalent to brain abnormalities, since this requires greater evidence than direct associations between retina and brain. We, therefore propose a new way to think about, and test, how clearly one might see the brain through the retinal window, using cerebral malaria as a case study. PMID:26174843

  15. Management of retinal vascular diseases: a patient-centric approach

    PubMed Central

    Brand, C S

    2012-01-01

    Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases. PMID:22495396

  16. Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

    PubMed Central

    Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

    2016-01-01

    Background and purpose Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. Patients and methods We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. Results In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 105 person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 105 person-years in 1997 to 97 per 105 person-years in 2012, but not in Sweden. Interpretation The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries. PMID:26122621

  17. The Domestic Cat as a Large Animal Model for Characterization of Disease and Therapeutic Intervention in Hereditary Retinal Blindness

    PubMed Central

    Narfström, Kristina; Holland Deckman, Koren; Menotti-Raymond, Marilyn

    2011-01-01

    Large mammals, including canids and felids, are affected by spontaneously occurring hereditary retinal diseases with similarities to those of humans. The large mammal models may be used for thorough clinical characterization of disease processes, understanding the effects of specific mutations, elucidation of disease mechanisms, and for development of therapeutic intervention. Two well-characterized feline models are addressed in this paper. The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene. The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene. Therapeutic trials have been performed mainly in the former type including stem cell therapy, retinal transplantation, and development of ocular prosthetics. Domestic cats, having large human-like eyes with comparable spontaneous retinal diseases, are also considered useful for gene replacement therapy, thus functioning as effective model systems for further research. PMID:21584261

  18. Chronic sole ulcerations associated with degenerative bone disease in two Asian elephants (Elephas maximus).

    PubMed

    Luikart, Kimberly A; Stover, Susan M

    2005-12-01

    Chronic foot lesions and degenerative joint disease are common causes of morbidity in elephants. Lesions may become intractable and progressive despite intensive treatment regimens. The forelimbs of two Asian elephants (Elephas maximus) with chronic nonhealing sole ulcerations were examined using manual dissection and computed tomography. Both elephants had abnormal limb conformation that preceded the development of sole ulcerations. In both cases, sole ulcers were associated with remodeling and degeneration of underlying bones of the digits. Conformational abnormalities and altered weight distribution in these individuals may have induced compensatory bony degeneration and secondary ulcer formation. Sole ulcerations associated with digital abnormalities may have a guarded prognosis for resolution, even with aggressive treatment. Because limb conformational abnormalities could predispose to or result from chronic digital lesions, elephants with conformational abnormalities may have increased likelihood of having chronic sole ulcerations. PMID:17312727

  19. Symptoms and signs of degenerative back disease in concrete reinforcement workers.

    PubMed

    Wickström, G

    1978-01-01

    Concrete reinforcement work causes great static loads on the back from the prolonged adoption of bent-double work postures during the tying of steel rods and from substantial dynamic loads during the lifting and pulling of rods from the stack. Subjective manifestations and objective signs of "degenerative back disease" are common in active reinforcement workers. An age- and sex-adjusted comparison of the findings was, however, possible only with one other occupational group, computer technicians, who also often work in awkward positions. A history of sciatica and pain during forward bending in a clinical examination were significantly more common in reinforcement workers than in computer technicians. This finding suggests an effect of reinforcement work on the back, but definite conclusions require further study. PMID:149368

  20. Chemical pathology of homocysteine. V. Thioretinamide, thioretinaco, and cystathionine synthase function in degenerative diseases.

    PubMed

    McCully, Kilmer S

    2011-01-01

    Hyperhomocysteinemia was first associated with degenerative disease by observation of accelerated arteriosclerosis in children with inherited disorders of cystathionine synthase, methionine synthase, and methylene tetrohydrofolate reductase. The metabolic blockade of sulfate synthesis from homocysteine thiolactone in malignant cells is ascribed to a deficiency of a chemopreventive derivative of homocysteine thiolactone that occurs in normal cells. Its chemical structure was elucidated by the organic synthesis of thioretinamide from retinoic acid and homocysteine thiolactone. Oxidation of the sulfur atom of homocysteine is inhibited in scorbutic guinea pigs, demonstrating ascorbate function in sulfate synthesis from homocysteine. Studies of homocysteine metabolism in protein energy malnutrition led to the conclusion that the biosynthesis of thioretinamide from the retinol of transthyretin is catalyzed by dehydroascorbate and superoxide generated from the heme oxygenase group of cystathionine synthase. Newly synthesized thioretinamide is complexed with cobalamin to form thioretinaco, which is activated by ozone and oxygen to function as the active site of oxidative phosphorylation. In accordance with the trophoblastic theory of cancer, pancreatic enzymes are believed to be oncolytic because they hydrolyze the homocysteinylated proteins, nucleic acids and glycosaminoglycans of malignant tissues. The clonal selection of malignant cells that are deficient in the heme oxygenase function of cystathionine synthase produces cells dependent upon glycolysis for ATP synthesis, since they are deficient in synthesis of thioretinamide, thioretinaco and thioretinaco ozonide. The vulnerable plaque of arteriosclerosis originates from complexes of microbes with homocysteinylated lipoproteins, obstructing vasa vasorum narrowed by endothelial dysfunction, causing arterial ischemia, and intimal micro-abscesses. Degenerative diseases may be ameliorated by a proposed therapeutic protocol

  1. The Impact of Obesity on Perioperative Resource Utilization after Elective Spine Surgery for Degenerative Disease

    PubMed Central

    Planchard, Ryan F.; Higgins, Dominique M.; Mallory, Grant W.; Puffer, Ross C.; Jacob, Jeffrey T.; Curry, Timothy B.; Kor, Daryl J.; Clarke, Michelle J.

    2015-01-01

    Study Design Retrospective case series. Objective To determine the effect of obesity on the resource utilization and cost in 3270 consecutive patients undergoing elective noninstrumented decompressive surgeries for degenerative spine disease at Mayo Clinic Rochester between 2005 and 2012. Methods Groups were assessed for baseline differences (age, gender, and American Society of Anesthesiologists [ASA] classification, procedure type, and number of operative levels). Outcome variables included the transfusion requirements during surgery, the total anesthesia and surgical times, intensive care unit (ICU) admissions, standardized costs, as well as the ICU and hospital length of stay (LOS). Regression analysis was used to evaluate for strength of association between obesity and outcome variables. Results Baseline differences between the groups (nonobese: n = 1,853; obese: n = 1,417) were found with respect to age, ASA class, gender, procedure type, and number of operative levels. After correcting for differences, we found significant associations between obesity and surgical (p < 0.0001) and anesthesia times (p < 0.0001) and hospital LOS (p < 0.0001). Additionally, ICU admission rates (p = 0.02) and requirement for postoperative ventilation (p = 0.048) were significantly higher in obese patients. Finally, mean difference in total cost ($1,632, p < 0.0001) was significantly higher for the obese cohort. Conclusion Obesity is associated with increased resource utilization and cost in patients undergoing a noninstrumented decompressive surgery for degenerative spine disease. PMID:26225277

  2. Association between nutritional status and Modic classification in degenerative disc disease.

    PubMed

    Seyithanoglu, Hakan; Aydin, Teoman; Taşpınar, Ozgur; Camli, Adil; Kiziltan, Huriye; Eris, Ali Hikmet; Hocaoglu, Ilknur Turk; Ozder, Aclan; Denizli, Ebru; Kepekci, Muge; Keskin, Yasar; Mutluer, Ahmet Serdar

    2016-04-01

    [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age <20 years or >65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients' dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed. PMID:27190462

  3. Laser technologies in treatment of degenerative-dystrophic bone diseases in children

    NASA Astrophysics Data System (ADS)

    Abushkin, Ivan A.; Privalov, Valery A.; Lappa, Alexander V.; Noskov, Nikolay V.; Neizvestnykh, Elena A.; Kotlyarov, Alexander N.; Shekunova, Yulia G.

    2014-03-01

    Two low invasive laser technologies for treatment of degenerative-dystrophic bone diseases in children are presented. The first is the transcutaneous laser osteoperforation developed by us and initially applied for treatment of different inflammatory and traumatic diseases (osteomyelitides, osteal and osteoarticular panaritiums, delayed unions, false joints, and others). Now the technology was applied to treatment of aseptic osteonecrosis of different localizations in 134 children aged from 1 to 16 years, including 56 cases with necrosis of femoral head (Legg-Calve-Perthes disease), 42 with necrosis of 2nd metatarsal bone head (Kohler II disease), and 36 with necrosis of tibial tuberosity (Osgood-Schlatter disease). The second technology is the laser intracystic thermotherapy for treatment of bone cysts. The method was applied to 108 children aged from 3 to 16 years with aneurismal and solitary cysts of different localizations. In both technologies a 970 nm diode laser was used. The suggested technologies increase the efficiency of treatment, reduce its duration, can be performed on outpatient basis, which resulted in great economical effect.

  4. Association between nutritional status and Modic classification in degenerative disc disease

    PubMed Central

    Seyithanoglu, Hakan; Aydin, Teoman; Taşpınar, Ozgur; Camli, Adil; Kiziltan, Huriye; Eris, Ali Hikmet; Hocaoglu, Ilknur Turk; Ozder, Aclan; Denizli, Ebru; Kepekci, Muge; Keskin, Yasar; Mutluer, Ahmet Serdar

    2016-01-01

    [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age <20 years or >65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients’ dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed. PMID:27190462

  5. Reprint of "Ethical issues with artificial nutrition of children with degenerative brain diseases".

    PubMed

    Kohlschütter, Alfried; Riga, Carolina; Crespo, Dolores; Torres, José Manuel; Penchaszadeh, Victor; Schulz, Angela

    2015-10-01

    This report highlights viewpoints of the authors and comments from the auditory at a workshop, held during the 14th international Congress on neuronal ceroid lipofuscinoses (NCL) in Córdoba, Argentina, on ethical aspects of artificial nutrition in children with degenerative brain diseases. The discussion centers on what constitutes the best interest of a patient whose personality was immature before the onset of the disease, who has become demented during its course and is unable to communicate his/her own positions and desires. There is wide consensus that in a child with advanced disease who cannot be fed naturally, decisions to withhold nutrition or to institute or stop artificial nutrition, should only be made by parents (or their representatives) who are adequately prepared on an intellectual and emotional level. We try to show that such decisions are highly individual but can be made in a rationally and emotionally acceptable way after a careful and prolonged dialogue between families and professionals. A checklist summarizes important considerations. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". PMID:26071856

  6. Ethical issues with artificial nutrition of children with degenerative brain diseases.

    PubMed

    Kohlschütter, Alfried; Riga, Carolina; Crespo, Dolores; Torres, José Manuel; Penchaszadeh, Victor; Schulz, Angela

    2015-07-01

    This report highlights viewpoints of the authors and comments from the auditory at a workshop, held during the 14th international Congress on neuronal ceroid lipofuscinoses (NCL) in Córdoba, Argentina, on ethical aspects of artificial nutrition in children with degenerative brain diseases. The discussion centers on what constitutes the best interest of a patient whose personality was immature before the onset of the disease, who has become demented during its course and is unable to communicate his/her own positions and desires. There is wide consensus that in a child with advanced disease who cannot be fed naturally, decisions to withhold nutrition or to institute or stop artificial nutrition, should only be made by parents (or their representatives) who are adequately prepared on an intellectual and emotional level. We try to show that such decisions are highly individual but can be made in a rationally and emotionally acceptable way after a careful and prolonged dialogue between families and professionals. A checklist summarizes important considerations. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". PMID:25795594

  7. Spontaneous degenerative polioencephalomyelopathy in feeder pigs--a new motor neuron disease?

    PubMed

    Wohlsein, Peter; Brügmann, Michael; Pfeiffer, Ina; Ammer, Hermann; Wolf, Petra; Baumgartner, Wolfgang; Peters, Martin

    2012-01-01

    A central nervous disorder occurred spontaneously in a herd of feeder pigs characterized by muscle fasciculations, convulsions, squealing, and acute death in numerous animals. Histopathology revealed a degenerative poliomyeloencephalopathy of brain stem and spinal cord consisting of neuronal hypertrophy, chromatolysis, neuronophagia, and satellitosis associated with Wallerian degeneration of ventral rootlets and neurogenic muscle atrophy of limb musculature. The sudden onset of clinical signs and the pattern of morphological findings were suggestive of intoxication. Though parathion was found in two animals, serum acetylcholine esterase activity and morphological findings were not compatible with an organophosphate poisoning. A hereditary disorder was excluded by genetic analysis. Summarized findings in the present cases are reminiscent of changes observed in ruminants suffering from patulin poisoning, a neuromycotoxicosis caused by Aspergillus clavatus. However, toxicological and microbiological investigations failed to identify the cause of this unusual and so far not described disease in pigs. Morphologically, lesion distribution and alterations of motor neurons resemble changes observed in equine motor neuron disease, spinal muscular atrophy of certain canine breeds, and amyotrophic lateral sclerosis (Lou Gehrig's disease) in man. Therefore, the term spontaneous porcine motor neuron disease (SPMND) is proposed for this new and unique entitiy. PMID:23227771

  8. Induced Pluripotent Stem Cells and Outer Retinal Disease

    PubMed Central

    Yang, Jin; Cai, Bingcui; Glencer, Patrick; Li, Zhiqing; Zhang, Xiaomin; Li, Xiaorong

    2016-01-01

    The retina, which is composed of multiple layers of differing cell types, has been considered the first choice for gene therapy, disease modeling, and stem cell-derived retinal cell transplant therapy. Because of its special characteristics, the retina, located in the posterior part of the eye, can be well observed directly after gene therapy or transplantation. The blood-retinal barrier is part of a specialized ocular microenvironment that is immune privileged. This protects transplanted cells and tissue. Having two eyes makes perfect natural control possible after a single eye receives gene or stem cell therapy. For this reason, research about exploring retinal diseases' underlying molecular mechanisms and potential therapeutic approach using stem cell technique has been developing rapidly. This review is to present an up-to-date summary of the iPSC's sources, variations, differentiation methods, and the wide-ranging application of iPSCs-RPCS or iPSCs-RPE on retinal disease modeling, diagnostics, and therapeutics. PMID:26880948

  9. Characterization of Intercostal Muscle Pathology in Canine Degenerative Myelopathy: A Disease Model for Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Bujnak, Alyssa C.; Katz, Martin L.

    2014-01-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions accompanied by atrophic changes in the descending spinal cord tracts , and some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure due to severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and an alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  10. Predictive diagnostics and personalized medicine for the prevention of chronic degenerative diseases

    PubMed Central

    2010-01-01

    Progressive increase of mean age and life expectancy in both industrialized and emerging societies parallels an increment of chronic degenerative diseases (CDD) such as cancer, cardiovascular, autoimmune or neurodegenerative diseases among the elderly. CDD are of complex diagnosis, difficult to treat and absorbing an increasing proportion in the health care budgets worldwide. However, recent development in modern medicine especially in genetics, proteomics, and informatics is leading to the discovery of biomarkers associated with different CDD that can be used as indicator of disease’s risk in healthy subjects. Therefore, predictive medicine is merging and medical doctors may for the first time anticipate the deleterious effect of CDD and use markers to identify persons with high risk of developing a given CDD before the clinical manifestation of the diseases. This innovative approach may offer substantial advantages, since the promise of personalized medicine is to preserve individual health in people with high risk by starting early treatment or prevention protocols. The pathway is now open, however the road to an effective personalized medicine is still long, several (diagnostic) predictive instruments for different CDD are under development, some ethical issues have to be solved. Operative proposals for the heath care systems are now needed to verify potential benefits of predictive medicine in the clinical practice. In fact, predictive diagnostics, personalized medicine and personalized therapy have the potential of changing classical approaches of modern medicine to CDD. PMID:21172060

  11. Characterization of intercostal muscle pathology in canine degenerative myelopathy: a disease model for amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Bujnak, Alyssa C; Katz, Martin L

    2013-12-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. PMID:24043596

  12. Prioritization of Retinal Disease Genes: An Integrative Approach

    PubMed Central

    Wagner, Alex H.; Taylor, Kyle R.; DeLuca, Adam P.; Casavant, Thomas L.; Mullins, Robert F.; Stone, Edwin M.; Scheetz, Todd E.; Braun, Terry A.

    2015-01-01

    The discovery of novel disease-associated variations in genes is often a daunting task in highly heterogeneous disease classes. We seek a generalizable algorithm that integrates multiple publicly available genomic data sources in a machine-learning model for the prioritization of candidates identified in patients with retinal disease. To approach this problem, we generate a set of feature vectors from publicly available microarray, RNA-seq, and ChIP-seq datasets of biological relevance to retinal disease, to observe patterns in gene expression specificity among tissues of the body and the eye, in addition to photoreceptor-specific signals by the CRX transcription factor. Using these features, we describe a novel algorithm, positive and unlabeled learning for prioritization (PULP). This article compares several popular supervised learning techniques as the regression function for PULP. The results demonstrate a highly significant enrichment for previously characterized disease genes using a logistic regression method. Finally, a comparison of PULP with the popular gene prioritization tool ENDEAVOUR shows superior prioritization of retinal disease genes from previous studies. PMID:23508994

  13. Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia.

    PubMed

    Schön, Christian; Asteriti, Sabrina; Koch, Susanne; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Herms, Jochen; Seeliger, Mathias W; Cangiano, Lorenzo; Biel, Martin; Michalakis, Stylianos

    2016-03-15

    Most inherited blinding diseases are characterized by compromised retinal function and progressive degeneration of photoreceptors. However, the factors that affect the life span of photoreceptors in such degenerative retinal diseases are rather poorly understood. Here, we explore the role of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in this context. HCN1 is known to adjust retinal function under mesopic conditions, and although it is expressed at high levels in rod and cone photoreceptor inner segments, no association with any retinal disorder has yet been found. We investigated the effects of an additional genetic deletion of HCN1 on the function and survival of photoreceptors in a mouse model of CNGB1-linked retinitis pigmentosa (RP). We found that the absence of HCN1 in Cngb1 knockout (KO) mice exacerbated photoreceptor degeneration. The deleterious effect was reduced by expression of HCN1 using a viral vector. Moreover, pharmacological inhibition of HCN1 also enhanced rod degeneration in Cngb1 KO mice. Patch-clamp recordings revealed that the membrane potentials of Cngb1 KO and Cngb1/Hcn1 double-KO rods were both significantly depolarized. We also found evidence for altered calcium homeostasis and increased activation of the protease calpain in Cngb1/Hcn1 double-KO mice. Finally, the deletion of HCN1 also exacerbated degeneration of cone photoreceptors in a mouse model of CNGA3-linked achromatopsia. Our results identify HCN1 as a major modifier of photoreceptor degeneration and suggest that pharmacological inhibition of HCN channels may enhance disease progression in RP and achromatopsia patients. PMID:26740549

  14. MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

    PubMed

    Gutierrez-Quintana, Rodrigo; Penderis, Jacques

    2012-01-01

    Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. PMID:22236021

  15. General pathophysiology in retinal degeneration.

    PubMed

    Wert, Katherine J; Lin, Jonathan H; Tsang, Stephen H

    2014-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  16. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  17. Photobiomodulation for the treatment of retinal diseases: a review

    PubMed Central

    Geneva, Ivayla I.

    2016-01-01

    Photobiomodulation (PBM), also known as low level laser therapy, has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and possibly others. This review evaluates the existing research pertaining to PBM applications in the retina, with a focus on the mechanisms of action and clinical outcomes. All available literature until April 2015 was reviewed using PubMed and the following keywords: “photobiomodulation AND retina”, “low level light therapy AND retina”, “low level laser therapy AND retina”, and “FR/NIR therapy AND retina”. In addition, the relevant references listed within the papers identified through PubMed were incorporated. The literature supports the conclusion that the low-cost and non-invasive nature of PBM, coupled with the first promising clinical reports and the numerous preclinical-studies in animal models, make PBM well-poised to become an important player in the treatment of a wide range of retinal disorders. Nevertheless, large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases, as well as to gain a deeper understanding of its mechanisms of action. PMID:26949625

  18. Short term outcome of posterior dynamic stabilization system in degenerative lumbar diseases

    PubMed Central

    Yang, Mingyuan; Li, Chao; Chen, Ziqiang; Bai, Yushu; Li, Ming

    2014-01-01

    Background: Decompression and fusion is considered as the ‘gold standard’ for the treatment of degenerative lumbar diseases, however, many disadvantages have been reported in several studies, recently like donor site pain, pseudoarthrosis, nonunion, screw loosening, instrumentation failure, infection, adjacent segment disease (ASDis) and degeneration. Dynamic neutralization system (Dynesys) avoids many of these disadvantages. This system is made up of pedicle screws, polyethylene terephthalate cords, and polycarbonate urethane spacers to stabilize the functional spinal unit and preserve the adjacent motion after surgeries. This was a retrospective cohort study to compare the effect of Dynesys for treating degenerative lumbar diseases with posterior lumbar interbody fusion (PLIF) based on short term followup. Materials and Methods: Seventy five consecutive patients of lumbar degenerative disease operated between October 2010 and November 2012 were studied with a minimum followup of 2 years. Patients were divided into two groups according to the different surgeries. 30 patients underwent decompression and implantation of Dynesys in two levels (n = 29) or three levels (n = 1) and 45 patients underwent PLIF in two levels (n = 39) or three levels (n = 6). Clinical and radiographic outcomes between two groups were reviewed. Results: Thirty patients (male:17, female:13) with a mean age of 55.96 ± 7.68 years were included in Dynesys group and the PLIF group included 45 patients (male:21, female:24) with a mean age of 54.69 ± 3.26 years. The average followup in Dynesys group and PLIF group was 2.22 ± 0.43 year (range 2-3.5 year) and 2.17 ± 0.76 year (range 2-3 year), respectively. Dynesys group showed a shorter operation time (141.06 ± 11.36 min vs. 176.98 ± 6.72 min, P < 0.001) and less intraoperative blood loss (386.76 ± 19.44 ml vs. 430.11 ± 24.72 ml, P < 0.001). For Dynesys group, visual analogue scale (VAS) for back and leg pain improved from 6.87 ± 0

  19. Hyperspectral imaging for the detection of retinal disease

    NASA Astrophysics Data System (ADS)

    Harvey, Andrew R.; Lawlor, Joanne; McNaught, Andrew I.; Williams, John W.; Fletcher-Holmes, David W.

    2002-11-01

    Hyperspectral imaging (HSI) shows great promise for the detection and classification of several diseases, particularly in the fields of "optical biopsy" as applied to oncology, and functional retinal imaging in ophthalmology. In this paper, we discuss the application of HSI to the detection of retinal diseases and technological solutions that address some of the fundamental difficulties of spectral imaging within the eye. HSI of the retina offers a route to non-invasively deduce biochemical and metabolic processes within the retina. For example it shows promise for the mapping of retinal blood perfusion using spectral signatures of oxygenated and deoxygenated hemoglobin. Compared with other techniques using just a few spectral measurements, it offers improved classification in the presence of spectral cross-contamination by pigments and other components within the retina. There are potential applications for this imaging technique in the investigation and treatment of the eye complications of diabetes, and other diseases involving disturbances to the retinal, or optic-nerve-head circulation. It is well known that high-performance HSI requires high signal-to-noise ratios (SNR) whereas the application of any imaging technique within the eye must cope with the twin limitations of the small numerical aperture provided by the entrance pupil to the eye and the limit on the radiant power at the retina. We advocate the use of spectrally-multiplexed spectral imaging techniques (the traditional filter wheel is a traditional example). These approaches enable a flexible approach to spectral imaging, with wider spectral range, higher SNRs and lower light intensity at the retina than could be achieved using a Fourier-transform (FT) approach. We report the use of spectral imaging to provide calibrated spectral albedo images of healthy and diseased retinas and the use of this data for screening purposes. These images clearly demonstrate the ability to distinguish between

  20. Hybrid Surgery of Multilevel Cervical Degenerative Disc Disease : Review of Literature and Clinical Results

    PubMed Central

    Lee, Sang-Bok; Kim, Jong-Youn; Yoo, Do-Sung; Lee, Tae-Gyu; Huh, Pil-Woo

    2012-01-01

    Objective In the present study, we evaluated the effect, safety and radiological outcomes of cervical hybrid surgery (cervical disc prosthesis replacement at one level, and interbody fusion at the other level) on the multilevel cervical degenerative disc disease (DDD). Methods Fifty-one patients (mean age 46.7 years) with symptomatic multilevel cervical spondylosis were treated using hybrid surgery (HS). Clinical [neck disability index (NDI) and Visual Analogue Scale (VAS) score] and radiologic outcomes [range of motion (ROM) for cervical spine, adjacent segment and arthroplasty level] were evaluated at routine postoperative intervals of 1, 6, 12, 24 months. Review of other similar studies that examined the HS in multilevel cervical DDD was performed. Results Out of 51 patients, 41 patients received 2 level hybrid surgery and 10 patients received 3 level hybrid surgery. The NDI and VAS score were significantly decreased during the follow up periods (p<0.05). The cervical ROM was recovered at 6 and 12 month postoperatively and the mean ROM of inferior adjacent segment was significantly larger than that of superior adjacent segments after surgery. The ROM of the arthoplasty level was preserved well during the follow up periods. No surgical and device related complications were observed. Conclusion Hybrid surgery is a safe and effective alternative to fusion for the management of multilevel cervical spondylosis. PMID:23323165

  1. Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation

    PubMed Central

    Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Okano, Hideyuki; Edge, Albert S.B.

    2011-01-01

    Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies. PMID:21576819

  2. Deimination restores inner retinal visual function in murine demyelinating disease

    PubMed Central

    Enriquez-Algeciras, Mabel; Ding, Di; Mastronardi, Fabrizio G.; Marc, Robert E.; Porciatti, Vittorio; Bhattacharya, Sanjoy K.

    2013-01-01

    Progressive loss of visual function frequently accompanies demyelinating diseases such as multiple sclerosis (MS) and is hypothesized to be the result of damage to the axons and soma of neurons. Here, we show that dendritic impairment is also involved in these diseases. Deimination, a posttranslational modification, was reduced in the retinal ganglion cell layer of MS patients and in a transgenic mouse model of MS (ND4 mice). Reduced deimination accompanied a decrease in inner retinal function in ND4 mice, indicating loss of vision. Local restoration of deimination dramatically improved retinal function and elongation of neurites in isolated neurons. Further, neurite length was decreased by downregulation of deimination or siRNA knockdown of the export-binding protein REF, a primary target for deimination in these cells. REF localized to dendrites and bound selective mRNAs and translation machinery to promote protein synthesis. Thus, protein deimination and dendritic outgrowth play key roles in visual function and may be a general feature of demyelinating diseases. PMID:23281397

  3. AMD--the retinal disease with an unprecised etiopathogenesis: in search of effective therapeutics.

    PubMed

    Nowak, Jerzy Z

    2014-01-01

    AMD (age-related macular degeneration) is a progressive vision-threatening ocular disease, affecting central region of the retina--the macula--and manifesting in the elderly. AMD is a degenerative disease, and the degeneration affects primarily the retinal pigment epithelial (RPE) cells and secondarily the photoreceptors, leading consequently to disturbances or partial loss of central vision and legal blindness. Clinically, the disease is classified as: atrophic--dry AMD (in majority of cases), and neovascular--wet AMD (with choroidal neovascularization--CNV: 10-15% of all AMD cases). Pathogenesis of AMD is complex, multifactorial and only poorly recognized. Main risk factors include: advanced age, genetic predispositions, environmental determinants, history of exposure to intensive light and smoking. At least four molecular processes contribute to the development of AMD pathology: lipofuscinogenesis, drusogenesis, inflammation and choroidal neovascularization (in wet AMD). Since vascular endothelial growth factor (VEGF) is a predominant proangiogenic factor in CNV. the wet AMD can be treated with intravitreous application of "anti-VEGF" agents (Avastin, Lucentis, Eylea). Till now, there is no approved therapy for dry AMD, although several agents/treatments are currently in clinical trials. This paper briefly describes major molecular and cellular events leading to AMD, and presents currently used and new experimental therapeutic strategies against AMD. PMID:25745762

  4. Portable, low-priced retinal imager for eye disease screening

    NASA Astrophysics Data System (ADS)

    Soliz, Peter; Nemeth, Sheila; VanNess, Richard; Barriga, E. S.; Zamora, Gilberto

    2014-02-01

    The objective of this project was to develop and demonstrate a portable, low-priced, easy to use non-mydriatic retinal camera for eye disease screening in underserved urban and rural locations. Existing portable retinal imagers do not meet the requirements of a low-cost camera with sufficient technical capabilities (field of view, image quality, portability, battery power, and ease-of-use) to be distributed widely to low volume clinics, such as the offices of single primary care physicians serving rural communities or other economically stressed healthcare facilities. Our approach for Smart i-Rx is based primarily on a significant departure from current generations of desktop and hand-held commercial retinal cameras as well as those under development. Our techniques include: 1) Exclusive use of off-the-shelf components; 2) Integration of retinal imaging device into low-cost, high utility camera mount and chin rest; 3) Unique optical and illumination designed for small form factor; and 4) Exploitation of autofocus technology built into present digital SLR recreational cameras; and 5) Integration of a polarization technique to avoid the corneal reflex. In a prospective study, 41 out of 44 diabetics were imaged successfully. No imaging was attempted on three of the subjects due to noticeably small pupils (less than 2mm). The images were of sufficient quality to detect abnormalities related to diabetic retinopathy, such as microaneurysms and exudates. These images were compared with ones taken non-mydriatically with a Canon CR-1 Mark II camera. No cases identified as having DR by expert retinal graders were missed in the Smart i-Rx images.

  5. Melanopsin retinal ganglion cell loss in Alzheimer disease

    PubMed Central

    Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

    2015-01-01

    Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

  6. Modifier Genes as Therapeutics: The Nuclear Hormone Receptor Rev Erb Alpha (Nr1d1) Rescues Nr2e3 Associated Retinal Disease

    PubMed Central

    Cruz, Nelly M.; Yuan, Yang; Leehy, Barrett D.; Baid, Rinku; Kompella, Uday; DeAngelis, Margaret M.; Escher, Pascal; Haider, Neena B.

    2014-01-01

    Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erbα) rescues Nr2e3-associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations. PMID:24498227

  7. Intravitreal Steroids for the Treatment of Retinal Diseases

    PubMed Central

    Veritti, Daniele; Boscia, Francesco

    2014-01-01

    Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

  8. Intravitreal steroids for the treatment of retinal diseases.

    PubMed

    Sarao, Valentina; Veritti, Daniele; Boscia, Francesco; Lanzetta, Paolo

    2014-01-01

    Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

  9. Controversies about Interspinous Process Devices in the Treatment of Degenerative Lumbar Spine Diseases: Past, Present, and Future

    PubMed Central

    Galarza, Marcelo

    2014-01-01

    A large number of interspinous process devices (IPD) have been recently introduced to the lumbar spine market as an alternative to conventional decompressive surgery in managing symptomatic lumbar spinal pathology, especially in the older population. Despite the fact that they are composed of a wide range of different materials including titanium, polyetheretherketone, and elastomeric compounds, the aim of these devices is to unload spine, restoring foraminal height, and stabilize the spine by distracting the spinous processes. Although the initial reports represented the IPD as a safe, effective, and minimally invasive surgical alternative for relief of neurological symptoms in patients with low back degenerative diseases, recent studies have demonstrated less impressive clinical results and higher rate of failure than initially reported. The purpose of this paper is to provide a comprehensive overview on interspinous implants, their mechanisms of action, safety, cost, and effectiveness in the treatment of lumbar stenosis and degenerative disc diseases. PMID:24822224

  10. Retinal angiogenesis in development and disease

    NASA Astrophysics Data System (ADS)

    Gariano, Ray F.; Gardner, Thomas W.

    2004-12-01

    The retina has long been regarded as `an approachable part of the brain' for investigating neurosensory processes. Cell biologists are now capitalizing on the accessibility of the retina to investigate important aspects of developmental angiogenesis, including how it relates to neuronal and glial development, morphogenesis, oxygen sensing and progenitor cells. Pathological angiogenesis also occurs in the retina and is a major feature of leading blinding diseases, particularly diabetic retinopathy. The retina and its clinical disorders have a pivotal role in angiogenesis research and provide model systems in which to investigate neurovascular relationships and angiogenic diseases.

  11. Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats

    PubMed Central

    Gruen, Margaret E.; Griffith, Emily H.; Thomson, Andrea E.; Simpson, Wendy; Lascelles, B. Duncan X.

    2015-01-01

    Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease. PMID:26162101

  12. Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in dogs.

    PubMed

    Smith, G K; Popovitch, C A; Gregor, T P; Shofer, F S

    1995-03-01

    Passive coxofemoral joint laxity of dogs, as quantitated by a distraction-stress radiographic method, may have important prognostic value in determining susceptibility to hip dysplasia. Data from 151 dogs, representing 13 breeds, were included in a logistic regression model to evaluate the contribution of factors such as age, breed, weight, sex, distraction index, and Norberg angle to the risk of developing degenerative joint disease (DJD) of the coxofemoral joint. Of the factors studied, the amount of passive hip laxity, as quantitated by the distraction index, was the most significant (P < 0.0001) determinant of the risk to develop DJD of the coxofemoral joint. In the longitudinal and cross-sectional components of the study, distraction index was a significant (P < 0.001) risk factor for DJD, irrespective of age at evaluation (4, 12, or 24 months). The strength of the hip laxity:DJD correlation increased with the age of dog. In contrast, the Norberg angle, a measure of hip laxity on the standard hip-extended radiograph, was not found to be a significant risk factor for DJD, either in the longitudinal or cross-sectional analyses. Breed-specific probability curves of DJD susceptibility indicated that German Shepherd Dogs had a significantly (P < 0.05) greater risk of developing DJD than did the pool of non-German Shepherd Dogs. The information derived from this statistical model will help to scientifically characterize the role of passive hip laxity as a component in the pathogenesis of DJD of the coxofemoral joint. PMID:7744684

  13. Relationship of orthopedic examination, goniometric measurements, and radiographic signs of degenerative joint disease in cats

    PubMed Central

    2012-01-01

    Background Available information suggests a mismatch between radiographic and orthopedic examination findings in cats with DJD. However, the extent of the discrepancy between clinical and radiographic signs of OA in companion animals has not been described in detail. This study aimed to evaluate the relationship between orthopedic examination findings, joint goniometry, and radiographic signs of DJD in 100 cats, in a prospective observational design. Cat temperament, pain response to palpation, joint crepitus, effusion and thickening were graded. Radiographs of appendicular joints and the axial skeleton were made under sedation. Joint motion was measured by use of a plastic goniometer before and after sedation. Associations between radiographic degenerative joint disease (DJD) and examination findings were assessed to determine sensitivity, specificity and likelihood estimations. Results Pain response to palpation was elicited in 0-67% of the joints with DJD, with a specificity ranging from 62-99%; crepitus was detected in 0-56% of the joints and its specificity varied between 87 and 99%; for effusion, values ranged between 6 and 38% (specificity, 82-100%), and thickening, 0-59% (specificity, 74-99%). Joints with DJD tended to have a decreased range of motion. The presence of pain increased the odds of having DJD in the elbow (right: 5.5; left: 4.5); the presence of pain in the lower back increased the odds of spinal DJD being present (2.97 for lumbar; 4.67 for lumbo-sacral). Conclusions Radiographic DJD cannot be diagnosed with certainty using palpation or goniometry. However, negative findings tend to predict radiographically normal joints. Palpation and goniometry may be used as a tool to help to screen cats, mostly to rule out DJD. PMID:22281125

  14. Does degenerative disease of the lumbar spine cause arachnoiditis? A magnetic resonance study and review of the literature.

    PubMed

    Jackson, A; Isherwood, I

    1994-09-01

    The magnetic resonance appearances in 165 patients with symptoms suggestive of degenerative lumbar spine disease were reviewed. The aim of the study was to evaluate the relationship between abnormalities of nerve root distribution and degenerative disease of the lumbar spine in the absence of other known risk factors for arachnoiditis. Central clumping of nerve roots was present in 16 patients (9.7%) and was associated with spinal stenosis at one of the affected levels in all (p < 0.001). Spinal stenosis was present in 44 patients giving an incidence of abnormal nerve root distribution of 36% in this group. Nerve root clumping occurred in association with pure spinal stenosis (10 cases), stenosis secondary to disc prolapse (four cases) and degenerative spondylolisthesis (two cases). Nerve root clumping was confined to one vertebral level in nine cases and extended over two to four levels in seven. In five of the latter spinal stenosis was present at multiple levels. The appearance of nerve root clumping described here may result entirely from mechanical apposition of nerve roots but is indistinguishable from the central pattern of nerve root adhesions which occurs in adhesive lumbar arachnoiditis. No abnormalities of nerve root distribution were seen in association with any indicator of degenerative disk disease in the absence of stenosis. We have been unable to demonstrate the previously reported relationship between lumbar disk degeneration and arachnoiditis and discuss this with a critical review of the literature. Abnormal central clumping of nerve roots as described in arachnoiditis may occur in association with spinal stenosis in the absence of other risk factors although the cause for this appearance remains unexplained. Arachnoiditis-like changes extending over more than one vertebral level are rare (7%) except in the presence of spinal stenosis at multiple levels (29%). Awareness of this appearance may avoid a possibly incorrect diagnosis of arachnoiditis

  15. BEST1-related autosomal dominant vitreoretinochoroidopathy: a degenerative disease with a range of developmental ocular anomalies

    PubMed Central

    Vincent, A; McAlister, C; VandenHoven, C; Héon, E

    2011-01-01

    Purpose To describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation. Methods A retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1gene. Results A heterozygous change, p.V86M (c.256G>A), was identified in the BEST1gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from ⩾20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n=2), microcornea with shallow anterior chamber (n=1), iris dysgenesis (n=2), cataracts (n=4), classical peripheral concentric band of retinal hyperpigmentation (n=5), and optic nerve dysplasia (n=1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years). Conclusion ADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC. PMID:21072067

  16. Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease

    PubMed Central

    Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

    2013-01-01

    Background/purpose Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. Methods A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Results Three patients, 53–60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Conclusions Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction. PMID:23385633

  17. How Does Lumbar Degenerative Disc Disease Affect the Disc Deformation at the Cephalic Levels In Vivo?

    PubMed Central

    Wang, Shaobai; Xia, Qun; Passias, Peter; Li, Weishi; Wood, Kirkham; Li, Guoan

    2013-01-01

    Study Design Case-control study. Objective . To evaluate the effect of lumbar degenerative disc disease (DDD) on the disc deformation at the adjacent level and at the level one above the adjacent level during end ranges of lumbar motion. Summary of Background Data It has been reported that in patients with DDD, the intervertebral discs adjacent to the diseased levels have a greater tendency to degenerate. Although altered biomechanics have been suggested to be the causative factors, few data have been reported on the deformation characteristics of the adjacent discs in patients with DDD. Methods Ten symptomatic patients with discogenic low back pain between L4 and S1 and with healthy discs at the cephalic segments were involved. Eight healthy subjects recruited in our previous studies were used as a reference comparison. The in vivo kinematics of L3–L4 (the cephalic adjacent level to the degenerated discs) and L2–L3 (the level one above the adjacent level) lumbar discs of both groups were obtained using a combined magnetic resonance imaging and dual fluoroscopic imaging technique at functional postures. Deformation characteristics, in terms of areas of minimal deformation (defined as less than 5%), deformations at the center of the discs, and maximum tensile and shear deformations, were compared between the two groups at the two disc levels. Results In the patients with DDD, there were significantly smaller areas of minimal disc deformation at L3–L4 and L2–L3 than the healthy subjects (18% compared with 45% of the total disc area, on average). Both L2–L3 and L3–L4 discs underwent larger tensile and shear deformations in all postures than the healthy subjects. The maximum tensile deformations were higher by up to 23% (of the local disc height in standing) and the maximum shear deformations were higher by approximately 25% to 40% (of the local disc height in standing) compared with those of the healthy subjects. Conclusion Both the discs of the adjacent

  18. [Retinal vascular diseases reflecting generalized vascular alterations. What can be mutually learnt?].

    PubMed

    Feltgen, N; Franko Zeitz, P

    2014-01-01

    Retinal vascular diseases are mostly caused by systemic vascular diseases. In some cases the systemic disease is already known but in other patients ocular anomalies often provide the first indications of a systemic disease. Treating patients with vascular fundus diseases requires close cooperation between ophthalmologists and specialists in other fields and deciding which routine and specialized diagnostic examinations are necessary in light of the potential risk factors involved requires interdisciplinary communication. This article aims to provide an overview of the most important vascular retinal diseases and which examinations are required to ensure an accurate diagnosis. The retinal vascular diseases with the highest frequency or clinical relevance are hypertensive retinopathy, diabetic retinopathy, retinal vein occlusion and retinal artery occlusion. PMID:24448809

  19. Mimicking Retinal Development and Disease With Human Pluripotent Stem Cells.

    PubMed

    Sinha, Divya; Phillips, Jenny; Joseph Phillips, M; Gamm, David M

    2016-04-01

    As applications of human pluripotent stem cells (hPSCs) continue to be refined and pursued, it is important to keep in mind that the strengths and weaknesses of this technology lie with its developmental origins. The remarkable capacity of differentiating hPSCs to recapitulate cell and tissue genesis has provided a model system to study stages of human development that were not previously amenable to investigation and experimentation. Furthermore, demonstration of developmentally appropriate, stepwise differentiation of hPSCs to specific cell types offers support for their authenticity and their suitability for use in disease modeling and cell replacement therapies. However, limitations to farming cells and tissues in an artificial culture environment, as well as the length of time required for most cells to mature, are some of the many issues to consider before using hPSCs to study or treat a particular disease. Given the overarching need to understand and modulate the dynamics of lineage-specific differentiation in stem cell cultures, this review will first examine the capacity of hPSCs to serve as models of retinal development. Thereafter, we will discuss efforts to model retinal disorders with hPSCs and present challenges that face investigators who aspire to use such systems to study disease pathophysiology and/or screen for therapeutics. We also refer readers to recent publications that provide additional insight and details on these rapidly evolving topics. PMID:27116663

  20. Litanium expandable pedicle screw for the treatment of degenerative and traumatic spinal diseases in osteoporotic patients: preliminary experience.

    PubMed

    Gazzeri, Roberto; Roperto, Raffaelino; Fiore, Claudio

    2012-12-01

    Osteoporosis is a major global health problem, with over 10 million people currently diagnosed with the disease. Although 80% of osteoporotic patients are women, a considerable number of men are also affected. Also, due to increasing life expectancy, the number of elderly patients with osteoporosis affected by degenerative and traumatic spinal diseases will increase further. Osteoporosis reduces bone quality through negative bone remodelling. Low bone quality can reduce the pull-out strength of pedicle screw, and negative bone remodelling can cause delayed bone fusion. However, pedicle screw instrumentation of the osteoporotic spine carries an increased risk of screw loosening, pull-out, and fixation failure. Our preliminary study aims to investigate the efficiency of expandable pedicle screws (OsseoScrew-Spinal Fixation System, Alphatec Spine Inc., Carlsbad, CA) in osteoporotic spinal patients. All osteoporotic patients with degenerative and traumatic spinal diseases admitted in our department underwent a pre-operative spinal x-Ray and MRI or CT. Pre-operative clinical assesment of patients was based on the visual analog scale (VAS) and Owestry Disability (ODI) questionnaire-a disease-specific outcome measure. Ten osteoporotic patients were treated with expandable pedicle screws (OsseoScrew). Post-operative clinical assessment of patients was based on the VAS and ODI questionnaire at 3 months and 1 year of follow-up. Post-operative radiologic follow-up was performed after 3 days (CT, x-ray); 3 months (x-ray); 6 months (spinal CT); and 1 year (spinal CT). Expandable pedicle screws improved pull-out strength as compared to standard pedicle screws in osteoporotic patients with degenerative and traumatic spinal diseases. PMID:23023577

  1. Outcome of posterior lumbar interbody fusion versus posterolateral fusion in lumbar degenerative disease.

    PubMed

    Wu, Yungang; Tang, Hao; Li, Zhonghai; Zhang, Qiulin; Shi, Zhicai

    2011-06-01

    Between March 2003 and September 2007, 170 consecutive patients with lumbar degenerative disease were studied retrospectively. Eighty patients underwent posterior lumbar interbody fusion (PLIF group) with pedicle screw (PS) fixation, and 82 patients underwent posterolateral fusion (PLF group) with PS fixation. Eight patients were lost to follow-up. The minimum follow-up period in each group was 2.0years. The mean follow-up period for the PLIF group was 3.6years, and for the PLF group, the mean follow-up was 3.4years: there was no significant difference between the two groups for length of follow-up. The Pain Index (PI) improved from 66 to 27 in the PLF group (p<0.001) and from 69 to 29 in the PLIF group (p<0.001), but there was no significant difference between the two groups (p>0.05). In the PLF group, the preoperative mean Oswestry Disability Index (ODI) score was 34.5, which reduced to 14.2 at the final follow-up. In the PLIF group, the mean preoperative ODI was 36.4, which reduced to 16.2 at the final follow-up. There was no significant statistical difference between the two groups for ODI (p>0.05). Eighty-eight percent (n=72) of patients in the PLF group and 91% (n=73) in the PLIF group had radiologically confirmed union, with no significant difference in fusion percentage between the two groups (p>0.05). Twenty-two of 162 patients (14%) underwent a second operation: 18 (22%) in the PLF group and four (5%) patients in the PLIF group (p<0.001). The clinical and functional outcomes in both groups were similar, and no significant difference was found in the parameters tested. Both surgical procedures were effective, but patients in the PLF group showed more complications related to hardware biomechanics than patients in the PLIF group (p<0.001). PMID:21507656

  2. Analysis of Retinal Peripapillary Segmentation in Early Alzheimer's Disease Patients

    PubMed Central

    Salobrar-Garcia, Elena; Hoyas, Irene; Leal, Mercedes; de Hoz, Rosa; Rojas, Blanca; Ramirez, Ana I.; Salazar, Juan J.; Yubero, Raquel; Gil, Pedro; Triviño, Alberto; Ramirez, José M.

    2015-01-01

    Decreased thickness of the retinal nerve fiber layer (RNFL) may reflect retinal neuronal-ganglion cell death. A decrease in the RNFL has been demonstrated in Alzheimer's disease (AD) in addition to aging by optical coherence tomography (OCT). Twenty-three mild-AD patients and 28 age-matched control subjects with mean Mini-Mental State Examination 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision, were considered for study. OCT peripapillary and macular segmentation thickness were examined in the right eye of each patient. Compared to controls, eyes of patients with mild-AD patients showed no statistical difference in peripapillary RNFL thickness (P > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, while in sectors 1, 5, 6, 7, and 10 there was thickening. Total macular volume and RNFL thickness of the fovea in all four inner quadrants and in the outer temporal quadrants proved to be significantly decreased (P < 0.01). Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild-AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage. PMID:26557684

  3. Comparative sequence analyses of rhodopsin and RPE65 reveal patterns of selective constraint across hereditary retinal disease mutations.

    PubMed

    Hauser, Frances E; Schott, Ryan K; Castiglione, Gianni M; Van Nynatten, Alexander; Kosyakov, Alexander; Tang, Portia L; Gow, Daniel A; Chang, Belinda S W

    2016-01-01

    Retinitis pigmentosa (RP) comprises several heritable diseases that involve photoreceptor, and ultimately retinal, degeneration. Currently, mutations in over 50 genes have known links to RP. Despite advances in clinical characterization, molecular characterization of RP remains challenging due to the heterogeneous nature of causal genes, mutations, and clinical phenotypes. In this study, we compiled large datasets of two important visual genes associated with RP: rhodopsin, which initiates the phototransduction cascade, and the retinoid isomerase RPE65, which regenerates the visual cycle. We used a comparative evolutionary approach to investigate the relationship between interspecific sequence variation and pathogenic mutations that lead to degenerative retinal disease. Using codon-based likelihood methods, we estimated evolutionary rates (d N/d S) across both genes in a phylogenetic context to investigate differences between pathogenic and nonpathogenic amino acid sites. In both genes, disease-associated sites showed significantly lower evolutionary rates compared to nondisease sites, and were more likely to occur in functionally critical areas of the proteins. The nature of the dataset (e.g., vertebrate or mammalian sequences), as well as selection of pathogenic sites, affected the differences observed between pathogenic and nonpathogenic sites. Our results illustrate that these methods can serve as an intermediate step in understanding protein structure and function in a clinical context, particularly in predicting the relative pathogenicity (i.e., functional impact) of point mutations and their downstream phenotypic effects. Extensions of this approach may also contribute to current methods for predicting the deleterious effects of candidate mutations and to the identification of protein regions under strong constraint where we expect pathogenic mutations to occur. PMID:26750628

  4. Delivery of neurotrophic factors and therapeutic proteins for retinal diseases.

    PubMed

    Thanos, Chris; Emerich, Dwaine

    2005-11-01

    Neurotrophic factors have the ability to protect and initiate growth of neurons. In the central nervous system, neurotrophic factors are neuroprotective in a wide range of disease states. Similarly, disease pathologies of the neurosensory retina respond favourably in animal models of retinitis pigmentosa, macular degeneration, glaucoma and others. With advances in drug delivery and cell therapy, an almost universal increase in efficacy is being realised. Now, repeated injections of neurotrophic factors are being replaced by controlled delivery of cell-mediated factor secretion, reducing the number of potential acute side effects. Tissue engineering strategies in conjunction with gene-modulated protein therapy or gene transfer are creating a unique treatment niche and are quickly gaining acclaim in the clinic. This review surveys the founding and current work on neurotrophic factors such as CNTF, BDNF, GDNF, LEDGF, PEDF and others. Ongoing clinical trials and successful preclinical studies are summarised as well. PMID:16255648

  5. Near-Infrared Photobiomodulation in Retinal Injury and Disease.

    PubMed

    Eells, Janis T; Gopalakrishnan, Sandeep; Valter, Krisztina

    2016-01-01

    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. PMID:26427443

  6. The Retinal Disease Screening Study: Prospective Comparison of Nonmydriatic Fundus Photography and Optical Coherence Tomography for Detection of Retinal Irregularities

    PubMed Central

    Ouyang, Yanling; Heussen, Florian M.; Keane, Pearse A.; Sadda, SriniVas R.; Walsh, Alexander C.

    2013-01-01

    Purpose. To compare the sensitivity of volume scanning with optical coherence tomography (OCT) to nonmydriatic color fundus photography (FP) for the detection of retinal irregularities in asymptomatic populations. Methods. Asymptomatic subjects without known ocular disease were recruited over a 6-month period. For each eye, two undilated 45° fundus images and four undilated volume OCT image sets covering the macula and optic nerve were obtained. Color images were evaluated for irregularities both inside and outside the area covered by OCT. OCT image sets were evaluated for internal limiting membrane irregularities, abnormal retinal thickness, hyper/hyporeflective features, and photoreceptor/retinal pigment epithelium (RPE) irregularities. Detection sensitivities were compared and false-negative cases were analyzed. Results. A total of 284 eyes (144 subjects) were included, with a mean age of 38.1 years (range 18–77). Among 253 eyes (135 subjects) with gradable images from both FP and OCTs, the detection sensitivities for OCT were higher (96.2% infield and 85.7% in full field) than for FP (19.9% infield and 43.8% in full field) for all irregularities evaluated in the study (including epiretinal irregularities, abnormal retinal thickness, intraretinal hyperreflective/hyporeflective features, and photoreceptor/RPE irregularities). Overall, the presence of definite irregularities on either fundus imaging or OCT by eye in this asymptomatic population was 42.6% (121/284), with 39.4% (112/284) of eyes having RPE irregularities such as drusen. Conclusions. For detection of a variety of retinal irregularities evaluated in the current study, volume OCT scanning was more sensitive than nonmydriatic retinal photography in our asymptomatic individuals. OCT detected clinically relevant disease features, such as subretinal fluid, that were missed by FP, and had a lower ungradable image rate. It is likely that OCT will be added to photography screening in the near future for

  7. Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases.

    PubMed

    Cuenca, Nicolás; Fernández-Sánchez, Laura; Campello, Laura; Maneu, Victoria; De la Villa, Pedro; Lax, Pedro; Pinilla, Isabel

    2014-11-01

    Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types of stress or aging, but they all frequently induce a set of cell signals that lead to well-established and similar morphological and functional changes, including controlled cell death and retinal remodeling. Interestingly, an inflammatory response, oxidative stress and activation of apoptotic pathways are common features in all these diseases. Furthermore, it is important to note the relevant role of glial cells, including astrocytes, Müller cells and microglia, because their response to injury is decisive for maintaining the health of the retina or its degeneration. Several therapeutic approaches have been developed to preserve retinal function or restore eyesight in pathological conditions. In this context, neuroprotective compounds, gene therapy, cell transplantation or artificial devices should be applied at the appropriate stage of retinal degeneration to obtain successful results. This review provides an overview of the common and distinctive features of retinal neurodegenerative diseases, including the molecular, anatomical and functional changes caused by the cellular response to damage, in order to establish appropriate treatments for these pathologies. PMID:25038518

  8. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature.

    PubMed

    van den Eerenbeemt, Karin D; Ostelo, Raymond W; van Royen, Barend J; Peul, Wilco C; van Tulder, Maurits W

    2010-08-01

    The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the "gold standard" of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK Interbody Fusion System on a composite outcome of "clinical success" (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of "clinical success" (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial, with a high

  9. Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature

    PubMed Central

    van den Eerenbeemt, Karin D.; van Royen, Barend J.; Peul, Wilco C.; van Tulder, Maurits W.

    2010-01-01

    The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the “gold standard” of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK® Interbody Fusion System on a composite outcome of “clinical success” (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of “clinical success” (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial

  10. Sagittal balance of the pelvis-spine complex and lumbar degenerative diseases. A comparative study about 85 cases

    PubMed Central

    Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre

    2007-01-01

    Retrospective analysis of the spino-pelvic alignment in a population of 85 patients with a lumbar degenerative disease. Several previous publications reported the analysis of spino-pelvic alignment in the normal and low back pain population. Data suggested that patients with lumbar diseases have variations of sagittal alignment such as less distal lordosis, more proximal lumbar lordosis and a more vertical sacrum. Nevertheless most of these variations have been reported without reference to the pelvis shape which is well-known to strongly influence spino-pelvic alignment. The objective of this study was to analyse spino-pelvic parameters, including pelvis shape, in a population of 85 patients with a lumbar degenerative disease and compare these patients with a control group of normal volunteers. We analysed three different lumbar degenerative diseases: disc herniation (DH), n = 25; degenerative disc disease (DDD), n = 32; degenerative spondylolisthesis (DSPL), n = 28. Spino-pelvic alignment was analysed pre-operatively on full spine radiographs. Spino-pelvic parameters were measured as following: pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, thoracic kyphosis, spino-sacral angle and positioning of C7 plumb line. For each group of patients the sagittal profile was compared with a control population of 154 asymptomatic adults that was the subject of a previous study. In order to understand variations of spino-pelvic parameters in the patients’ population a stratification (matching) according to the pelvic incidence was done between the control group and each group of patients. Concerning first the pelvis shape, patients with DH and those with DDD demonstrated to have a mean pelvic incidence equal to 49.8° and 51.6°, respectively, versus 52° for the control group (no significant difference). Only young patients, less than 45 years old, with a disc disease (DH or DDD) demonstrated to have a pelvic incidence significantly lower (48.3°) than

  11. Willingness to pay for genetic testing for inherited retinal disease

    PubMed Central

    Tubeuf, Sandy; Willis, Thomas A; Potrata, Barbara; Grant, Hilary; Allsop, Matthew J; Ahmed, Mushtaq; Hewison, Jenny; McKibbin, Martin

    2015-01-01

    This paper investigates the willingness of adults with inherited retinal disease to undergo and pay for diagnostic genetic testing in three hypothetical scenarios and to explore the factors that influence decision making. Fifty patients were presented with three scenarios whereby genetic testing provided increasing information: confirming the diagnosis and inheritance pattern alone, providing additional information on future visual function, and identifying in addition a new treatment which could stabilise their condition. Willingness to pay (WTP) was elicited using an iterative bidding game. Regression analysis was used to investigate the probability of agreeing to and paying for testing. Qualitative data were also reviewed to provide a comprehensive understanding of WTP and decision making. The majority of participants agreed to undergo genetic testing in each of the three scenarios. Scenario 2 was the least acceptable with 78% of participants agreeing to genetic testing. The probability of agreeing to genetic testing decreased with age. Between 72 and 96% of participants reported a WTP for genetic testing. Average WTP was £539, £1516, and £6895 for scenarios 1, 2, and 3 respectively. Older participants and participants with higher incomes were willing to pay more for testing. Qualitative data provided additional detail about the rationale behind participants' decisions. The study suggests that patients with inherited retinal disease were willing to undergo and to pay for diagnostic genetic testing, suggesting that they valued the information it may provide. However, several patients preferred not to receive prognostic information and were less willing to pay for genetic testing that yielded such detail. PMID:24916649

  12. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures

    PubMed Central

    Patton, Niall; Aslam, Tariq; MacGillivray, Thomas; Pattie, Alison; Deary, Ian J; Dhillon, Baljean

    2005-01-01

    The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non-invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two-dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature. PMID:15817102

  13. Artificial Discs for Lumbar and Cervical Degenerative Disc Disease –Update

    PubMed Central

    2006-01-01

    Executive Summary Objective To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD). Clinical Need Degenerative disc disease is the term used to describe the deterioration of 1 or more intervertebral discs of the spine. The prevalence of DDD is roughly described in proportion to age such that 40% of people aged 40 years have DDD, increasing to 80% among those aged 80 years or older. Low back pain is a common symptom of lumbar DDD; neck and arm pain are common symptoms of cervical DDD. Nonsurgical treatments can be used to relieve pain and minimize disability associated with DDD. However, it is estimated that about 10% to 20% of people with lumbar DDD and up to 30% with cervical DDD will be unresponsive to nonsurgical treatments. In these cases, surgical treatment is considered. Spinal fusion (arthrodesis) is the process of fusing or joining 2 bones and is considered the surgical gold standard for DDD. Artificial disc replacement is the replacement of the degenerated intervertebral disc with an artificial disc in people with DDD of the lumbar or cervical spine that has been unresponsive to nonsurgical treatments for at least 6 months. Unlike spinal fusion, ADR preserves movement of the spine, which is thought to reduce or prevent the development of adjacent segment degeneration. Additionally, a bone graft is not required for ADR, and this alleviates complications, including bone graft donor site pain and pseudoarthrosis. It is estimated that about 5% of patients who require surgery for DDD will be candidates for ADR. Review Strategy The Medical Advisory Secretariat conducted a computerized search of the literature published between 2003 and September 2005 to answer the following questions: What is the effectiveness of ADR in people with DDD of the lumbar or cervical regions of the spine compared with spinal fusion surgery? Does an artificial disc reduce the incidence of adjacent segment degeneration (ASD

  14. Mid-range outcomes in 64 consecutive cases of multilevel fusion for degenerative diseases of the lumbar spine

    PubMed Central

    Röllinghoff, Marc; Schlüter-Brust, Klaus; Groos, Daniel; Sobottke, Rolf; Michael, Joern William-Patrick; Eysel, Peer; Delank, Karl Stefan

    2010-01-01

    In the treatment of multilevel degenerative disorders of the lumbar spine, spondylodesis plays a controversial role. Most patients can be treated conservatively with success. Multilevel lumbar fusion with instrumentation is associated with severe complications like failed back surgery syndrome, implant failure, and adjacent segment disease (ASD). This retrospective study examines the records of 70 elderly patients with degenerative changes or instability of the lumbar spine treated between 2002 and 2007 with spondylodesis of more than two segments. Sixty-four patients were included; 5 patients had died and one patient was lost to follow-up. We evaluated complications, clinical/radiological outcomes, and success of fusion. Flexion-extension and standing X-rays in two planes, MRI, and/or CT scans were obtained pre-operatively. Patients were assessed clinically using the Oswestry disability index (ODI) and a Visual Analogue Scale (VAS). Surgery performed was dorsolateral fusion (46.9%) or dorsal fusion with anterior lumbar interbody fusion (ALIF; 53.1%). Additional decompression was carried out in 37.5% of patients. Mean follow-up was 29.4±5.4 months. Average patient age was 64.7±4.3 years. Clinical outcomes were not satisfactory for all patients. VAS scores improved from 8.6±1.3 to 5.6±3.0 pre- to post-operatively, without statistical significance. ODI was also not significantly improved (56.1±22.3 pre- and 45.1±26.4 post-operatively). Successful fusion, defined as adequate bone mass with trabeculation at the facets and transverse processes or in the intervertebral segments, did not correlate with good clinical outcomes. Thirty-five of 64 patients (54%) showed signs of pedicle screw loosening, especially of the screws at S1. However, only 7 of these 35 (20%) complained of corresponding back pain. Revision surgery was required in 24 of 64 patients (38%). Of these, indications were adjacent segment disease (16 cases), pedicle screw loosening (7 cases), and

  15. Pedicle-Screw-Based Dynamic Systems and Degenerative Lumbar Diseases: Biomechanical and Clinical Experiences of Dynamic Fusion with Isobar TTL

    PubMed Central

    Barrey, Cédric; Perrin, Gilles; Champain, Sabina

    2013-01-01

    Dynamic systems in the lumbar spine are believed to reduce main fusion drawbacks such as pseudarthrosis, bone rarefaction, and mechanical failure. Compared to fusion achieved with rigid constructs, biomechanical studies underlined some advantages of dynamic instrumentation including increased load sharing between the instrumentation and interbody bone graft and stresses reduction at bone-to-screw interface. These advantages may result in increased fusion rates, limitation of bone rarefaction, and reduction of mechanical complications with the ultimate objective to reduce reoperations rates. However published clinical evidence for dynamic systems remains limited. In addition to providing biomechanical evaluation of a pedicle-screw-based dynamic system, the present study offers a long-term (average 10.2 years) insight view of the clinical outcomes of 18 patients treated by fusion with dynamic systems for degenerative lumbar spine diseases. The findings outline significant and stable symptoms relief, absence of implant-related complications, no revision surgery, and few adjacent segment degenerative changes. In spite of sample limitations, this is the first long-term report of outcomes of dynamic fusion that opens an interesting perspective for clinical outcomes of dynamic systems that need to be explored at larger scale. PMID:25031874

  16. Echocardiographic assessment of mitral valve morphology and performance after triangular resection of the prolapsing posterior leaflet for degenerative myxomatous disease.

    PubMed

    Chiappini, Bruno; Gregorini, Renato; De Remigis, Franco; Petrella, Licia; Villani, Carmine; Di Pietrantonio, Fabrizio; Pavicevic, Srdan; Mazzola, Alessandro

    2009-08-01

    The gold standard for the surgical treatment of prolapse of the posterior leaflet of the mitral valve (MV) for degenerative myxomatous disease has been represented by the quadrangular resection of the leaflet, according to the Carpentier technique. Since 2006 we performed a triangular resection of the prolapsing leaflet in 20 patients with myxomatous mitral regurgitation (MR). Seventeen patients (85%) underwent the triangular resection of P2; one patient (5%) had a triple scallops triangular resection (P1, P2, P3) and two (10%) a double scallops (P2, P3) resection. In this study, we report the immediate and mid-term clinical and echocardiographic results of a cohort of 20 patients, who underwent this technique. Thirty-day mortality was 0. Acute renal failure occurred in three patients (15%) and they resolved with conservative management. One patient (5%) required re-exploration for bleeding. At the mean follow-up of 13.1+/-4.2 months survival was 95%; one patient died of lymphoma during the follow-up time. All the cases were in New York Heart Association (NYHA) class I. Nineteen survivors underwent transthoracic echocardiography (TTE) (5), or transesophageal echocardiography (TEE) (13), performed by two skilled cardiologists. All patients showed no or trivial MV regurgitation. We believe that triangular resection of posterior MV leaflet (PMVL) provides excellent mid-term results providing the surgeon with a reliable and reproducible surgical option for myxomatous degenerative MV regurgitation. PMID:19414490

  17. Retinal diseases in a reference center from a Western Amazon capital city

    PubMed Central

    Malerbi, Fernando Korn; Matsudo, Nilson Hideo; Carneiro, Adriano Biondi Monteiro; Lottenberg, Claudio Luiz

    2015-01-01

    ABSTRACT Objective To describe retinal diseases found in patients who were waiting for treatment at a tertiary care hospital in Rio Branco, Acre, Brazil. Methods Patients underwent slit lamp biomicroscopy, dilated fundus exam and ocular ultrasound. Patients were classified according to phakic status and retinal disease of the most severely affected eye. Results A total of 138 patients were examined. The mean age was 51.3 years. Diabetes was present in 35.3% and hypertension in 45.4% of these patients. Cataract was found in 23.2% of patients, in at least one eye. Retinal examination was possible in 129 patients. The main retinal diseases identified were rhegmatogenous retinal detachment (n=23; 17.8%) and diabetic retinopathy (n=32; 24.8%). Out of 40 patients evaluated due to diabetes, 13 (32.5%) had absent or mild forms of diabetic retinopathy and did not need further treatment, only observation. Conclusion Diabetic retinopathy was the main retinal disease in this population. It is an avoidable cause of blindness and can be remotely evaluated, in its initial stages, by telemedicine strategies. In remote Brazilian areas, telemedicine may be an important tool for retinal diseases diagnosis and follow-up. PMID:26761550

  18. iPS Cells for Modelling and Treatment of Retinal Diseases

    PubMed Central

    Chen, Fred K.; McLenachan, Samuel; Edel, Michael; Da Cruz, Lyndon; Coffey, Peter J.; Mackey, David A.

    2014-01-01

    For many decades, we have relied on immortalised retinal cell lines, histology of enucleated human eyes, animal models, clinical observation, genetic studies and human clinical trials to learn more about the pathogenesis of retinal diseases and explore treatment options. The recent availability of patient-specific induced pluripotent stem cells (iPSC) for deriving retinal lineages has added a powerful alternative tool for discovering new disease-causing mutations, studying genotype-phenotype relationships, performing therapeutics-toxicity screening and developing personalised cell therapy. This review article provides a clinical perspective on the current and potential benefits of iPSC for managing the most common blinding diseases of the eye: inherited retinal diseases and age-related macular degeneration. PMID:26237613

  19. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

    PubMed Central

    Becker, Silke; Jayaram, Hari; Limb, G. Astrid

    2012-01-01

    Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

  20. Hybrid Surgery Combined with Dynamic Stabilization System and Fusion for the Multilevel Degenerative Disease of the Lumbosacral Spine

    PubMed Central

    Lee, Soo Eon; Kim, Hyun Jib

    2015-01-01

    Background As motion-preserving technique has been developed, the concept of hybrid surgery involves simultaneous application of two different kinds of devices, dynamic stabilization system and fusion technique. In the present study, the application of hybrid surgery for lumbosacral degenerative disease involving two-segments and its long-term outcome were investigated. Methods Fifteen patients with hybrid surgery (Hybrid group) and 10 patients with two-segment fusion (Fusion group) were retrospectively compared. Results Preoperative grade for disc degeneration was not different between the two groups, and the most common operated segment had the most degenerated disc grade in both groups; L4-5 and L5-S1 in the Hybrid group, and L3-4 and L4-5 in Fusion group. Over 48 months of follow-up, lumbar lordosis and range of motion (ROM) at the T12-S1 global segment were preserved in the Hybrid group, and the segmental ROM at the dynamic stabilized segment maintained at final follow-up. The Fusion group had a significantly decreased global ROM and a decreased segmental ROM with larger angles compared to the Hybrid group. Defining a 2-mm decrease in posterior disc height (PDH) as radiologic adjacent segment pathology (ASP), these changes were observed in 6 and 7 patients in the Hybrid and Fusion group, respectively. However, the last PDH at the above adjacent segment had statistically higher value in Hybrid group. Pain score for back and legs was much reduced in both groups. Functional outcome measured by Oswestry disability index (ODI), however, had better improvement in Hybrid group. Conclusion Hybrid surgery, combined dynamic stabilization system and fusion, can be effective surgical treatment for multilevel degenerative lumbosacral spinal disease, maintaining lumbar motion and delaying disc degeneration. PMID:26484008

  1. HLA analysis in patients with degenerative diseases of the temporomandibular joint.

    PubMed

    Learreta, Jorge A; Bono, Andrea E; Durst, Andreas C

    2011-01-01

    The aim of this study was to determine the presence of HLA alleles, specifically HLA-DR alleles, and to correlate them with clinical and radiological features of patients with degenerative processes (DP) of the temporomandibular joint (TMJ). The final goal was to determine which allele can be used to identify patients having more aggressive forms of the articular pathologies. Thirty-two (32) Caucasian patients with DP of the TMJ were included in the study. The SSOP (Luminex Corp., Austin, TX) method was used to determine class II HLA alleles. The presence of HLA-II DR in patients with DP of the TMJ was 98%. The presence of HLA was significantly higher in patients with DP of the TMJ than in healthy subjects (66%) (p=0.003). HLA DR52 was significantly more frequent in patients than in healthy individuals (40.62% vs. 13.79%, p = 0.041). While the percentage of DR11 positive individuals was also higher among patients than among healthy control subjects, the association with DP of the TMJ was not significant (p=0.220). Patients having the DR52 allele had higher deformation or DP. It was concluded that HLA-DR54 and DR11 alleles are associated with a higher susceptibility to DP of the TMJ, and HLA-DR54 and DR52 are associated with a higher severity of DP. PMID:21370767

  2. Functional imaging of inherited retinal disease with a commercial optical coherence tomography device

    NASA Astrophysics Data System (ADS)

    Theelen, T.; Hoyng, C. B.; Klevering, B. J.; Cense, B.

    2011-06-01

    Retinal dystrophies (RD) are blinding diseases affecting visual acuity mostly at young age. Intrinsic optical signals (IOS) on optical coherence tomography (OCT) may give topographical information on injure of retinal function in these patients. We demonstrate light response of the healthy and diseased human retina by IOS on a commercially available spectral-domain OCT. Significant IOS could be measured in the healthy retina and in unchanged retinal sectors of the RD patients. Main responses were located in the outer retina (photoreceptors) and the nerve fiber layer. In affected areas of RD eyes IOS were significantly reduced or even absent. Functional OCT imaging was able to give information about retinal function in RD patients on a micrometer scale. These results could be of value for refined disease analysis and control of upcoming gene therapy studies.

  3. Relationship between retinal vascular occlusions and incident cerebrovascular diseases: A systematic review and meta-analysis.

    PubMed

    Zhou, Yue; Zhu, Wengen; Wang, Changyun

    2016-06-01

    Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD.We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software.A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21-3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24-1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12-3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03-1.48; P = 0.04) were significantly associated with increased risk of CVD.Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  4. Investigation of SLA4A3 as a candidate gene for human retinal disease.

    PubMed

    Downs, Louise M; Webster, Andrew R; Moore, Anthony T; Michaelides, Michel; Ali, Robin R; Hardcastle, Alison J; Mellersh, Cathryn S

    2016-01-01

    SLC4A3 has been shown to cause retinal degeneration in a genetically engineered knockout mouse, and in a naturally occurring form of canine progressive retinal atrophy considered to be the equivalent of retinitis pigmentosa in humans (RP). This study was undertaken to investigate if SLC4A3 coding variants were implicated in human retinal degeneration. SLC4A3 exons were amplified and sequenced in 200 patients with autosomal recessive retinal degeneration who had no known molecular diagnosis for their condition, which included 197 unrelated individuals with suspected RP and three individuals with other forms of retinal disease. Three rare variants were identified that were predicted to be potentially pathogenic, however each variant was heterozygous in a single patient and therefore not considered disease-causing in isolation. Of these three variants, SNP-3 was the rarest, with an allele frequency of 7.06 x 10(-5) (>46,000 exomes from the ExAC database). In conclusion, no compound heterozygous or homozygous potentially pathogenic variants were identified that would account for recessive RP or retinal degeneration in this cohort, however the possibility remains that the rare variants identified could be acting with as yet undiscovered mutations in introns or regulatory regions. SLC4A3 remains an excellent candidate gene for human retinal degeneration, and with the advent of whole exome and whole genome sequencing of cohorts of molecularly unsolved patients with syndromic and non-syndromic forms of retinal degeneration, SLC4A3 may yet be implicated in human disease. PMID:27211793

  5. Polarimetric imaging of retinal disease by polarization sensitive SLO

    NASA Astrophysics Data System (ADS)

    Miura, Masahiro; Elsner, Ann E.; Iwasaki, Takuya; Goto, Hiroshi

    2015-03-01

    Polarimetry imaging is used to evaluate different features of the macular disease. Polarimetry images were recorded using a commercially- available polarization-sensitive scanning laser opthalmoscope at 780 nm (PS-SLO, GDx-N). From data sets of PS-SLO, we computed average reflectance image, depolarized light images, and ratio-depolarized light images. The average reflectance image is the grand mean of all input polarization states. The depolarized light image is the minimum of crossed channel. The ratio-depolarized light image is a ratio between the average reflectance image and depolarized light image, and was used to compensate for variation of brightness. Each polarimetry image is compared with the autofluorescence image at 800 nm (NIR-AF) and autofluorescence image at 500 nm (SW-AF). We evaluated four eyes with geographic atrophy in age related macular degeneration, one eye with retinal pigment epithelium hyperplasia, and two eyes with chronic central serous chorioretinopathy. Polarization analysis could selectively emphasize different features of the retina. Findings in ratio depolarized light image had similarities and differences with NIR-AF images. Area of hyper-AF in NIR-AF images showed high intensity areas in the ratio depolarized light image, representing melanin accumulation. Areas of hypo-AF in NIR-AF images showed low intensity areas in the ratio depolarized light images, representing melanin loss. Drusen were high-intensity areas in the ratio depolarized light image, but NIR-AF images was insensitive to the presence of drusen. Unlike NIR-AF images, SW-AF images showed completely different features from the ratio depolarized images. Polarization sensitive imaging is an effective tool as a non-invasive assessment of macular disease.

  6. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach

    PubMed Central

    Platania, Chiara B. M.; Di Paola, Luisa; Leggio, Gian M.; Romano, Giovanni L.; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

    2015-01-01

    Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in silico analysis of interaction of vascular endothelial growth factor A (VEGFA), the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD) coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW) energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon) of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff) of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice. PMID:26578958

  7. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach.

    PubMed

    Platania, Chiara B M; Di Paola, Luisa; Leggio, Gian M; Romano, Giovanni L; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

    2015-01-01

    Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in silico analysis of interaction of vascular endothelial growth factor A (VEGFA), the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD) coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW) energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon) of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff) of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice. PMID:26578958

  8. Adjunctive use of systematic retinal thickness map analysis to monitor disease activity in punctate inner choroidopathy.

    PubMed

    Madhusudhan, Savitha; Keane, Pearse A; Denniston, Alastair K

    2016-12-01

    A challenge in the management of 'white dot syndromes' is the lack of sensitive objective measures of disease activity. Retinal thickness maps from spectral domain optical coherence tomography (SD-OCT) inform treatment decisions in other retinal conditions such as age-related macular degeneration and diabetic maculopathy. In this report, we demonstrate their value in providing quantitative monitoring of a patient with punctate inner choroidopathy (PIC). Retinal thickness maps referenced against a baseline scan reliably detected focal areas of increased macular volume in active PIC lesions during symptomatic episodes, highlighting these as 'hot spots' that could be quantified, providing an objective basis for treatment decisions. PMID:26965893

  9. Tissue engineering the retinal ganglion cell nerve fiber layer.

    PubMed

    Kador, Karl E; Montero, Ramon B; Venugopalan, Praseeda; Hertz, Jonathan; Zindell, Allison N; Valenzuela, Daniel A; Uddin, Mohammed S; Lavik, Erin B; Muller, Kenneth J; Andreopoulos, Fotios M; Goldberg, Jeffrey L

    2013-06-01

    Retinal degenerative diseases, such as glaucoma and macular degeneration, affect millions of people worldwide and ultimately lead to retinal cell death and blindness. Cell transplantation therapies for photoreceptors demonstrate integration and restoration of function, but transplantation into the ganglion cell layer is more complex, requiring guidance of axons from transplanted cells to the optic nerve head in order to reach targets in the brain. Here we create a biodegradable electrospun (ES) scaffold designed to direct the growth of retinal ganglion cell (RGC) axons radially, mimicking axon orientation in the retina. Using this scaffold we observed an increase in RGC survival and no significant change in their electrophysiological properties. When analyzed for alignment, 81% of RGCs were observed to project axons radially along the scaffold fibers, with no difference in alignment compared to the nerve fiber layer of retinal explants. When transplanted onto retinal explants, RGCs on ES scaffolds followed the radial pattern of the host retinal nerve fibers, whereas RGCs transplanted directly grew axons in a random pattern. Thus, the use of this scaffold as a cell delivery device represents a significant step towards the use of cell transplant therapies for the treatment of glaucoma and other retinal degenerative diseases. PMID:23489919

  10. Tissue Engineering the Retinal Ganglion Cell Nerve Fiber Layer

    PubMed Central

    Kador, Karl E.; Montero, Ramon B.; Venugopalan, Praseeda; Hertz, Jonathan; Zindell, Allison N.; Valenzuela, Daniel A.; Uddin, Mohammed S.; Lavik, Erin B.; Muller, Kenneth J.; Andreopoulos, Fotios M.; Goldberg, Jeffrey L.

    2013-01-01

    Retinal degenerative diseases, such as glaucoma and macular degeneration, affect millions of people worldwide and ultimately lead to retinal cell death and blindness. Cell transplantation therapies for photoreceptors demonstrate integration and restoration of function, but transplantation into the ganglion cell layer is more complex, requiring guidance of axons from transplanted cells to the optic nerve head in order to reach targets in the brain. Here we create a biodegradable electrospun (ES) scaffold designed to direct the growth of retinal ganglion cell (RGC) axons radially, mimicking axon orientation in the retina. Using this scaffold we observed an increase in RGC survival and no significant change in their electrophysiological properties. When analyzed for alignment, 81% of RGCs were observed to project axons radially along the scaffold fibers, with no difference in alignment compared to the nerve fiber layer of retinal explants. When transplanted onto retinal explants, RGCs on ES scaffolds followed the radial pattern of the host retinal nerve fibers, whereas RGCs transplanted directly grew axons in a random pattern. Thus, the use of this scaffold as a cell delivery device represents a significant step towards the use of cell transplant therapies for the treatment of glaucoma and other retinal degenerative diseases. PMID:23489919

  11. The Unfolded Protein Response in Retinal Vascular Diseases: Implications and Therapeutic Potential Beyond Protein Folding

    PubMed Central

    Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.; Wang, Joshua J.

    2015-01-01

    Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness. PMID:25529848

  12. The degenerative cervical spine.

    PubMed

    Llopis, E; Belloch, E; León, J P; Higueras, V; Piquer, J

    2016-04-01

    Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. PMID:26878769

  13. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration.

    PubMed

    Koenekoop, Robert K; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I; Cheng, Jingliang; Logan, Clare V; McKibbin, Martin; Hayward, Bruce E; Parry, David A; Johnson, Colin A; Nageeb, Mohammed; Poulter, James A; Mohamed, Moin D; Jafri, Hussain; Rashid, Yasmin; Taylor, Graham R; Keser, Vafa; Mardon, Graeme; Xu, Huidan; Inglehearn, Chris F; Fu, Qing; Toomes, Carmel; Chen, Rui

    2012-09-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. PMID:22842230

  14. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

    PubMed Central

    Koenekoop, Robert K.; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A.; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I.; Cheng, Jingliang; Logan, Clare V.; McKibbin, Martin; Hayward, Bruce E.; Parry, David A.; Johnson, Colin A.; Nageeb, Mohammed; Poulter, James A.; Mohamed, Moin D.; Jafri, Hussain; Rashid, Yasmin; Taylor, Graham R.; Keser, Vafa; Mardon, Graeme; Xu, Huidan; Inglehearn, Chris F.; Fu, Qing; Toomes, Carmel; Chen, Rui

    2013-01-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wlds) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. PMID:22842230

  15. The Role of X-Chromosome Inactivation in Retinal Development and Disease

    PubMed Central

    Fahim, Abigail T.; Daiger, Stephen P.

    2016-01-01

    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. PMID:26427428

  16. DIETARY HYPERGLYCEMIA, GLYCEMIC INDEX AND METABOLIC RETINAL DISEASES

    PubMed Central

    Chiu, Chung-Jung; Taylor, Allen

    2014-01-01

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0~2 h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4~6 h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that

  17. Idiopathic REM sleep behavior disorder in the transition to degenerative disease.

    PubMed

    Postuma, Ronald B; Gagnon, Jean-Francois; Vendette, Melanie; Montplaisir, Jacques Y

    2009-11-15

    Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with "Alzheimer's disease" seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new-onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary "RBD-then-neurodegeneration" process, the clinical presentation of which depends upon selective neuronal vulnerability. PMID:19768814

  18. Retinal microvascular caliber and chronic kidney disease in an Asian population.

    PubMed

    Sabanayagam, Charumathi; Shankar, Anoop; Koh, David; Chia, Kee Seng; Saw, Seang Mei; Lim, Su Chi; Tai, E Shyong; Wong, Tien Yin

    2009-03-01

    Retinal arteriolar narrowing is a marker of microvascular damage from elevated blood pressure. Between August 2004 and June 2006, the authors examined the association between retinal vascular diameter and chronic kidney disease in a population-based cohort of 3,280 community-dwelling adults of Malay ethnicity aged 40-80 years living in Singapore. Chronic kidney disease was defined as 1) an estimated glomerular filtration rate (eGFR) of <60 mL/minute/1.73 m(2) from serum creatinine or 2) the presence of micro/macroalbuminuria defined as urinary albumin:creatinine ratios of > or = 17 mg/g for men and > or = 25 mg/g for women. Retinal arteriolar and venular diameters were measured and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Individuals with reduced CRAE were more likely to have chronic kidney disease than those with increased CRAE. After controlling for age, gender, education, smoking, diabetes, hypertension, body mass index, and total and high density lipoprotein cholesterol, the authors found the odds ratio comparing the smallest with the largest CRAE quartile to be 1.42 (95% confidence interval: 1.03, 1.96; P(trend) = 0.02) for eGFR of <60 mL/minute/1.73 m(2) and 1.80 (95% confidence interval: 1.11, 2.91; P(trend) = 0.01) for micro/macroalbuminuria. Retinopathy was also found to be positively associated with both eGFR and micro/macroalbuminuria. Retinal venular diameter was not associated with chronic kidney disease. These data suggest that retinal arteriolar narrowing is associated with chronic kidney disease, independent of diabetes and hypertension. PMID:19092170

  19. Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy.

    PubMed

    Borgarelli, Michele; Haggstrom, Jens

    2010-07-01

    Myxomatous mitral valve disease is a common condition in geriatric dogs. Most dogs affected are clinically asymptomatic for a long time. However, about 30% of these animals present a progression to heart failure and eventually die as a consequence of the disease. Left atrial enlargement, and particularly a change in left atrial size, seems to be the most reliable predictor of progression in some studies, however further studies are needed to clarify how to recognize asymptomatic patients at higher risk of developing heart failure. According to the published data on the natural history of the disease and the results of published studies evaluating the effect of early therapy on delaying the progression of the disease, it seems that no currently available treatment delays the onset of clinical signs of congestive heart failure (CHF). Although the ideal treatment of more severely affected dogs is probably surgical mitral valve repair or mitral valve replacement, this is not a currently available option. The results of several clinical trials together with clinical experience suggest that dogs with overt CHF can be managed with acceptable quality of life for a relatively long time period with medical treatment including furosemide, an angiotensin-converting enzyme inhibitor, pimobendan, and spironolactone. PMID:20610017

  20. Huntington disease: a single-gene degenerative disorder of the striatum

    PubMed Central

    Nopoulos, Peggy C.

    2016-01-01

    Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention. PMID:27069383

  1. Repackaging FDA-approved drugs for degenerative diseases: promises and challenges.

    PubMed

    Cummings, Jeffrey L; Zhong, Kate

    2014-03-01

    Repurposing refers to the therapeutic use of a drug or drug candidate for a disease other than that for which it was originally intended. Repurposing is attractive as a drug development strategy since much is known about approved agents including their drug-likeness and pharmacokinetic features, dosing, safety, tolerability, formulation and manufacturing. Time savings are also robust accounting for several years of the drug development cycle. Tissue and cell-based assays, epidemiologic information and human studies identify approved drugs that might be repurposed from use in Alzheimer's disease and other neurodegenerative disorders. The total number of compounds available for repurposing that are brain-penetrant is relatively small. Intellectual property and patent protection issues for repurposed drugs are hurdles for this approach to drug development. Repurposing may contribute importantly to development of new therapies for neurodegenerative disorders. PMID:24502586

  2. Hybrid surgery versus anterior cervical discectomy and fusion for multilevel cervical degenerative disc diseases: a meta-analysis.

    PubMed

    Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long

    2015-01-01

    The objective of this meta-analysis is to compare hybrid surgery (HS) and cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc diseases (DDD). Systematic searches of all published studies through March 2015 were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs involving HS and ACDF for multilevel DDD were included. All literature was searched and assessed by two independent reviewers according to the standard of Cochrane systematic review. Data of functional and radiological outcomes in two groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis revealed significant differences in blood loss (p = 0.005), postoperative C2-C7 ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group. No significant differences were found regarding operation time (p = 0.75), postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups. Hybrid surgery demonstrated excellent clinical efficacy and radiological results. Postoperative C2-C7 ROM was closer to the physiological status. No decrease in the ROM of the adjacent segment was noted in the hybrid surgery group. PMID:26307360

  3. Long-Term Follow-Up of the Cheilectomy for Degenerative Joint Disease of the First Metatarsophalangeal Joint.

    PubMed

    Nicolosi, Nicole; Hehemann, Chris; Connors, James; Boike, Allan

    2015-01-01

    Cheilectomy is the surgical resection of 20% to 30% of the dorsal metatarsal head and proximal phalanx. The present retrospective study evaluated the long-term efficacy of aggressive cheilectomy to address degenerative joint disease of the first metatarsophalangeal joint. To our knowledge, this is the second longest duration study to date to evaluate the long-term efficacy of the cheilectomy procedure, with a mean follow-up period of 7.14 years (range 39 weeks to 14.87 years). The mean patient age was 55.71 ± 9.51 years, and 37 (65%) of the patients were female. Age, sex, foot type, and preoperative radiographic parameters of hallux rigidus were also evaluated and correlated. The mean percentage of success with this operation was 87.69%. Of the 58 patients, 51 (87.93%) experienced no limitations in their daily activities. Only 2 patients (3.33%) subsequently required subsequent arthrodesis. The results of the present study suggest that cheilectomy offers long-term satisfaction for patients with hallux rigidus and is an acceptable alternative to the joint destructive procedure of first metatarsophalangeal arthrodesis. PMID:25981441

  4. Thoracolumbar spinal cord compression due to vertebral process degenerative joint disease in a family of Shiloh Shepherd dogs.

    PubMed

    McDonnell, John J; Knowles, Kim E; deLahunta, Alexander; Bell, Jerold S; Lowrie, Charles T; Todhunter, Rory J

    2003-01-01

    Five young Shiloh Shepherd Dogs (4 males and 1 female) related by a common sire were studied because of progressive pelvic limb weakness and incoordination. All dogs had a spastic paraparesis and pelvic limb ataxia consistent with an upper motor neuron and general proprioceptive lesion between spinal cord segments T3 and L3. Proliferative lesions involving one or more of the articular processes from the 11th thoracic vertebrae to the 2nd lumbar vertebra were observed on radiographs of the thoracolumbar vertebrae. Dorsal compression of the spinal cord was identified during imaging studies at these sites. Abnormalities of the synovial joints and bony proliferation of the involved articular processes were identified at postmortem examination in 2 dogs. The articular processes and associated vertebral arches protruded into the vertebral canal, indenting the dorsal surface of the spinalcord. Degenerative joint disease (DJD) was identified histologically. A compressive myelopathy was diagnosed in the spinal cord. These dogs were affected by a compressive myelopathy as a consequence of vertebral process DJD that likely has a geneticcomponent. The DJD could have been caused by a primary vertebral malformation or an injury to the processes at a young age causing malarticulation. PMID:12892304

  5. Evaluation of Retinal Vessel Morphology in Patients with Parkinson's Disease Using Optical Coherence Tomography

    PubMed Central

    Hidding, Ute; Keserü, Matthias; Keserü, Diana; Hassenstein, Andrea; Stemplewitz, Birthe

    2016-01-01

    Purpose The retina has been found affected in Parkinson’s disease (PD). It is unclear if this is due to neurodegeneration of local dopamine-dependent retinal cells, a result of central nervous degeneration including the optic nerve or retinal small vessel disease. This study aimed to detect changes of the retinal vasculature in PD patients compared to controls. Methods We examined 49 PD patients and 49 age- and sex-matched healthy controls by spectral domain optical coherence tomography (SD-OCT) with a circular scan centred at the optic disc. Vessels within the retinal nerve fibre layer were identified by an automated algorithm and thereafter manually labelled as artery or vein. Layer segmentation, vessel lumen and direct surrounding tissue were marked automatically with a grey value and the contrast between both values in relation to the surrounding tissue was calculated. The differences in these grey value ratios among subjects were determined and used as an indicator for differences in vessel morphology. Furthermore, the diameters of the veins and arteries were measured and then compared between the groups. Results The contrast of retinal veins was significantly lower in PD patients compared to controls, which indicates changes in vessel morphology in PD. The contrast of arteries was not significantly different. Disease duration, disease stage according to Hoehn and Yahr or age did not influence the grey value ratios in PD patients. Vessel diameter in either veins or arteries did not differ between subject groups. The contrast of retinal veins contralateral to the clinically predominant and first affected side was significantly lower compared to the ipsilateral side. Conclusion Our data show a potential difference of the retinal vasculature in PD patients compared to controls. Vascular changes in the retina of PD patients might contribute to vision-related complaints in PD. PMID:27525728

  6. Recent Clinical Applications of Laser Speckle Flowgraphy in Eyes with Retinal Disease.

    PubMed

    Kunikata, Hiroshi; Nakazawa, Toru

    2016-01-01

    Retinal diseases related to ischemia, such as diabetic retinopathy, are the main cause of blindness worldwide. However, the pathogenesis of these diseases remains unclear, as does the time course of associated changes in ocular blood flow. Laser speckle flowgraphy (LSFG), which uses the laser speckle phenomenon to detect and quantify ocular circulation, is a promising candidate for a noninvasive method to measure ocular blood flow in living eyes. A recently developed LSFG measurement parameter, mean blur rate (MBR), can serve as a quantitative and reproducible index of retinal blood cell velocity. Mean blur rate can be used in the study of retinal diseases to evaluate microcirculation in the retinal vessels, choroid, and optic nerve head. In addition to overall MBR (MA), LSFG measurements of optic nerve head microcirculation can be divided into vessel-area MBR (MV) and tissue-area MBR (MT). Absolute values for MT have been shown to be linearly correlated with capillary blood flow, regardless of fundus pigmentation. Recently, there has been an increasing number of reports on the clinical applications of LSFG in retinal disease. PMID:26649761

  7. Unusual presentation: pulmonary hemosiderosis with celiac disease and retinitis pigmentosa in a child.

    PubMed

    Keskin, Ozlem; Keskin, Mehmet; Guler, Elif; Tutar, Ediz; Saygili, Oguzhan; Kucukosmanoglu, Ercan; Kor, Yilmaz; Celik, Haydar; Coskun, Enes

    2011-08-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare disease characterized by anemia, hemoptysis and recurrent alveolar hemorrhage. The combination of IPH and celiac disease (CD) is extremely rare. We report a 9-year-old boy with Lane-Hamilton syndrome, co-occurrence of pulmonary hemosiderosis with CD. This presentation is unique presentation because he has also retinal pigmentation. PMID:21337729

  8. The Degenerative Spine.

    PubMed

    Clarençon, Frédéric; Law-Ye, Bruno; Bienvenot, Peggy; Cormier, Évelyne; Chiras, Jacques

    2016-08-01

    Degenerative disease of the spine is a leading cause of back pain and radiculopathy, and is a frequent indication for spine MR imaging. Disc degeneration, disc protrusion/herniation, discarhtrosis, spinal canal stenosis, and facet joint arthrosis, as well as interspinous processes arthrosis, may require an MR imaging workup. This review presents the MR imaging patterns of these diseases and describes the benefit of the MR imaging in these indications compared with the other imaging modalities like plain radiographs or computed tomography scan. PMID:27417397

  9. Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series

    PubMed Central

    Hauser, Ross A.; Orlofsky, Amos

    2013-01-01

    Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation. PMID:24046512

  10. Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease.

    PubMed

    Li, Ling-Jun; Ikram, Mohammad Kamran; Wong, Tien Yin

    2016-04-15

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non-invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low-fibre and high-sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre-clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood. PMID:26435039

  11. Nutrition and retinal degenerations.

    PubMed

    Berson, E L

    2000-01-01

    Considerable progress has been made in the understanding and management of degenerative diseases of the retina involving photoreceptors. Nutritional approaches to treatment have proved successful in the case of the common forms of retinitis pigmentosa (supplementation with vitamin A), Bassen-Kornzweig disease (supplementation with vitamins A, E, and K), gyrate atrophy (low-protein, low-arginine diet and/or supplementation with vitamin B6), and Refsum disease (low-phytol, low-phytanic acid diet). The night blindness associated with Sorsby fundus dystrophy can be reversed over the short term with vitamin A. A significant trend for decreased risk for advanced or exudative ARMD has been reported among those whose diets contain a higher content of carotenoids, such as spinach and collard greens. A randomized trial is in progress to determine whether beta-carotene, vitamin C, and vitamin E as well as trace minerals, particularly zinc, will modify the course of ARMD. The difficulties that patients with retinal degenerations face as a result of their diminishing vision, sometimes over decades, cannot be underestimated. Nutritional therapy has proved effective in modifying the course of a number of these conditions; the therapeutic benefit of nutritional modification in diseases that have a genetic basis is of particular interest. Further research is warranted to determine the mechanisms by which these treatments provide their benefit as well as to identify other conditions that may yield to nutritional intervention. Risk-factor analyses of well-defined populations followed over time with food-frequency questionnaires in conjunction with careful assessments of visual function may reveal other dietary constituents that can modify the course of degenerative diseases of the retina. PMID:11064860

  12. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  13. Optical coherence tomography and electrophysiology of retinal and visual pathways in Wilson's disease.

    PubMed

    Langwińska-Wośko, Ewa; Litwin, Tomasz; Szulborski, Kamil; Członkowska, Anna

    2016-04-01

    We evaluated correlations between positive findings of changes on brain magnetic resonance imaging (MRI) and selected morphological and electrophysiological parameters of the retinal and visual systems in Wilson's disease. Fifty-eight Wilson's disease symptomatic patients were divided according to whether they displayed brain changes on MRI (positive, n = 39; negative, n = 19). All participants and healthy control group (n = 30), underwent retinal optical coherence tomography to assess the thickness of macula and the total retinal nerve fiber layer. Visual evoked potentials were measured and electroretinography was performed. Macular and retinal nerve fibers were thinner in participants with changes on MRI than in participants without changes. Electrophysiological parameters were markedly different in the MRI positive group compared with the negative group and 30 healthy controls; however, some abnormalities were evident in cases without visible brain pathology. Morphological and electrophysiological changes of retinal and visual pathways are associated with MRI visualized brain injury in Wilson's disease and may be useful for detecting the degree of neurodegeneration. PMID:26686677

  14. The Self-Concept of Spanish Young Adults with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Lopez-Justicia, Maria Dolores; Cordoba, Inmaculada Nieto

    2006-01-01

    Retinitis pigmentosa (RP) is a degenerative disease of the retina that causes the severe impairment of visual functioning similar to low vision, leading, in many cases, to blindness. Because the construct of self-concept plays a key role in personality, this study was designed to measure self-concept in a group of young adults with RP. The…

  15. Common pathways in health benefit properties of RSV in cardiovascular diseases, cancers and degenerative pathologies.

    PubMed

    Aires, Virginie; Delmas, Dominique

    2015-01-01

    Lots of epidemiological studies have put forward the beneficial effects of dietary polyphenols consumption in the prevention of diseases related to aging i.e vascular pathologies, neurodegeneration, cancers and associated inflammatory processes. Among polyphenols, resveratrol (trans-3,4',5- trihydroxystilbene, RSV), a naturally occurring stilbene widely distributed in foodstuffs such as grapes and wine, has been the most studied. Researches performed since the last decades in vitro, in animal models and in (pre)clinical studies have pointed out its pleiotropic health benefits by acting on multiple signaling pathways which go beyond its originally described direct antioxidant activity. However, its low bioavailability upon oral ingestion and lack of specificity may hamper the translation of the encouraging experimental data into human health benefits. Herein we provide an overview on the capacity of RSV to regulate oxidative stress-induced signaling and to modulate key components of signal transduction pathways which are commonly altered in cardiovascular, neurodegenerative and cancer pathologies. We also have attempted to provide a comprehensive outlook on RSV metabolism and biological activity of its main metabolites and discussed about the new strategies developed to circumvent its poor bioavailability and to improve its therapeutic efficacy, including synthesis of new derivatives and new formulations for its cell delivery. PMID:25601605

  16. Hsp90 as a Potential Therapeutic Target in Retinal Disease.

    PubMed

    Aguilà, Mònica; Cheetham, Michael E

    2016-01-01

    The molecular chaperone heat shock protein 90 (Hsp90) is a pivotal cellular regulator involved in the folding, activation and assembly of a wide range of proteins. Hsp90 has multiple roles in the retina and the use of different Hsp90 inhibitors has been shown to prevent retinal degeneration in models of retinitis pigmentosa and age-related macular degeneration. Hsp90 is also a potential target in uveal melanoma. Mechanistically, Hsp90 inhibition can evoke a dual response in the retina; stimulating a stress response with molecular chaperone expression. Thereby leading to an improvement in visual function and photoreceptor survival; however, prolonged inhibition can also stimulate the degradation of Hsp90 client proteins potentially deleteriously affect vision. Here, we review the multiple roles of Hsp90 in the retina and the therapeutic potential of Hsp90 as a target. PMID:26427407

  17. Vitrectomy for Tractional Retinal Detachment with Twin Retinal Capillary Hemangiomas in a Patient with Von Hippel-Lindau Disease: A Case Report

    PubMed Central

    Suzuki, Hiroyuki; Kakurai, Keigo; Morishita, Seita; Kimura, Daisaku; Fukumoto, Masanori; Sato, Takaki; Kida, Teruyo; Ueki, Mari; Sugasawa, Jun; Ikeda, Tsunehiko

    2016-01-01

    Purpose The purpose of this study was to report a case of Von Hippel-Lindau disease (VHL) with twin retinal capillary hemangiomas that was successfully treated by vitreous surgery for tractional retinal detachment following laser photocoagulation. Case A 44-year-old male presented at our university hospital after noticing decreased visual acuity in his right eye. The patient had previously undergone multiple operations for cerebellar, thoracic, and lumbar spine hemangioblastomas when he was approximately 19 years old. Upon initial examination, ocular findings revealed twin connected retinal capillary hemangiomas around the temporal upper area of the patient's right eye. The patient was subsequently diagnosed with VHL based on his medical history and current observations of the ocular fundus. Tractional retinal detachment had occurred as the result of the formation of proliferative membranes following laser photocoagulation. The patient underwent vitreous surgery to treat the tractional retinal detachment, resulting in a successful postoperative outcome. Conclusion The findings of this study show the possibility that proliferative changes and tractional retinal detachment can arise following photocoagulation for retinal capillary hemangiomas in patients with VHL. PMID:27462263

  18. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects

    PubMed Central

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease. PMID:26885185

  19. Deciphering Structural Intermediates and Genotoxic Fibrillar Aggregates of Albumins: A Molecular Mechanism Underlying for Degenerative Diseases

    PubMed Central

    Naeem, Aabgeena; Amani, Samreen

    2013-01-01

    The misfolding and aggregation of proteins is involved in some of the most prevalent neurodegenerative disorders. The importance of human serum albumin (HSA) stems from the fact that it is involved in bio-regulatory and transport phenomena. Here the effect of acetonitrile (ACN) on the conformational stability of HSA and by comparison, ovalbumin (OVA) has been evaluated in the presence and absence of NaCl. The results show the presence of significant amount of secondary structure in HSA at 70% ACN and in OVA at 50% ACN, as evident from far-UV Circular Dichroism (CD) and Attenuated Total Reflection Fourier transformed infra red spectroscopy (ATR-FTIR). Tryptophan and 8-Anilino-1-Naphthalene-Sulphonic acid (ANS) fluorescence indicate altered tryptophan environment and high ANS binding suggesting a compact “molten globule”-like conformation with enhanced exposure of hydrophobic surface area. However, in presence of NaCl no intermediate state was observed. Detection of aggregates in HSA and OVA was possible at 90% ACN. Aggregates possess extensive β-sheet structure as revealed by far-UV CD and ATR-FTIR. These aggregates exhibit increase Thioflavin T (Th T) fluorescence with a red shift of Congo red (CR) absorption spectrum. X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) analysis confirmed the presence of fibrillar aggregates. Single cell gel electrophoresis (SCGE) assay of these fibrillar aggregates showed the DNA damage resulting in cell necrosis confirming their genotoxic nature. Some proteins not related to any human disease form fibrils in vitro. In the present study ACN gives access to a model system to study the process of aggregation. PMID:23342075

  20. Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

    PubMed Central

    Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

    2015-01-01

    Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

  1. Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up

    PubMed Central

    Ohta, Hideki; Matsumoto, Yoshiyuki; Morishita, Yuichirou; Sakai, Tsubasa; Huang, George; Kida, Hirotaka; Takemitsu, Yoshiharu

    2011-01-01

    Background When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. Methods The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. Results The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. Conclusions Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future. PMID:25802671

  2. Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data

    PubMed Central

    Moriguchi, Yu; Alimi, Marjan; Khair, Thamina; Manolarakis, George; Berlin, Connor; Bonassar, Lawrence J.; Härtl, Roger

    2016-01-01

    Study Design  Literature review. Objective  Degenerative disk disease (DDD) has a negative impact on quality of life and is a major cause of morbidity worldwide. There has been a growing interest in the biological repair of DDD by both researchers and clinicians alike. To generate an overview of the recent progress in reparative strategies for the treatment of DDD highlighting their promises and limitations, a comprehensive review of the current literature was performed elucidating data from in vivo animal and clinical studies. Methods  Articles and abstracts available in electronic databases of PubMed, Web of Science, and Google Scholar as of December 2014 were reviewed. Additionally, data from unpublished, ongoing clinical trials was retrieved from clinicaltrials.gov and available abstracts from research forums. Data was extracted from the most recent in vivo animal or clinical studies involving any of the following: (1) treatment with biomolecules, cells, or tissue-engineered constructs and (2) annulus fibrosus repair. Results  Seventy-five articles met the inclusion criteria for review. Among these, 17 studies involved humans; 37, small quadrupeds; and 21, large quadrupeds. Findings from all treatments employed demonstrated improvement either in regenerative capacity or in pain attenuation, with the exception of one clinical study. Conclusion  Published clinical studies on cell therapy have reported encouraging results in the treatment of DDD and resultant back pain. We expect new data to emerge in the near future as treatments for DDD continue to evolve in parallel to our greater understanding of disk health and pathology. PMID:27433434

  3. One decade follow up after nucleoplasty in the management of degenerative disc disease causing low back pain and radiculopathy

    PubMed Central

    Cincu, Rafael; Lorente, Francisco de Asis; Gomez, Joaquin; Eiras, Jose; Agrawal, Amit

    2015-01-01

    Objectives: Nucleoplasty is a minimally invasive procedure that is developed to treat patients with symptomatic, but contained disc herniations or bulging discs. The purpose of this study was to evaluate a decade follow-up of coblation nucleoplasty treatment for protruded lumbar intervertebral disc. Methods: In this retrospective study there a total 50 patients who underwent intradiscal coblation therapy for symptomatic, but contained lumbar degenerative disc disease were included. Relief of low back pain, leg pain and numbness after the operation were assessed by visual analog pain scale (VAS). Function of lower limb and daily living of patients were evaluated by the Oswestry disability index (ODI) and subjective global rating of overall satisfaction were recorded and analyzed. Results: There were 27 male and 23 female with followup mean follow up of 115 months (range 105–130 months) with a mean age was 52 years (range 26–74 years). Analgesic consumption was reduced or stopped in 90% of these cases after 1 year. At 24 months follow up VAS was four points and ODI was 7.2. In three patients, we repeated the cool ablation after 36 months, at L3–4 level in two cases. Ten patients continue to be asymptomatic after 114 months of intervention. There were no complications with the procedure including nerve root injury, discitis or allergic reactions. Conclusions: Nucleoplasty may provide intermittent relief in contained disc herniation without significant complications and minimal morbidity. In accordance with the literature the evidence for intradiscal coablation therapy is moderate in managing chronic discogenic low back pain; nucleoplasty appears to be safe and effective. PMID:25767571

  4. Hybrid surgery versus anterior cervical discectomy and fusion for multilevel cervical degenerative disc diseases: a meta-analysis

    PubMed Central

    Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long

    2015-01-01

    The objective of this meta-analysis is to compare hybrid surgery (HS) and cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc diseases (DDD). Systematic searches of all published studies through March 2015 were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs involving HS and ACDF for multilevel DDD were included. All literature was searched and assessed by two independent reviewers according to the standard of Cochrane systematic review. Data of functional and radiological outcomes in two groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis revealed significant differences in blood loss (p = 0.005), postoperative C2–C7 ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group. No significant differences were found regarding operation time (p = 0.75), postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups. Hybrid surgery demonstrated excellent clinical efficacy and radiological results. Postoperative C2–C7 ROM was closer to the physiological status. No decrease in the ROM of the adjacent segment was noted in the hybrid surgery group. PMID:26307360

  5. Retinal Disorders

    MedlinePlus

    ... be serious enough to cause blindness. Examples are Macular degeneration - a disease that destroys your sharp, central vision Diabetic eye disease Retinal detachment - a medical emergency, when the retina is ... children. Macular pucker - scar tissue on the macula Macular hole - ...

  6. Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

    PubMed Central

    Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN

    2013-01-01

    Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

  7. Melanopsin retinal ganglion cell loss and circadian dysfunction in Alzheimer's disease (Review)

    PubMed Central

    FENG, RUIQI; LI, LIJUAN; YU, HAIYAN; LIU, MIN; ZHAO, WEI

    2016-01-01

    Alzheimer's disease affects 27 million individuals and is the most common cause of dementia worldwide. The pathology of Alzheimer's disease is primarily due to the β-amyloid deposits and neurofibrillary tangles. These deposits exist largely in the cerebral blood vessels, but have also been shown to exist in retinal vessels. A new class of cells that were recently identified, known as melanopsin-expressing retinal ganglion cells (mRGCs), are involved in the non-image forming functions of the eye. These functions include circadian activities such as temperature rhythms, melatonin release and rest-activity cycles. Circadian dysfunction has been investigated in many cases of Alzheimer's disease. In this review, we outline the current accepted Alzheimer's disease pathology, the role of mRCGs in optic neuropathies and the role of mRCGs, leading to circadian dysfunction, in Alzheimer's disease. PMID:26935586

  8. A Method for the Isolation and Culture of Adult Rat Retinal Pigment Epithelial (RPE) Cells to Study Retinal Diseases

    PubMed Central

    Heller, Janosch P.; Kwok, Jessica C. F.; Vecino, Elena; Martin, Keith R.; Fawcett, James W.

    2015-01-01

    Diseases such as age-related macular degeneration (AMD) affect the retinal pigment epithelium (RPE) and lead to the death of the epithelial cells and ultimately blindness. RPE transplantation is currently a major focus of eye research and clinical trials using human stem cell-derived RPE cells are ongoing. However, it remains to be established to which extent the source of RPE cells for transplantation affects their therapeutic efficacy and this needs to be explored in animal models. Autotransplantation of RPE cells has attractions as a therapy, but existing protocols to isolate adult RPE cells from rodents are technically difficult, time-consuming, have a low yield and are not optimized for long-term cell culturing. Here, we report a newly devised protocol which facilitates reliable and simple isolation and culture of RPE cells from adult rats. Incubation of a whole rat eyeball in 20 U/ml papain solution for 50 min yielded 4 × 104 viable RPE cells. These cells were hexagonal and pigmented upon culture. Using immunostaining, we demonstrated that the cells expressed RPE cell-specific marker proteins including cytokeratin 18 and RPE65, similar to RPE cells in vivo. Additionally, the cells were able to produce and secrete Bruch’s membrane matrix components similar to in vivo situation. Similarly, the cultured RPE cells adhered to isolated Bruch’s membrane as has previously been reported. Therefore, the protocol described in this article provides an efficient method for the rapid and easy isolation of high quantities of adult rat RPE cells. This provides a reliable platform for studying the therapeutic targets, testing the effects of drugs in a preclinical setup and to perform in vitro and in vivo transplantation experiments to study retinal diseases. PMID:26635529

  9. The clinical features of retinal disease due to a dominant mutation in RPE65

    PubMed Central

    Hull, Sarah; Mukherjee, Rajarshi; Holder, Graham E.; Moore, Anthony T.

    2016-01-01

    Purpose To present a detailed phenotypic and molecular study of two families with autosomal dominant RPE65-related retinal dystrophy. Methods Five patients from two families were ascertained from the retinal clinics of a tertiary referral center. Phenotyping included retinal imaging and electrophysiological testing. Bidirectional Sanger sequencing of exon 13 of RPE65 and its intron–exon boundaries was performed on all reported patients and segregation confirmed in available relatives. The main outcome measures were the results of an ophthalmic examination and investigation and molecular genetic analysis. Results Four affected patients from two families presented with nyctalopia and central visual disturbance in adulthood progressing to severe visual loss by the fifth to eighth decades. The patients had extensive chorioretinal atrophy with a relatively preserved anterior retina. In the second family, one patient had bilateral, vitelliform-like foveal lesions consistent with adult onset vitelliform macular dystrophy and no peripheral retinal changes. These unrelated families were both heterozygous for c.1430A>G (p.Asp477Gly). One unaffected family member also tested positive for this mutation but had good vision at age 80 years. Conclusions Autosomal dominant retinal dystrophy resembling choroideremia can arise from a heterozygous mutation in RPE65. It may manifest with mild disease or be non-penetrant. Awareness of these unusual presentations can facilitate targeted molecular investigation. PMID:27307694

  10. A Probabilistic Framework for Content-Based Diagnosis of Retinal Disease

    SciTech Connect

    Tobin Jr, Kenneth William; Abdelrahman, Mohamed A; Chaum, Edward; Muthusamy Govindasamy, Vijaya Priya; Karnowski, Thomas Paul

    2007-01-01

    Diabetic retinopathy is the leading cause of blindness in the working age population around the world. Computer assisted analysis has the potential to assist in the early detection of diabetes by regular screening of large populations. The widespread availability of digital fundus cameras today is resulting in the accumulation of large image archives of diagnosed patient data that captures historical knowledge of retinal pathology. Through this research we are developing a content-based image retrieval method to verify our hypothesis that retinal pathology can be identified and quantified from visually similar retinal images in an image archive. We will present diagnostic results for specificity and sensitivity on a population of 395 fundus images representing the normal fundus and 14 stratified disease states.

  11. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOEpatents

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  12. Canine degenerative myelopathy.

    PubMed

    Coates, Joan R; Wininger, Fred A

    2010-09-01

    Canine degenerative myelopathy (DM) is an adult-onset fatal neurodegenerative disease that occurs in many breeds. The initial upper motor neuron spastic paraparesis and general proprioceptive ataxia in the pelvic limbs progress to a flaccid lower motor neuron tetraparesis. Recently, a missense mutation in the superoxide dismutase 1 (SOD1) gene was found to be a risk factor for DM, suggesting that DM is similar to some forms of human amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This article reviews the current knowledge of canine DM with regard to its signalment, clinical spectrum, diagnostic approach, and treatment. The implications of the SOD1 mutation on both diseases are discussed, comparing pathogenic mechanisms while conveying perspectives to translational medicine. PMID:20732599

  13. Structural Studies on Acetylcholinesterase and Paraoxonase Directed Towards Development of Therapeutic Biomolecules for the Treatment of Degenerative Diseases and Protection Against Chemical Threat Agents

    NASA Astrophysics Data System (ADS)

    Sussman, Joel L.; Silman, Israel

    Acetylcholinesterase and paraoxonase are important targets for treatment of degenerative diseases, Alzheimer's disease and atherosclerosis, respectively, both of which impose major burdens on the health care systems in Western society. Acetylcholinesterase is the target of lethal nerve agents, and paraoxonase is under consideration as a bioscavenger for their detoxification. Both are thus the subject of research and development in the context of nerve agent toxicology. The crystal structures of the two enzymes are described, and structure/function relationships are discussed in the context of drug development and of development of means of protection against chemical threats.

  14. Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

    PubMed Central

    Acland, Gregory M.

    2014-01-01

    Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

  15. Relationship between Retinal Vascular Caliber and Coronary Artery Disease in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

    PubMed Central

    Josef, Pikkel; Ali, Ibrahim; Ariel, Prober; Alon, Marmor; Nimer, Assy

    2013-01-01

    Objective: To evaluate the relationship between retinal vascular caliber and cardiovascular disease in non-alcoholic fatty liver disease (NAFLD) patients without diabetes and hypertension. Methods: Intention to treat study of individuals who underwent cardiac computed tomography (CT) during a two year period. Coronary artery disease (CAD) was defined as stenosis of >50% in at least one major coronary artery. Liver and spleen density were measured by abdominal (CT); intima-media thickness (IMT) by Doppler ultrasound; retinal artery and vein diameter by colored-retinal angiography; and metabolic syndrome by ATP III guidelines. Serum biomarkers of insulin resistance, inflammation, and oxidant-antioxidant status were assessed. Results: Compared with 22 gender and age matched controls, the 29 NAFLD patients showed higher prevalence of coronary plaques (70% vs. 30%, p < 0.001), higher prevalence of coronary stenosis (30% vs. 15%, p < 0.001), lower retinal arteriole-to-venule ratio (AVR) (0.66 ± 0.06 vs. 0.71 ± 0.02, p < 0.01), higher IMT (0.98 ± 0.3 vs. 0.83 ± 0.1, p < 0.04), higher carotid plaques (60% vs. 40%, p < 0.001), higher homeostasis model assessment of insulin resistance (HOMA) (4.0 ± 3.4 vs. 2.0 ± 1.0, p < 0.005), and higher triglyceride levels (200 ± 80 vs. 150 ± 60, p < 0.005) than controls. Multivariate analysis showed fatty liver (OR 2.5; p < 0.01), IMT (OR 2.3 p < 0.001), and retinal AVR ratio (OR 1.5, p < 0.01) to be strongly associated with CAD independent of metabolic syndrome (OR 1.2, p < 0.05). Conclusions: Patients with smaller retinal AVR (<0.7) are likely to be at increased risk for CAD and carotid atherosclerosis in patients with NAFLD even without hypertension or diabetes. PMID:23924883

  16. Reprogramming of adult rod photoreceptors prevents retinal degeneration

    PubMed Central

    Montana, Cynthia L.; Kolesnikov, Alexander V.; Shen, Susan Q.; Myers, Connie A.; Kefalov, Vladimir J.; Corbo, Joseph C.

    2013-01-01

    A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration. PMID:23319618

  17. The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease

    PubMed Central

    Sidman, Richard L.; Li, Jianxue; Lawrence, Matthew; Hu, Wenzheng; Musso, Gary F.; Giordano, Ricardo J.; Cardó-Vila, Marina; Pasqualini, Renata; Arap, Wadih

    2016-01-01

    Blood vessel growth from preexisting vessels (angiogenesis) underlies many severe diseases including major blinding retinal diseases such as retinopathy of prematurity (ROP) and aged macular degeneration (AMD). This observation has driven development of antibody inhibitors that block a central factor in AMD, named vascular endothelial growth factor (VEGF), from binding to its receptors VEGFR-1 and VEGFR-2. However, some patients are insensitive to current anti-VEGF drugs or develop resistance, and the required repeated intravitreal injection of these large molecules is costly and clinically problematic. Here, we have evaluated a small cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys), abbreviated as D(CLPRC), and hereafter named Vasotide, that inhibits retinal angiogenesis by binding selectively to the VEGF receptors, VEGFR-1 and Neuropilin-1 (NRP-1). Delivery of Vasotide in eye drops or via intraperitoneal injection in a laser-induced monkey model of human wet AMD, a mouse genetic knockout model of the AMD subtype called retinal angiomatous proliferation (RAP), and a mouse oxygen-induced model of retinopathy of prematurity (ROP) markedly decreased retinal angiogenesis in all three animal models. This prototype drug candidate is a promising new dual receptor inhibitor of the VEGF ligand with potential for translation into safer, less invasive applications to combat pathological angiogenesis in retinal disorders. PMID:26468327

  18. Portable retinal imaging for eye disease screening using a consumer-grade digital camera

    NASA Astrophysics Data System (ADS)

    Barriga, Simon; Larichev, Andrey; Zamora, Gilberto; Soliz, Peter

    2012-03-01

    The development of affordable means to image the retina is an important step toward the implementation of eye disease screening programs. In this paper we present the i-RxCam, a low-cost, hand-held, retinal camera for widespread applications such as tele-retinal screening for eye diseases like diabetic retinopathy (DR), glaucoma, and age-related ocular diseases. Existing portable retinal imagers do not meet the requirements of a low-cost camera with sufficient technical capabilities (field of view, image quality, portability, battery power, and ease-of-use) to be distributed widely to low volume clinics, such as the offices of single primary care physicians serving rural communities. The i-RxCam uses a Nikon D3100 digital camera body. The camera has a CMOS sensor with 14.8 million pixels. We use a 50mm focal lens that gives a retinal field of view of 45 degrees. The internal autofocus can compensate for about 2D (diopters) of focusing error. The light source is an LED produced by Philips with a linear emitting area that is transformed using a light pipe to the optimal shape at the eye pupil, an annulus. To eliminate corneal reflex we use a polarization technique in which the light passes through a nano-wire polarizer plate. This is a novel type of polarizer featuring high polarization separation (contrast ratio of more than 1000) and very large acceptance angle (>45 degrees). The i-RxCam approach will yield a significantly more economical retinal imaging device that would allow mass screening of the at-risk population.

  19. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma.

    PubMed

    Zhang, Kang; Zhang, Liangfang; Weinreb, Robert N

    2012-07-01

    Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities. PMID:22699774

  20. Retinal Remodeling: Concerns, Emerging Remedies and Future Prospects

    PubMed Central

    Krishnamoorthy, Vidhyasankar; Cherukuri, Pitchaiah; Poria, Deepak; Goel, Manvi; Dagar, Sushma; Dhingra, Narender K.

    2016-01-01

    Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Müller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs), the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed “retinal remodeling”, pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies. PMID:26924962

  1. Clinical and radiologic comparison of dynamic cervical implant arthroplasty versus anterior cervical discectomy and fusion for the treatment of cervical degenerative disc disease.

    PubMed

    Li, Zhonghai; Yu, Shunzhi; Zhao, Yantao; Hou, Shuxun; Fu, Qiang; Li, Fengning; Hou, Tiesheng; Zhong, Hongbin

    2014-06-01

    This study compared the clinical and radiological outcomes of dynamic cervical implant (DCI; Scient'x, Villers-Bretonneux, France) arthroplasty versus anterior cervical discectomy and fusion (ACDF) for the treatment of cervical degenerative disc disease. This prospective cohort study enrolled patients with single-level cervical degenerative disc disease who underwent DCI arthroplasty or ACDF between September 2009 and June 2011. Patients were followed up for more than 2years. Clinical evaluation included the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Neck Disability Index (NDI), Japan Orthopedic Association (JOA) score, and visual analog scale (VAS) scores for neck and arm pain. Radiological assessments included segmental range of motion (ROM), overall ROM (C2-C7), disc height (DHI), and changes in adjacent disc spaces. The VAS, SF-36, JOA, and NDI scores improved significantly after surgery in both the DCI and ACDF groups. The VAS, JOA, and SF-36 scores were not significantly different between the DCI and ACDF groups at the final follow-up. The segmental ROM at the treated level and overall ROM increased significantly after surgery in the DCI group, but the ROM in the adjacent cephalad and caudal segments did not change significantly. The mean DHI at the treated level was significantly restored after surgery in both groups. Five patients (12.8%) in the DCI group showed new signs of adjacent segment degeneration. These results indicate that DCI is an effective, reliable, and safe procedure for the treatment of cervical degenerative disc disease. However, there is no definitive evidence that DCI arthroplasty has better intermediate-term results than ACDF. PMID:24411326

  2. Percutaneous Transforaminal Lumbar Interbody Fusion (pTLIF) with a Posterolateral Approach for the Treatment of Degenerative Disk Disease: Feasibility and Preliminary Results

    PubMed Central

    Morgenstern, Christian

    2015-01-01

    Background Interbody fusion by open discectomy is the usual treatment for degenerative disk disease but requires a relatively long recovery period. The transforaminal posterolateral approach is a well-known standard in endoscopic spine surgery that allows direct access to the disk with progressive tissue dilation. The aim of this study was to assess the feasibility of percutaneous transforaminal interbody fusion (pTLIF) with insertion of an expandable or a standard rigid interbody implant for patients with degenerative disk disease with or without spondylolisthesis and for revision surgery. Methods Between 2009 and 2014, the pTLIF procedure was performed in 30 patients. Ten patients underwent insertion of a rigid implant (group A) and the remaining 20 underwent insertion of an expandable titanium interbody implant as the initial procedure (n = 10) (group B) or after failed back surgery (n = 10) (group C). Patient outcomes were scored with visual analogic scale (VAS), Oswestry disability index (ODI) and modified Macnab criteria. Results The mean follow-up period was 38 (17) (range 11 to 67) months. The outcome was excellent in 18, good in 10 and fair in 2. No poor results and no major complications were reported. No differences in VAS and ODI scores according to the study group were found. Median postoperative time until hospital discharge was 26 hours (20 to 68 hours). Postoperative values for VAS and ODI scores improved significantly (p<0.05) compared to preoperative data in all study groups. Conclusions These preliminary results have shown the feasibility and efficacy of the pTLIF procedure using a posterolateral approach for the treatment of degenerative disk disease with or without spondylolisthesis up to grade 2 and in revision surgery. No significant differences in outcome were observed between an expandable and a rigid cage. Median postoperative time until hospital discharge was faster compared to standard TLIF (26 hours vs. 9.3 days). PMID:26484004

  3. N-acetylcysteine amide (NACA) prevents retinal degeneration by up-regulating reduced glutathione production and reversing lipid peroxidation.

    PubMed

    Schimel, Andrew M; Abraham, Linu; Cox, Douglas; Sene, Abdoulaye; Kraus, Courtney; Dace, Dru S; Ercal, Nuran; Apte, Rajendra S

    2011-05-01

    Oxidative stress plays a critical role in accelerating retinal pigment epithelial dysfunction and death in degenerative retinal diseases, including age-related macular degeneration. Given the key role of oxidative stress-induced retinal pigment epithelial cell death and secondary photoreceptor loss in the pathogenesis of age-related macular degeneration, we hypothesized that a novel thiol antioxidant, N-acetylcysteine amide (NACA), might ameliorate cellular damage and subsequent loss of vision. Treatment of human retinal pigment epithelial cells with NACA protected against oxidative stress-induced cellular injury and death. NACA acted mechanistically by scavenging existing reactive oxygen species while halting production of reactive oxygen species by reversing lipid peroxidation. Furthermore, NACA functioned by increasing the levels of reduced glutathione and the phase II detoxification enzyme glutathione peroxidase. Treatment of mice exposed to phototoxic doses of light with NACA maintained retinal pigment epithelial cell integrity and prevented outer nuclear layer cell death as examined by histopathologic methods and rescued photoreceptor function as measured by electroretinography. These observations indicate that NACA protects against oxidative stress-induced retinal pigment epithelial and photoreceptor cell death in vitro and in vivo. The data suggest that NACA may be a novel treatment in rescuing retinal function and preventing vision loss secondary to retinal degenerative diseases, including age-related macular degeneration. PMID:21457933

  4. N-Acetylcysteine Amide (NACA) Prevents Retinal Degeneration by Up-Regulating Reduced Glutathione Production and Reversing Lipid Peroxidation

    PubMed Central

    Schimel, Andrew M.; Abraham, Linu; Cox, Douglas; Sene, Abdoulaye; Kraus, Courtney; Dace, Dru S.; Ercal, Nuran; Apte, Rajendra S.

    2011-01-01

    Oxidative stress plays a critical role in accelerating retinal pigment epithelial dysfunction and death in degenerative retinal diseases, including age-related macular degeneration. Given the key role of oxidative stress–induced retinal pigment epithelial cell death and secondary photoreceptor loss in the pathogenesis of age-related macular degeneration, we hypothesized that a novel thiol antioxidant, N-acetylcysteine amide (NACA), might ameliorate cellular damage and subsequent loss of vision. Treatment of human retinal pigment epithelial cells with NACA protected against oxidative stress–induced cellular injury and death. NACA acted mechanistically by scavenging existing reactive oxygen species while halting production of reactive oxygen species by reversing lipid peroxidation. Furthermore, NACA functioned by increasing the levels of reduced glutathione and the phase II detoxification enzyme glutathione peroxidase. Treatment of mice exposed to phototoxic doses of light with NACA maintained retinal pigment epithelial cell integrity and prevented outer nuclear layer cell death as examined by histopathologic methods and rescued photoreceptor function as measured by electroretinography. These observations indicate that NACA protects against oxidative stress–induced retinal pigment epithelial and photoreceptor cell death in vitro and in vivo. The data suggest that NACA may be a novel treatment in rescuing retinal function and preventing vision loss secondary to retinal degenerative diseases, including age-related macular degeneration. PMID:21457933

  5. Features specific to retinal pigment epithelium cells derived from three-dimensional human embryonic stem cell cultures — a new donor for cell therapy

    PubMed Central

    Li, Zhengya; Li, Qiyou; Xu, Haiwei; Yin, Zheng Qin

    2016-01-01

    Retinal pigment epithelium (RPE) transplantation is a particularly promising treatment of retinal degenerative diseases affecting RPE-photoreceptor complex. Embryonic stem cells (ESCs) provide an abundant donor source for RPE transplantation. Herein, we studied the time-course characteristics of RPE cells derived from three-dimensional human ESCs cultures (3D-RPE). We showed that 3D-RPE cells possessed morphology, ultrastructure, gene expression profile, and functions of authentic RPE. As differentiation proceeded, 3D-RPE cells could mature gradually with decreasing proliferation but increasing functions. Besides, 3D-RPE cells could form polarized monolayer with functional tight junction and gap junction. When grafted into the subretinal space of Royal College of Surgeons rats, 3D-RPE cells were safe and efficient to rescue retinal degeneration. This study showed that 3D-RPE cells were a new donor for cell therapy of retinal degenerative diseases. PMID:27009841

  6. Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease

    PubMed Central

    Frost, S; Kanagasingam, Y; Sohrabi, H; Vignarajan, J; Bourgeat, P; Salvado, O; Villemagne, V; Rowe, C C; Lance Macaulay, S; Szoeke, C; Ellis, K A; Ames, D; Masters, C L; Rainey-Smith, S; Martins, R N

    2013-01-01

    The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P=0.01 and P=0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments. PMID:23443359

  7. Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.

    2014-01-01

    Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  8. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  9. Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease

    PubMed Central

    Ghiasvand, Noor M.; Rudolph, Dellaney D.; Mashayekhi, Mohammad; Brzezinski, Joseph A.; Goldman, Daniel; Glaser, Tom

    2011-01-01

    Individuals with nonsyndromic congenital retinal nonattachment (NCRNA) are totally blind from birth. The disease afflicts ~1% of Kurdish people living in a group of neighboring villages in North Khorasan, Iran. We show NCRNA is caused by a 6523bp deletion that spans a remote cis regulatory element 20 kb upstream from ATOH7 (Math5), a bHLH transcription factor gene required for retinal ganglion cell (RGC) and optic nerve development. In humans, the absence of RGCs stimulates massive neovascular growth of fetal blood vessels within the vitreous, and early retinal detachment. The remote ATOH7 element appears to act as a secondary or ‘shadow’ transcriptional enhancer. It has minimal sequence similarity to the primary enhancer, which is close to the Atoh7 promoter, but drives transgene expression with an identical spatiotemporal pattern in the mouse retina. The human transgene also functions in zebrafish, reflecting deep evolutionary conservation. These dual enhancers may reinforce Atoh7 expression during early critical stages of eye development when retinal neurogenesis is initiated. PMID:21441919

  10. Pseudotumoral and Multiple Retinal Pigment Epithelium Proliferation in Vogt-Koyanagi-Harada Disease.

    PubMed

    Yepez, Juan B; Murati, Felipe; Petitto, Michele; Arevalo, J Fernando

    2015-01-01

    We report a case of pseudotumoral retinal pigment epithelium (RPE) proliferation in Vogt-Koyanagi-Harada (VKH) disease, in a 50-year-old female who presented with a juxtapapillary and peripheral subretinal hyperpigmented lesions in the left eye and "sunset glow fundus," hyperpigmented striae, and multiple atrophic chorioretinal spots in the periphery. The darkly pigmented exuberant larger subretinal mass extended to the periphery with associated subretinal fibrosis. This patient demonstrated the entire clinical presentation of VKH disease, which tends to course with a chronic, bilateral, granulomatous panuveitis and exudative retinal detachment associated with poliosis, vitiligo, alopecia, and central nervous system and auditory signs. Our case is unique for the presence of exuberant, pseudotumoral RPE proliferation at the juxtapapillary region and peripheral area. Although this complication has rarely been reported, a high index of suspicion is warranted for early diagnosis and avoids unnecessary treatments of a pseudotumor. PMID:26509089

  11. Pseudotumoral and Multiple Retinal Pigment Epithelium Proliferation in Vogt-Koyanagi-Harada Disease

    PubMed Central

    Yepez, Juan B.; Murati, Felipe; Petitto, Michele; Arevalo, J. Fernando

    2015-01-01

    We report a case of pseudotumoral retinal pigment epithelium (RPE) proliferation in Vogt-Koyanagi-Harada (VKH) disease, in a 50-year-old female who presented with a juxtapapillary and peripheral subretinal hyperpigmented lesions in the left eye and “sunset glow fundus,” hyperpigmented striae, and multiple atrophic chorioretinal spots in the periphery. The darkly pigmented exuberant larger subretinal mass extended to the periphery with associated subretinal fibrosis. This patient demonstrated the entire clinical presentation of VKH disease, which tends to course with a chronic, bilateral, granulomatous panuveitis and exudative retinal detachment associated with poliosis, vitiligo, alopecia, and central nervous system and auditory signs. Our case is unique for the presence of exuberant, pseudotumoral RPE proliferation at the juxtapapillary region and peripheral area. Although this complication has rarely been reported, a high index of suspicion is warranted for early diagnosis and avoids unnecessary treatments of a pseudotumor. PMID:26509089

  12. Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

    PubMed Central

    Lukovic, Dunja; Artero Castro, Ana; Delgado, Ana Belen Garcia; Bernal, María de los Angeles Martín; Luna Pelaez, Noelia; Díez Lloret, Andrea; Perez Espejo, Rocío; Kamenarova, Kunka; Fernández Sánchez, Laura; Cuenca, Nicolás; Cortón, Marta; Avila Fernandez, Almudena; Sorkio, Anni; Skottman, Heli; Ayuso, Carmen; Erceg, Slaven; Bhattacharya, Shomi S.

    2015-01-01

    Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches. PMID:26263531

  13. An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases

    PubMed Central

    Crosby-Nwaobi, Roxanne; Hykin, Philip; Peto, Tunde; Sivaprasad, Sobha

    2016-01-01

    Purpose The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Methods Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. Results A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. Conclusion Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases. PMID:27274188

  14. Network and atomistic simulations unveil the structural determinants of mutations linked to retinal diseases.

    PubMed

    Mariani, Simona; Dell'Orco, Daniele; Felline, Angelo; Raimondi, Francesco; Fanelli, Francesca

    2013-01-01

    A number of incurable retinal diseases causing vision impairments derive from alterations in visual phototransduction. Unraveling the structural determinants of even monogenic retinal diseases would require network-centered approaches combined with atomistic simulations. The transducin G38D mutant associated with the Nougaret Congenital Night Blindness (NCNB) was thoroughly investigated by both mathematical modeling of visual phototransduction and atomistic simulations on the major targets of the mutational effect. Mathematical modeling, in line with electrophysiological recordings, indicates reduction of phosphodiesterase 6 (PDE) recognition and activation as the main determinants of the pathological phenotype. Sub-microsecond molecular dynamics (MD) simulations coupled with Functional Mode Analysis improve the resolution of information, showing that such impairment is likely due to disruption of the PDEγ binding cavity in transducin. Protein Structure Network analyses additionally suggest that the observed slight reduction of theRGS9-catalyzed GTPase activity of transducin depends on perturbed communication between RGS9 and GTP binding site. These findings provide insights into the structural fundamentals of abnormal functioning of visual phototransduction caused by a missense mutation in one component of the signaling network. This combination of network-centered modeling with atomistic simulations represents a paradigm for future studies aimed at thoroughly deciphering the structural determinants of genetic retinal diseases. Analogous approaches are suitable to unveil the mechanism of information transfer in any signaling network either in physiological or pathological conditions. PMID:24009494

  15. Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

    PubMed

    Lee, J S; Lee, S M; Jeong, S W; Sung, Y G; Lee, J H; Kim, K W

    2016-07-01

    Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. PMID:27149303

  16. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. PMID:27589705

  17. Solid-state temporomandibular joint imaging: accuracy in detecting osseous changes of degenerative joint disease and determining condylar spatial relations.

    PubMed

    Scarfe, William C; Farman, Allan G; Silveira, Anibal; Fairbanks, Brandon W; Kelly, Paul J

    2003-10-01

    The purpose of this study was to evaluate the off-label use of an intraoral charge-coupled device (CCD) for extraoral transcranial radiography of the temporomandibular joint. Corrected linear tomograms and transcranial images made with conventional screen-film combinations and a CCD detector were compared with sectioned cadaver specimens. Radiation dosage, qualitative assessment of condylar degenerative features, and condylar position within the glenoid fossa of the 3 modalities were assessed and compared. The CCD method required special adjustments to achieve adequate quality, and it involved greater exposure than the other methods. This use of this intraoral system for extraoral imaging cannot now be recommended, but future refinements might make it more viable. PMID:14560277

  18. Cost Utility Analysis of the Cervical Artificial Disc vs Fusion for the Treatment of 2-Level Symptomatic Degenerative Disc Disease: 5-Year Follow-up

    PubMed Central

    Yang, Zhuo; Nunley, Pierce; Stone, Marcus B.; Lee, Darrin; Kim, Kee D.

    2016-01-01

    BACKGROUND: The cervical total disc replacement (cTDR) was developed to treat cervical degenerative disc disease while preserving motion. OBJECTIVE: Cost-effectiveness of this intervention was established by looking at 2-year follow-up, and this update reevaluates our analysis over 5 years. METHODS: Data were derived from a randomized trial of 330 patients. Data from the 12-Item Short Form Health Survey were transformed into utilities by using the SF-6D algorithm. Costs were calculated by extracting diagnosis-related group codes and then applying 2014 Medicare reimbursement rates. A Markov model evaluated quality-adjusted life years (QALYs) for both treatment groups. Univariate and multivariate sensitivity analyses were conducted to test the stability of the model. The model adopted both societal and health system perspectives and applied a 3% annual discount rate. RESULTS: The cTDR costs $1687 more than anterior cervical discectomy and fusion (ACDF) over 5 years. In contrast, cTDR had $34 377 less productivity loss compared with ACDF. There was a significant difference in the return-to-work rate (81.6% compared with 65.4% for cTDR and ACDF, respectively; P = .029). From a societal perspective, the incremental cost-effective ratio (ICER) for cTDR was −$165 103 per QALY. From a health system perspective, the ICER for cTDR was $8518 per QALY. In the sensitivity analysis, the ICER for cTDR remained below the US willingness-to-pay threshold of $50 000 per QALY in all scenarios (−$225 816 per QALY to $22 071 per QALY). CONCLUSION: This study is the first to report the comparative cost-effectiveness of cTDR vs ACDF for 2-level degenerative disc disease at 5 years. The authors conclude that, because of the negative ICER, cTDR is the dominant modality. ABBREVIATIONS: ACDF, anterior cervical discectomy and fusion AWP, average wholesale price CE, cost-effectiveness CEA, cost-effectiveness analysis CPT, Current Procedural Terminology cTDR, cervical total disc

  19. Global Transcriptome Analysis of the Tentacle of the Jellyfish Cyanea capillata Using Deep Sequencing and Expressed Sequence Tags: Insight into the Toxin- and Degenerative Disease-Related Transcripts

    PubMed Central

    Liu, Dan; Wang, Qianqian; Ruan, Zengliang; He, Qian; Zhang, Liming

    2015-01-01

    Background Jellyfish contain diverse toxins and other bioactive components. However, large-scale identification of novel toxins and bioactive components from jellyfish has been hampered by the low efficiency of traditional isolation and purification methods. Results We performed de novo transcriptome sequencing of the tentacle tissue of the jellyfish Cyanea capillata. A total of 51,304,108 reads were obtained and assembled into 50,536 unigenes. Of these, 21,357 unigenes had homologues in public databases, but the remaining unigenes had no significant matches due to the limited sequence information available and species-specific novel sequences. Functional annotation of the unigenes also revealed general gene expression profile characteristics in the tentacle of C. capillata. A primary goal of this study was to identify putative toxin transcripts. As expected, we screened many transcripts encoding proteins similar to several well-known toxin families including phospholipases, metalloproteases, serine proteases and serine protease inhibitors. In addition, some transcripts also resembled molecules with potential toxic activities, including cnidarian CfTX-like toxins with hemolytic activity, plancitoxin-1, venom toxin-like peptide-6, histamine-releasing factor, neprilysin, dipeptidyl peptidase 4, vascular endothelial growth factor A, angiotensin-converting enzyme-like and endothelin-converting enzyme 1-like proteins. Most of these molecules have not been previously reported in jellyfish. Interestingly, we also characterized a number of transcripts with similarities to proteins relevant to several degenerative diseases, including Huntington’s, Alzheimer’s and Parkinson’s diseases. This is the first description of degenerative disease-associated genes in jellyfish. Conclusion We obtained a well-categorized and annotated transcriptome of C. capillata tentacle that will be an important and valuable resource for further understanding of jellyfish at the molecular

  20. Optical Coherence Tomography Angiography of Miscellaneous Retinal Disease.

    PubMed

    Pierro, Luisa; Battaglia Parodi, Maurizio; Rabiolo, Alessandro; Introini, Ugo; Querques, Giuseppe; Bandello, Francesco

    2016-01-01

    In this chapter, we illustrate different clinical scenarios using swept-source optical coherence tomography angiography (OCTA, Triton, Topcon, Inc., Tokyo, Japan). The instrument is based on a long wavelength scanning light (1,050 nm) that can better penetrate the deeper ocular layers, such as the choroid and sclera. Our aim was to show how OCTA can be used to study the eye vascular network in a novel and innovative fashion. We have demonstrated that a specific disease can involve one or more layers; conversely, the same layer may be affected by different ocular pathologies. Moreover, we would like to stress that knowledge of disease pathophysiology is fundamental, and thus, we have focused our attention on the layer(s) most involved in each pathological condition. In some miscellaneous cases, the swept-source OCTA findings have corroborated with conventional imaging data (i.e. fundus photography, B-scan ultrasonography, fluorangiography and indocyanine green angiography), thus leading us to the proper diagnosis. PMID:27023316

  1. Changes in the foveal microstructure after intravitreal bevacizumab application in patients with retinal vascular disease

    PubMed Central

    Feucht, Nikolaus; Schönbach, Etienne Michael; Lanzl, Ines; Kotliar, Konstantin; Lohmann, Chris Patrick; Maier, Mathias

    2013-01-01

    Purpose To investigate changes in the area of the foveal avascular zone (FAZ) in patients with retinal vascular disease. Patients and methods This retrospective, consecutive study examined 53 eyes of 53 patients with macular edema due to branch retinal vein occlusion in 25 patients (47.2%) and nonproliferative diabetic retinopathy in 28 patients (52.8%). The macular edema was treated with an intravitreal injection of 0.05 mL equal to 1.25 mg bevacizumab. Before and 6–8 weeks after the injection, best corrected visual acuity, slit lamp biomicroscopy of the anterior segment and fundus, optical coherence tomography, and fluorescein angiography were conducted. The FAZ was manually circumscribed on early-phase angiography images and the area of the FAZ was measured. Results The preoperative overall mean FAZ area was 0.327 ± 0.126 mm2 (median 0.310 mm2). At the control consultation, the overall mean area was significantly larger (0.422 ± 0.259 mm2; median 0.380 mm2; P < 0.001). In the nonproliferative diabetic retinopathy subpopulation, the mean area was 0.361 ± 0.129 mm2 (median 0.330 mm2) before bevacizumab application and 0.434 mm2 at the follow-up visit (mean increase 0.071 mm2/19.7%). In the branch retinal vein occlusion group, the baseline FAZ area was 0.290 ± 0.115 mm2 and 0.407 ± 0.350 mm2 at follow-up (median 0.330 mm2; mean increase 0.117 mm2/40.3%). No cases of severe operation-associated complications were observed. Conclusion The results confirm the safety of intravitreal bevacizumab injection in patients with macular edema due to nonproliferative diabetic retinopathy and branch retinal vein occlusion. The enlargement of the FAZ could be equivalent to an increase in retinal ischemia. These results may be transient; a potential vascular risk, however, when applying antivascular endothelial growth factor therapy in eyes with preexistent vascular disease must be considered. PMID:23355773

  2. Retinal dysfunction, photoreceptor protein dysregulation and neuronal remodelling in the R6/1 mouse model of Huntington's disease.

    PubMed

    Batcha, Abrez Hussain; Greferath, Una; Jobling, Andrew I; Vessey, Kirstan A; Ward, Michelle M; Nithianantharajah, Jess; Hannan, Anthony J; Kalloniatis, Michael; Fletcher, Erica L

    2012-03-01

    Huntington's disease (HD) is a progressive neurological disease characterised by motor dysfunction, cognitive impairment and personality changes. Previous work in HD patients and animal models of the disease has also highlighted retinal involvement. This study characterised the changes in retinal structure and function early within the progression of disease using the R6/1 mouse model of HD. The retinal phenotype was observed to occur at the same time in the disease process as other neurological deficits such as motor dysfunction (by 13 weeks of age). There was a specific functional deficit in cone response to the electroretinogram and using immunocytochemical techniques, this dysfunction was found to be likely due to a progressive and complete loss of cone opsin and transducin protein expression by 20 weeks of age. In addition, there was an increase in Müller cell gliosis and the presence of ectopic rod photoreceptor terminals. This retinal remodelling is also observed in downstream neurons, namely the rod and cone bipolar cells. While R6/1 mice exhibit significant retinal pathology simultaneously with other more classical HD alterations, this doesn't lead to extensive cell loss. These findings suggest that in HD, cone photoreceptors are initially targeted, possibly via dysregulation of protein expression or trafficking and that this process is subsequently accompanied by increased retinal stress and neuronal remodelling also involving the rod pathway. As retinal structure and connectivity are well characterised, the retina may provide a useful model tissue in which to characterise the mechanisms important in the development of neuronal pathology in HD. PMID:22198376

  3. Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina Cultures Derived From Human Reporter Pluripotent Stem Cell Lines.

    PubMed

    Kaewkhaw, Rossukon; Swaroop, Manju; Homma, Kohei; Nakamura, Jutaro; Brooks, Matthew; Kaya, Koray Dogan; Chaitankar, Vijender; Michael, Sam; Tawa, Gregory; Zou, Jizhong; Rao, Mahendra; Zheng, Wei; Cogliati, Tiziana; Swaroop, Anand

    2016-04-01

    We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration. PMID:27116668

  4. Combined transforaminal lumbar interbody fusion with posterolateral instrumented fusion for degenerative disc disease can be a safe and effective treatment for lower back pain

    PubMed Central

    Deukmedjian, Ara J; Cianciabella, Augusto J; Cutright, Jason; Deukmedjian, Arias

    2015-01-01

    Background: Lumbar fusion is a proven treatment for chronic lower back pain (LBP) in the setting of symptomatic spondylolisthesis and degenerative scoliosis; however, fusion is controversial when the primary diagnosis is degenerative disc disease (DDD). Our objective was to evaluate the safety and effectiveness of lumbar fusion in the treatment of LBP due to DDD. Materials and Methods: Two-hundred and five consecutive patients with single or multi-level DDD underwent lumbar decompression and instrumented fusion for the treatment of chronic LBP between the years of 2008 and 2011. The primary outcome measures in this study were back and leg pain visual analogue scale (VAS), patient reported % resolution of preoperative back pain and leg pain, reoperation rate, perioperative complications, blood loss and hospital length of stay (LOS). Results: The average resolution of preoperative back pain per patient was 84% (n = 205) while the average resolution of preoperative leg pain was 90% (n = 190) while a mean follow-up period of 528 days (1.5 years). Average VAS for combined back and leg pain significantly improved from a preoperative value of 9.0 to a postoperative value of 1.1 (P ≤ 0.0001), a change of 7.9 points for the cohort. The average number of lumbar disc levels fused per patient was 2.3 (range 1-4). Median postoperative LOS in the hospital was 1.2 days. Average blood loss was 108 ml perfused level. Complications occurred in 5% of patients (n = 11) and the rate of reoperation for symptomatic adjacent segment disease was 2% (n = 4). Complications included reoperation at index level for symptomatic pseudoarthrosis with hardware failure (n = 3); surgical site infection (n = 7); repair of cerebrospinal fluid leak (n = 1), and one patient death at home 3 days after discharge. Conclusion: Lumbar fusion for symptomatic DDD can be a safe and effective treatment for medically refractory LBP with or without leg pain. PMID:26692696

  5. Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease.

    PubMed

    Gautschi, Oliver P; Corniola, Marco V; Smoll, Nicolas R; Joswig, Holger; Schaller, Karl; Hildebrandt, Gerhard; Stienen, Martin N

    2016-05-01

    Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland-Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease. PMID:26761383

  6. Progesterone receptor signalling in retinal photoreceptor neuroprotection.

    PubMed

    Jackson, Alice C Wyse; Roche, Sarah L; Byrne, Ashleigh M; Ruiz-Lopez, Ana M; Cotter, Thomas G

    2016-01-01

    'Norgestrel', a synthetic form of the female hormone progesterone has been identified as potential drug candidate for the treatment of the degenerative eye disease retinitis pigmentosa. However, to date, no work has looked at the compound's specific cellular target. Therefore, this study aimed to identify the receptor target of Norgestrel and begin to examine its potential mechanism of action in the retina. In this work, we identify and characterize the expression of progesterone receptors present in the C57 wild type and rd10 mouse model of retinitis pigmentosa. Classical progesterone receptors A and B (PR A/B), progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) and membrane progesterone receptors α, β and γ were found to be expressed. All receptors excluding PR A/B were also found in the 661W photoreceptor cell line. PGRMC1 is a key regulator of apoptosis and its expression is up-regulated in the degenerating rd10 mouse retina. Activated by Norgestrel through nuclear trafficking, siRNA knock down of PGRMC1 abrogated the protective properties of Norgestrel on damaged photoreceptors. Furthermore, specific inhibition of PGRMC1 by AG205 blocked Norgestrel-induced protection in stressed retinal explants. Therefore, we conclude that PGRMC1 is crucial to the neuroprotective effects of Norgestrel on stressed photoreceptors. The synthetic progestin 'Norgestrel' has been identified as a potential therapeutic for the treatment of Retinitis Pigmentosa, a degenerative eye disease. However, the mechanism behind this neuroprotection is currently unknown. In this work, we identify 'Progesterone Receptor Membrane Component 1' as the major progesterone receptor eliciting the protective effects of Norgestrel, both in vitro and ex vivo. This furthers our understanding of Norgestrel's molecular mechanism, which we hope will help bring Norgestrel one step closer to the clinic. PMID:26447367

  7. Evaluation of the Retinal Vasculature in Hypertension and Chronic Kidney Disease in an Elderly Population of Irish Nuns

    PubMed Central

    McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C.; Maxwell, Alexander P.; McKay, Gareth J.

    2015-01-01

    Background Chronic kidney disease (CKD) and hypertension are global public health problems associated with considerable morbidity, premature mortality and attendant healthcare costs. Previous studies have highlighted that non-invasive examination of the retinal microcirculation can detect microvascular pathology that is associated with systemic disorders of the circulatory system such as hypertension. We examined the associations between retinal vessel caliber (RVC) and fractal dimension (DF), with both hypertension and CKD in elderly Irish nuns. Methods Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study (INES) were assessed from digital photographs with a standardized protocol using computer-assisted software. Multivariate regression analyses were used to assess associations with hypertension and CKD, with adjustment for age, body mass index (BMI), refraction, fellow eye RVC, smoking, alcohol consumption, ischemic heart disease (IHD), cerebrovascular accident (CVA), diabetes and medication use. Results In total, 1122 (91%) participants (mean age: 76.3 [range: 56–100] years) had gradable retinal images of sufficient quality for blood vessel assessment. Hypertension was significantly associated with a narrower central retinal arteriolar equivalent (CRAE) in a fully adjusted analysis (P = 0.002; effect size = -2.16 μm; 95% confidence intervals [CI]: -3.51, -0.81 μm). No significant associations between other retinal vascular parameters and hypertension or between any retinal vascular parameters and CKD were found. Conclusions Individuals with hypertension have significantly narrower retinal arterioles which may afford an earlier opportunity for tailored prevention and treatment options to optimize the structure and function of the microvasculature, providing additional clinical utility. No significant associations between retinal vascular parameters and CKD were detected. PMID:26327531

  8. Mutations in human IFT140 cause non-syndromic retinal degeneration.

    PubMed

    Xu, Mingchu; Yang, Lizhu; Wang, Feng; Li, Huajin; Wang, Xia; Wang, Weichen; Ge, Zhongqi; Wang, Keqing; Zhao, Li; Li, Hui; Li, Yumei; Sui, Ruifang; Chen, Rui

    2015-10-01

    Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are two genetically heterogeneous retinal degenerative disorders. Despite the identification of a number of genes involved in LCA and RP, the genetic etiology remains unknown in many patients. In this study, we aimed to identify novel disease-causing genes of LCA and RP. Retinal capture sequencing was initially performed to screen mutations in known disease-causing genes in different cohorts of LCA and RP patients. For patients with negative results, we performed whole exome sequencing and applied a series of variant filtering strategies. Sanger sequencing was done to validate candidate causative IFT140 variants. Exome sequencing data analysis led to the identification of IFT140 variants in multiple unrelated non-syndromic LCA and RP cases. All the variants are extremely rare and predicted to be damaging. All the variants passed Sanger validation and segregation tests provided that the family members' DNA was available. The results expand the phenotype spectrum of IFT140 mutations to non-syndromic retinal degeneration, thus extending our understanding of intraflagellar transport and primary cilia biology in the retina. This work also improves the molecular diagnosis of retinal degenerative disease. PMID:26216056

  9. Progress of mesenchymal stem cell therapy for neural and retinal diseases

    PubMed Central

    Ng, Tsz Kin; Fortino, Veronica R; Pelaez, Daniel; Cheung, Herman S

    2014-01-01

    Complex circuitry and limited regenerative power make central nervous system (CNS) disorders the most challenging and difficult for functional repair. With elusive disease mechanisms, traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases. However, the number of neurons still diminishes in many patients. Recently, stem cell therapy has been proposed as a viable option. Mesenchymal stem cells (MSCs), a widely-studied human adult stem cell population, have been discovered for more than 20 years. MSCs have been found all over the body and can be conveniently obtained from different accessible tissues: bone marrow, blood, and adipose and dental tissue. MSCs have high proliferative and differentiation abilities, providing an inexhaustible source of neurons and glia for cell replacement therapy. Moreover, MSCs also show neuroprotective effects without any genetic modification or reprogramming. In addition, the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation. These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders. Here, we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases. This review article will focus on multiple sclerosis, spinal cord injury, autism, glaucoma, retinitis pigmentosa and age-related macular degeneration. PMID:24772238

  10. Toward comprehensive detection of sight threatening retinal disease using a multiscale AM-FM methodology

    NASA Astrophysics Data System (ADS)

    Agurto, C.; Barriga, S.; Murray, V.; Murillo, S.; Zamora, G.; Bauman, W.; Pattichis, M.; Soliz, P.

    2011-03-01

    In the United States and most of the western world, the leading causes of vision impairment and blindness are age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. In the last decade, research in automatic detection of retinal lesions associated with eye diseases has produced several automatic systems for detection and screening of AMD, DR, and glaucoma. However. advanced, sight-threatening stages of DR and AMD can present with lesions not commonly addressed by current approaches to automatic screening. In this paper we present an automatic eye screening system based on multiscale Amplitude Modulation-Frequency Modulation (AM-FM) decompositions that addresses not only the early stages, but also advanced stages of retinal and optic nerve disease. Ten different experiments were performed in which abnormal features such as neovascularization, drusen, exudates, pigmentation abnormalities, geographic atrophy (GA), and glaucoma were classified. The algorithm achieved an accuracy detection range of [0.77 to 0.98] area under the ROC curve for a set of 810 images. When set to a specificity value of 0.60, the sensitivity of the algorithm to the detection of abnormal features ranged between 0.88 and 1.00. Our system demonstrates that, given an appropriate training set, it is possible to use a unique algorithm to detect a broad range of eye diseases.

  11. The burden of disease of retinal vein occlusion: review of the literature.

    PubMed

    Laouri, M; Chen, E; Looman, M; Gallagher, M

    2011-08-01

    Retinal vein occlusion (RVO) is the second most common cause of vision loss due to retinal vascular disease. A literature review was undertaken to understand the epidemiology, clinical consequence, current practice patterns, and cost of RVO. Pertinent articles were identified by computerized searches of the English language literature in MEDLINE supplemented with electronic and manual searches of society/association proceedings and bibliographies of electronically identified sources. Population-based studies report a prevalence rate of 0.5-2.0% for branch RVO and 0.1-0.2% for central RVO. The 15-year incidence rate is estimated to be 1.8% for branch RVO and 0.2% for central RVO. Patients with RVO report lower vision-related quality of life than those without ocular disease. Available treatment options are limited. Until recently there was no treatment for central RVO. Laser photocoagulation is only recommended for branch RVO in patients who have not experienced severe vision loss. Emerging evidence on the effectiveness of intravitreal anti-vascular endothelial growth factor therapy and dexamethasone intravitreal implant is promising. Information on the treatment patterns and cost of RVO is extremely limited with one retrospective analysis of secondary insurance payment data identified and limited to the United States population only. A better understanding of the economic and societal impact of RVO will help decision makers evaluate emerging medical interventions for this sight-threatening disease. PMID:21546916

  12. Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies

    PubMed Central

    Tiwari, Amit; Bahr, Angela; Bähr, Luzy; Fleischhauer, Johannes; Zinkernagel, Martin S.; Winkler, Niklas; Barthelmes, Daniel; Berger, Lieselotte; Gerth-Kahlert, Christina; Neidhardt, John; Berger, Wolfgang

    2016-01-01

    Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease-causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population. PMID:27353947

  13. Halting progressive neurodegeneration in advanced retinitis pigmentosa

    PubMed Central

    Koch, Susanne F.; Tsai, Yi-Ting; Duong, Jimmy K.; Wu, Wen-Hsuan; Hsu, Chun-Wei; Wu, Wei-Pu; Bonet-Ponce, Luis; Lin, Chyuan-Sheng; Tsang, Stephen H.

    2015-01-01

    Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed by loss of cones. While retinal gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset in patients. The lack of sustained benefit could be due to insufficient transduction efficiency of viral vectors (“too little”) and/or because the disease is too advanced (“too late”) at the time therapy is initiated. Here, we tested the latter hypothesis and developed a mouse RP model that permits restoration of the mutant gene in all diseased photoreceptor cells, thereby ensuring sufficient transduction efficiency. We then treated mice at early, mid, or late disease stages. At all 3 time points, degeneration was halted and function was rescued for at least 1 year. Not only do our results demonstrate that gene therapy effectively preserves function after the onset of degeneration, our study also demonstrates that there is a broad therapeutic time window. Moreover, these results suggest that RP patients are treatable, despite most being diagnosed after substantial photoreceptor loss, and that gene therapy research must focus on improving transduction efficiency to maximize clinical impact. PMID:26301813

  14. [Animal models of human retinal and optic nerve diseases analysed using electroretinography].

    PubMed

    Kondo, Mineo

    2010-03-01

    Investigations of animal models with diseases found in humans are important to the understanding of their pathophysiology and for developing new treatments. Both naturally occurring and genetically-manipulated animal models of human retinal and optic nerve diseases have been studied in this manner. Electroretinography (ERG) is valuable for the evaluation of the visual function of animal models, because a layer-by-layer assessment of the retina can be done objectively. We used ERGs to analyze the visual functions of animal models of human retinal and and optic nerve diseases. To investigate the contribution of the cone ON- and OFF-pathways to the mouse photopic ERGs, we studied the properties of the photopic ERGs of metabotropic glutamate receptor subtype 6-deficient mice. The results of the ERG and the effect of an intravitreous injection of cis-2,3 piperidine dicarboxylic acid (PDA) in these mice suggest that the contribution of the post-synaptic ON-pathway to the photopic ERG of mice is larger than that of the OFF-pathway. The ERGs of pikachurin-deficient mice had normal a-waves with severely delayed b-waves, indicating that the signal transmission from the photoreceptors to the bipolar cells was impaired in these mutant mice. We also generated a rabbit model of retinitis pigmentosa (RP), the rhodopsin P347L transgenic (Tg) rabbit, by using bacterial artificial chromosome (BAC) transgenesis. These rabbits showed a rod-dominant, progressive retinal degeneration with marked regional variations in the loss of photoreceptors. All ERG components of the Tg rabbits decreased progressively with the a-waves more affected than the b-waves, and with the oscillatory potentials (OPs) the best preserved. Interestingly, the OP amplitudes of young Tg rabbits were significantly larger than those of wild-type rabbits. Pharmacological experiments showed that the significantly larger OPs in young Tg rabbits resulted from secondary alterations in the inner retinal function. This type

  15. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment

  16. Retinitis pigmentosa: impact of different Pde6a point mutations on the disease phenotype.

    PubMed

    Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Jiao, Kangwei; Buena-Atienza, Elena; Sahaboglu, Ayse; Trifunović, Dragana; Balendran, Sukirthini; Koepfli, Tanja; Mühlfriedel, Regine; Schön, Christian; Biel, Martin; Heckmann, Angelique; Beck, Susanne C; Michalakis, Stylianos; Wissinger, Bernd; Seeliger, Mathias W; Paquet-Durand, François

    2015-10-01

    Mutations in the PDE6A gene can cause rod photoreceptors degeneration and the blinding disease retinitis pigmentosa (RP). While a number of pathogenic PDE6A mutations have been described, little is known about their impact on compound heterozygous situations and potential interactions of different disease-causing alleles. Here, we used a novel mouse model for the Pde6a R562W mutation in combination with an existing line carrying the V685M mutation to generate compound heterozygous Pde6a V685M/R562W animals, exactly homologous to a case of human RP. We compared the progression of photoreceptor degeneration in these compound heterozygous mice with the homozygous V685M and R562W mutants, and additionally with the D670G line that is known for a relatively mild phenotype. We investigated PDE6A expression, cyclic guanosine mono-phosphate accumulation, calpain and caspase activity, in vivo retinal function and morphology, as well as photoreceptor cell death and survival. This analysis confirms the severity of different Pde6a mutations and indicates that compound heterozygous mutants behave like intermediates of the respective homozygous situations. Specifically, the severity of the four different Pde6a situations may be categorized by the pace of photoreceptor degeneration: V685M (fastest) > V685M/R562W > R562W > D670G (slowest). While calpain activity was strongly increased in all four mutants, caspase activity was not. This points to the execution of non-apoptotic cell death and may lead to the identification of new targets for therapeutic interventions. For individual RP patients, our study may help to predict time-courses for Pde6a-related retinal degeneration and thereby facilitate the definition of a window-of-opportunity for clinical interventions. PMID:26188004

  17. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates

    PubMed Central

    Boloc, Daniel; Castillo-Lara, Sergio; Marfany, Gemma; Gonzàlez-Duarte, Roser; Abril, Josep F.

    2015-01-01

    Background Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies. Methodology We have built an RP-specific network (RPGeNet) by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space. Conclusions In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates. PMID:26267445

  18. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

  19. Branch retinal vein occlusion.

    PubMed

    Hamid, Sadaf; Mirza, Sajid Ali; Shokh, Ishrat

    2008-01-01

    Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are the two basic types of vein occlusion. Branch retinal vein occlusion is three times more common than central retinal vein occlusion and- second only to diabetic retinopathy as the most common retinal vascular cause of visual loss. The origin of branch retinal vein occlusion undoubtedly includes both systemic factors such as hypertension and local anatomic factors such as arteriovenous crossings. Branch retinal vein occlusion causes a painless decrease in vision, resulting in misty or distorted vision. Current treatment options don't address the underlying aetiology of branch retinal vein occlusion. Instead they focus on treating sequelae of the occluded venous branch, such as macular oedema, vitreous haemorrhage and traction retinal detachment from neovascularization. Evidences suggest that the pathogenesis of various types of retinal vein occlusion, like many other ocular vascular occlusive disorders, is a multifactorial process and there is no single magic bullet that causes retinal vein occlusion. A comprehensive management of patients with retinal vascular occlusions is necessary to correct associated diseases or predisposing abnormalities that could lead to local recurrences or systemic event. Along with a review of the literature, a practical approach for the management of retinal vascular occlusions is required, which requires collaboration between the ophthalmologist and other physicians: general practitioner, cardiologist, internist etc. as appropriate according to each case. PMID:19385476

  20. Light-induced retinal degeneration is prevented by zinc, a component in the age-related eye disease study formulation.

    PubMed

    Organisciak, Daniel; Wong, Paul; Rapp, Christine; Darrow, Ruth; Ziesel, Alison; Rangarajan, Rekha; Lang, John

    2012-01-01

    Mineral supplements are often included in multivitamin preparations because of their beneficial effects on metabolism. In this study, we used an animal model of light-induced retinal degeneration to test for photoreceptor cell protection by the essential trace element zinc. Rats were treated with various doses of zinc oxide and then exposed to intense visible light for as long as 8 h. Zinc treatment effectively prevented retinal light damage as determined by rhodopsin and retinal DNA recovery, histology and electrophoretic analysis of DNA damage and oxidized retinal proteins. Zinc oxide was particularly effective when given before light exposure and at doses two- to four-fold higher than recommended by the age-related eye disease study group. Treated rats exhibited higher serum and retinal pigment epithelial zinc levels and an altered retinal gene expression profile. Using an Ingenuity database, 512 genes with known functional annotations were found to be responsive to zinc supplementation, with 45% of these falling into a network related to cellular growth, proliferation, cell cycle and death. Although these data suggest an integrated and extensive regulatory response, zinc induced changes in gene expression also appear to enhance antioxidative capacity in retina and reduce oxidative damage arising from intense light exposure. PMID:22385127

  1. Zebrafish (Danio rerio) embryo as a platform for the identification of novel angiogenesis inhibitors of retinal vascular diseases.

    PubMed

    Rezzola, Sara; Paganini, Giuseppe; Semeraro, Francesco; Presta, Marco; Tobia, Chiara

    2016-07-01

    Pathological angiogenesis of the retina is a main cause of blindness. Therapeutic approaches targeting vascular endothelial growth factor, a main angiogenesis inducer in retinal vascular diseases, show significant limitations. Thus, experimental models of retinal neovascularization remain crucial for investigating novel anti-angiogenic strategies and bringing them to patients. Recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryo may represent a novel target for the identification of angiogenesis inhibitors. This review highlights the use of zebrafish embryo as an innovative model system for the screening of anti-angiogenic molecules to be employed for the treatment of angiogenesis-dependent eye diseases. PMID:27085972

  2. Retinal Diseases

    MedlinePlus

    ... Campaign to End Blindness Other Ways to Fight Blindness Corporate Support Volunteer Take Action You are here ... In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even ...

  3. Topical difluprednate for treatment of serous retinal detachment and panuveitis associated with Vogt-Koyanagi-Harada disease

    PubMed Central

    Lu, Stacey; Taban, Mehran

    2016-01-01

    Summary Patients with bilateral serous retinal detachments and panuveitis related to Vogt-Koyanagi-Harada disease are commonly managed with oral corticosteroids, immunosuppressive agents, and/or intravitreal injections. We present the case of a 56-year-old Hispanic man with Harada disease whose bilateral serous retinal detachments and panuveitis were treated with topical corticosteroid difluprednate alone. Functional and anatomical recoveries were assessed by fluorescein angiograms and optical coherence tomography studies over a period of 9 months. The patient’s serous retinal detachments resolved, and his vision and panuveitis improved dramatically over a period of 2 weeks, after which he was placed on a drop taper and maintenance therapy for the remainder of the 9 months. PMID:27582676

  4. Angio-OCT as a noninvasive tool for three-dimensional vascular network visualization in retinal diseases

    NASA Astrophysics Data System (ADS)

    Bukowska, D.; Ruminski, D.; Sikorski, B. L.; Gorczynska, I.; Borycki, D.; Szkulmowski, M.; Wojtkowski, M.

    2013-06-01

    In this paper we demonstrate applicability of intensity-based optical coherence tomography technique for noninvasive visualization of 3D retinal microcapillary network. The study was performed with ultra high resolution and high speed (180,000 Ascans/sec) spectral optical coherence tomography (SOCT). New scanning protocols and data processing algorithms have been introduced to visualize microcapillary network. Moreover, results obtained in the eyes of healthy volunteers and patients with eye diseases were compared with fluorescein angiography. Presented report shows that SOCT is well suited for visualization of 3D retinal capillary network in the healthy and pathologic eyes as well. Obtained results demonstrate high correspondence with fluorescein angiography, without using any contrast agents. Our data suggest that intensity-based SOCT has potential in the early diagnosis of the retinal vascular diseases.

  5. Topical difluprednate for treatment of serous retinal detachment and panuveitis associated with Vogt-Koyanagi-Harada disease.

    PubMed

    Lu, Stacey; Taban, Mehran

    2016-01-01

    Patients with bilateral serous retinal detachments and panuveitis related to Vogt-Koyanagi-Harada disease are commonly managed with oral corticosteroids, immunosuppressive agents, and/or intravitreal injections. We present the case of a 56-year-old Hispanic man with Harada disease whose bilateral serous retinal detachments and panuveitis were treated with topical corticosteroid difluprednate alone. Functional and anatomical recoveries were assessed by fluorescein angiograms and optical coherence tomography studies over a period of 9 months. The patient's serous retinal detachments resolved, and his vision and panuveitis improved dramatically over a period of 2 weeks, after which he was placed on a drop taper and maintenance therapy for the remainder of the 9 months. PMID:27582676

  6. Comparative Analysis of Interbody Cages Versus Tricortical Graft with Anterior Plate Fixation for Anterior Cervical Discectomy and Fusion in Degenerative Cervical Disc Disease

    PubMed Central

    Singh, Pritish; Shekhawat, Vishal

    2016-01-01

    Introduction Multiple techniques and modalities of fixation are used in Anterior Cervical Discectomy and interbody Fusion (ACDF), each with some merit and demerit against others. Such pool of techniques reflects lack of a consensus method conducive to uniformly good results. Aim A prospective study was done to analyse safety and efficacy of tricortical autograft and anterior cervical plate (Group A) with cylindrical titanium cage filled with cancellous bone (Group B) in procedure of ACDF for single level degenerative cervical disc disease. Materials and Methods Twenty patients with degenerative cervical disc disease were included in study for ACDF. After a computer generated randomisation, ten patients (10 segments) were operated with anterior locking plating and tricortical iliac crest graft (Group A, Tricortical graft group), while ten patients(10 segments) were operated with standalone cylindrical titanium cages filled with cancellous bone harvested using minimally invasive methods (Group B, Cage group) from April 2012 to May 2015. Odoms’s criteria, visual pain analogue score and sequential plain radiographs were obtained to assess for clinic-radiological outcome. Results According to Odom’s system of functional assessment, 9 patients from each group (90%) experienced good to excellent functional recovery and 9 of 10 (90%) patients of each groups were satisfied with outcome. In both groups, relief in neck pain or arm pain was similar without any statistical difference as assessed by visual analogue score. Fusion was present in 10 of 10 (100%) patients in tricortical graft group and 10 of 10 (100%) in cage group at the end of 6 months. There was no implant related complications in cage group. Transient postoperative dysphagia was recorded in 3 patients (2 in Group A and 1 in group B), which resolved within 3 days. In tricortical graft group, graft collapse and partial extrusion was detected in one patient, which did not correspond with good results obtained

  7. [Musculoskeletal pathology in occupational risks and common degenerative disease: reflections on the intensity and duration of the risk].

    PubMed

    Bergamini, Roberta; Astengo, Rossana

    2014-01-01

    Nowadays, in Italy the reports of mnusculoskeletal diseases increase as confirmed in the last INAIL (national insurance for occupational diseases and injuries) annual report. The Emilia-Ronmagna is one of the region with the highest number of reports: 15.9% of the total in 2012. The decree no. 81/08 has partially simplified the medico-legal activities related to musculoskeletal diseases; however, the medico-legal physicians have still to deal with some issues such as risk assessment quality, economic crisis, and specific work environments (e.g. agriculture and many handicraft activities). Tire risk factors of musculoskeletal diseases and their assessments are quite well studied. The latency period of these diseases needs to be investigated, since it could be a relevant aspect for legal medical judgment, insurance protection and prevention. Based on literature data and INAIL experience, authors propose some considerations useful for a scientific debate. PMID:25558730

  8. Retinal function and morphology are altered in cattle infected with the prion disease transmissible mink encephalopathy.

    PubMed

    Smith, J D; Greenlee, J J; Hamir, A N; Richt, J A; Greenlee, M H West

    2009-09-01

    Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein-contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy ("mad cow disease") to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy-inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy-infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Müller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of

  9. Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Retinal Diseases.

    PubMed

    Rodrigues, Eduardo Büchele; Farah, Michel Eid; Bottós, Juliana Mantovani; Bom Aggio, Fabio

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of drugs in medicine and ophthalmology. Several NSAIDs have been commercially available for many years: diclofenac, flurbiprofen, indomethacin, ketorolac and suprofen. The purpose of this chapter is to review the clinical use of earlier and newer pharmacologic agents of the NSAID class. NSAIDs may have a modulating effect on ocular inflammation and pain through the prevention of prostaglandin synthesis via cyclooxygenase inhibition. Newer-generation NSAIDs have emerged in recent years for the treatment of ocular pain and inflammation. Nepafenac ophthalmic suspension 0.1% is a new topical NSAID prodrug that has been approved by the Food and Drug Administration for the treatment of pain and inflammation after cataract surgery. Preliminary data suggest nepafenac may also provide unique efficacy in the posterior segment, since its corneal permeability characteristics are superior to those of other NSAIDs. Nevanac, diclofenac, ketorolac and bromfenac are some notable NSAID candidates which should be investigated intravitreally or topically for retinal pharmacotherapy. In addition, for intraocular surgery, NSAIDs can help to prevent intraoperative miosis, reduce ocular pain, decrease postoperative inflammation and prevent cystoid macular edema. Retinal, choroidal and vitreous diseases may be the target of future nepafenac studies, either as monotherapy or as combination treatments. PMID:26502088

  10. End Stage Renal Disease as a Potential Risk Factor for Retinal Vein Occlusion.

    PubMed

    Chen, San-Ni; Yang, Te-Cheng; Lin, Jian-Teng; Lian, Ie-Bin

    2015-11-01

    End stage renal disease (ESRD) has been reported to be an important risk factor for systemic vascular disease. Retinal vein occlusion (RVO) is closely related with cardiovascular diseases; however, its association with ESRD had not been reported. The aim of the study was to investigate whether ESRD is a risk factor for RVO, including central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). This population-based study is based on the longitudinal data from Taiwan National Health Insurance Research Database. The study cohort comprised 5344 patients with diagnosis of ESRD on hemodialysis or peritoneal dialysis during the period from January 1996 to December 2011. For each ESRD patient, we selected 20 non-ESRD patients matched on age and sex. Each ESRD patient and his/her controls were followed from the initiation of renal dialysis until either the diagnosis of RVO or censorship. Kaplan-Meier method was used to compare the hazard of RVO between cohorts. Stratified Cox proportional hazard models were applied to estimate the hazard ratio (HR) adjusted by the comorbidities of RVO including diabetes mellitus (DM), hypertension, hypercholesteremia, and hypertriglyceridemia. After stratifying by DM status, the statistics were applied again to examine the associations among the DM cohort and non-DM cohort.The 16-year RVO cumulative incidence for ESRD cohort was 2-fold to the non-ESRD (1.01% vs 0.46%). After matching with age, sex, hypertension, and hypercholesteremia, the adjusted HR was 1.46 (95% confidence interval = 1.07-2.01, P value = 0.018). By further excluding patients with DM, the adjusted HR escalated to 2.43 (95% confidence interval = 1.54-3.83, P < 0.001). In contrast, there was no significant risk of ESRD on RVO in the DM patients (HR = 1.03). We conclude that among the non-DM patients, ESRD cases had significantly higher RVO rate than the non-ESRD, which indicates that ESRD maybe a potential risk factor for the development of RVO in

  11. The association of central retinal artery occlusion and extracranial carotid artery disease.

    PubMed Central

    Douglas, D J; Schuler, J J; Buchbinder, D; Dillon, B C; Flanigan, D P

    1988-01-01

    To determine the incidence of associated carotid artery disease and the effect of carotid endarterectomy on subsequent neurologic sequelae, a retrospective study of 66 patients with central retinal artery occlusion (CRAO) was undertaken. Ipsilateral extracranial carotid artery disease was present in 23 of 33 patients (70%) who had carotid arteriography. Sixteen patients had carotid endarterectomy following their CRAO (Group I) and 50 did not (Group II). Seven of the 40 patients available for follow-up in Group II had a subsequent stroke (mean follow-up: 54 months). Of the seven Group II patients shown to have associated carotid disease (Group IIs), three (43%) had a subsequent stroke during follow-up (mean: 28.3 months) compared to zero in Group I (p = 0.033; mean follow-up: 18.7 months). Because of the strong association between CRAO and ipsilateral carotid artery disease and because of the significantly higher incidence of subsequent ipsilateral stroke in CRAO patients with carotid disease who did not undergo endarterectomy, thorough evaluation of the carotid arteries followed by carotid endarterectomy, if indicated, is warranted in CRAO patients who have no other obvious etiology for the occlusion. PMID:3389947

  12. Microtubule-associated protein tau in bovine retinal photoreceptor rod outer segments: comparison with brain tau.

    PubMed

    Yamazaki, Akio; Nishizawa, Yuji; Matsuura, Isao; Hayashi, Fumio; Usukura, Jiro; Bondarenko, Vladimir A

    2013-10-01

    Recent studies have suggested a possible involvement of abnormal tau in some retinal degenerative diseases. The common view in these studies is that these retinal diseases share the mechanism of tau-mediated degenerative diseases in brain and that information about these brain diseases may be directly applied to explain these retinal diseases. Here we collectively examine this view by revealing three basic characteristics of tau in the rod outer segment (ROS) of bovine retinal photoreceptors, i.e., its isoforms, its phosphorylation mode and its interaction with microtubules, and by comparing them with those of brain tau. We find that ROS contains at least four isoforms: three are identical to those in brain and one is unique in ROS. All ROS isoforms, like brain isoforms, are modified with multiple phosphate molecules; however, ROS isoforms show their own specific phosphorylation pattern, and these phosphorylation patterns appear not to be identical to those of brain tau. Interestingly, some ROS isoforms, under the normal conditions, are phosphorylated at the sites identical to those in Alzheimer's patient isoforms. Surprisingly, a large portion of ROS isoforms tightly associates with a membranous component(s) other than microtubules, and this association is independent of their phosphorylation states. These observations strongly suggest that tau plays various roles in ROS and that some of these functions may not be comparable to those of brain tau. We believe that knowledge about tau in the entire retinal network and/or its individual cells are also essential for elucidation of tau-mediated retinal diseases, if any. PMID:23712071

  13. Guiding the morphogenesis of dissociated newborn mouse retinal cells and hES cell-derived retinal cells by soft lithography-patterned microchannel PLGA scaffolds

    PubMed Central

    McUsic, Andrew C.; Lamba, Deepak A.; Reh, Thomas A.

    2011-01-01

    Embryonic stem (ES) cell-derived photoreceptors are a promising cell source for enhanced in vitro models of retinal degenerative diseases, but the more differentiated characteristics of retinal cells do not typically develop in dissociated cell cultures. Therefore, we have reconstructed organized retinal tissue by seeding dissociated cells into an array of aligned units that more faithfully mimics the retina. We solvent-processed poly(lactic-co-glycolic acid) (PLGA) into a microchannel scaffold format to achieve this geometric constraint. We compared the effect of PLGA concentration on channel morphology and, along with other culture conditions, on the infiltration of dissociated newborn mouse retinal cells into the channels. Culturing scaffolds at the gas-liquid interface with low serum media increased infiltrated rod photoreceptor viability 18-fold over submerged, high serum cultures when evaluated after seven days. Rod photoreceptors and Müller glia aligned processes parallel to the microchannel walls. Otx2+ and Pax6+ subpopulations recapitulated lamination behavior. Further, we constructed scaffold/retinal pigment epithelium (RPE) co-cultures and observed rods extending rhodopsin-positive processes toward RPE cells, mimicking normal rod polarization and morphology. Finally, human embryonic stem cell-derived photoreceptors exhibited infiltration and morphological characteristics similar to mouse retinal cells inside the scaffolds. These findings constitute an important advance in generating tissue-level retinal models from dissociated cells for use as drug screening platforms and in regenerative medicine. PMID:22115999

  14. Differential Diagnosis of Retinal Vasculitis

    PubMed Central

    Abu El-Asrar, Ahmed M.; Herbort, Carl P.; Tabbara, Khalid F.

    2009-01-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings. PMID:20404987

  15. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    PubMed

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  16. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    PubMed Central

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  17. RNA-Seq: Improving Our Understanding of Retinal Biology and Disease.

    PubMed

    Farkas, Michael H; Au, Elizabeth D; Sousa, Maria E; Pierce, Eric A

    2015-01-01

    Over the past several years, rapid technological advances have allowed for a dramatic increase in our knowledge and understanding of the transcriptional landscape, because of the ability to study gene expression in greater depth and with more detail than previously possible. To this end, RNA-Seq has quickly become one of the most widely used methods for studying transcriptomes of tissues and individual cells. Unlike previously favored analysis methods, RNA-Seq is extremely high-throughput, and is not dependent on an annotated transcriptome, laying the foundation for novel genetic discovery. Additionally, RNA-Seq derived transcriptomes provide a basis for widening the scope of research to identify potential targets in the treatment of retinal disease. PMID:25722474

  18. Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease

    PubMed Central

    Beltran, William A.; Cideciyan, Artur V.; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S.; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

    2015-01-01

    Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

  19. Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease.

    PubMed

    Beltran, William A; Cideciyan, Artur V; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L; Lewin, Alfred S; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

    2015-10-27

    Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

  20. Non-enzymatic glycation of α-crystallin as an in vitro model for aging, diabetes and degenerative diseases.

    PubMed

    Karumanchi, Devi Kalyan; Karunaratne, Nuwan; Lurio, Laurence; Dillon, James P; Gaillard, Elizabeth R

    2015-12-01

    Alpha crystallin, a small heat-shock protein, has been studied extensively for its chaperone function. Alpha crystallin subunits are expressed in stress conditions and have been found to prevent apoptosis by inhibiting the activation of caspase pathway. Non-enzymatic glycation of protein leads to the formation of advanced glycation end-products (AGEs). These AGEs bind to receptors and lead to blocking the signaling pathways or cause protein precipitation as observed in aggregation-related diseases. Methylglyoxal (MGO) is one of the major glycating agents expressed in pathological conditions due to defective glycolysis pathway. MGO reacts rapidly with proteins, forms AGEs and finally leads to aggregation. The goal of this study was to understand the non-enzymatic glycation-induced structural damage in alpha crystallin using biophysical and spectroscopic characterization. This will help to develop better disease models for understanding the biochemical pathways and also in drug discovery. PMID:26215735

  1. Detection of Retinal Nerve Fiber Layer Defects in Alzheimer’s Disease Using SD-OCT

    PubMed Central

    Kromer, Robert; Serbecic, Nermin; Hausner, Lucrezia; Froelich, Lutz; Aboul-Enein, Fahmy; Beutelspacher, Sven C.

    2014-01-01

    Introduction: Our aim is to examine the clinical value of spectral-domain optical coherence tomography (Spectralis OCT) to detect retinal nerve fibre layer defects in patients with clinically defined Alzheimer‘s disease (AD). Material and Methods: This cross-sectional study included 22 patients with AD (mean age: 75.9 ± 6.1 years) and 22 healthy age- and sex-matched controls. Neuro-ophthalmologic examinations and a series of high-resolution OCT examinations of the peripapillary retinal nerve fiber layer (RNFL) thickness using the Spectralis 3.5-mm circle scan protocol with ART-Modus and eye tracking were obtained, and compared to age- and sex-matched healthy control subjects. Results: Patients with AD showed a significant decrease in RNFL thickness in the nasal superior sector compared to the control group (101.0 ± 18.18 μm versus 122.8 ± 28.08 μm; P < 0.0001). In all other sectors, independently of disease duration, no significant difference in RNFL thickness compared to controls was detected. Using the advanced age- and gender-matched measurement model, 32 out of 42 eyes (76.19%) as pathologic with 67 abnormal sectors were detected. Discussion: As examined by spectral-domain OCT, patients with mild to moderate stages of AD showed a significant reduction of RNFL thickness in the nasal superior sector. Nevertheless, successive studies are needed. PMID:24616709

  2. An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.

    PubMed

    Sung, J H; Ramirez-Lassepas, M; Mastri, A R; Larkin, S M

    1980-03-01

    A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder. PMID:6154779

  3. Measurement of Intervertebral Motion Using Quantitative Fluoroscopy: Report of an International Forum and Proposal for Use in the Assessment of Degenerative Disc Disease in the Lumbar Spine

    PubMed Central

    Breen, Alan C.; Teyhen, Deydre S.; Mellor, Fiona E.; Breen, Alexander C.; Wong, Kris W. N.; Deitz, Adam

    2012-01-01

    Quantitative fluoroscopy (QF) is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong), over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls. PMID:22666606

  4. Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review.

    PubMed

    Attard, Everaldo; Martinoli, Maria-Grazia

    2015-01-01

    A growing number of studies have revealed that natural molecules own interesting antioxidant and anti-apoptotic properties in cell culture as well as in animal models of human diseases such as cancer, inflammatory and neurodegenerative diseases. During the past sixty years, several cucurbitacins have been isolated from a number of cucurbitaceous species, amongst others. Cucurbitacins are triterpenoid compounds originally identify as the bitter components of the Cucurbit family that demonstrated several pro-survival activities in various model of cellular decay. Specifically, Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid, has been investigated in a wider array of bioactivities, mainly immunomodulatory. Recently, CuE has been reported to possess anti-inflammatory and anti-tumorigenic properties mediated by its action on the cellular cytoskeleton, on mitotic pathways as well as on cellular autophagy. Few studies also pinpoint the role of CuE in the nervous system as cytostatic for gliomas and neuroprotective in a model of Parkinson's diseases. This review deals with the use of CuE in various experimental models as one of the most promising therapeutic natural molecules against cancer proliferation, as an immunomudulator and for the prevention of neurodegeneration. PMID:25915611

  5. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.

    PubMed

    Ames, Bruce N

    2006-11-21

    Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life. PMID:17101959

  6. Inherited retinal diseases in dogs: advances in gene/mutation discovery

    PubMed Central

    Miyadera, Keiko

    2015-01-01

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed. PMID:26120276

  7. Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model

    PubMed Central

    Park, Un Chul; Cho, Myung Soo; Park, Jung Hyun; Kim, Sang Jin; Ku, Seung-Yup; Choi, Young Min; Moon, Shin Yong

    2011-01-01

    Objective To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells (105 cells/5 µL) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease. PMID:22384445

  8. [Application of retinal oximeter in ophthalmology].

    PubMed

    Li, Jing; Ma, Jianmin; Wang, Ningli

    2015-11-01

    Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed. PMID:26850588

  9. Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases.

    PubMed

    Sprengelmeyer, R; Canavan, A G; Lange, H W; Hömberg, V

    1995-01-01

    The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop. PMID:7885356

  10. A Chaplain-led Spiritual Life Review Pilot Study for Patients with Brain Cancers and Other Degenerative Neurologic Diseases

    PubMed Central

    Piderman, Katherine M.; Breitkopf, Carmen Radecki; Jenkins, Sarah M.; Euerle, Terin T.; Lovejoy, Laura A.; Kwete, Gracia M.; Jatoi, Aminah

    2015-01-01

    Objective: This pilot study was designed to describe changes in spiritual well-being (SWB), spiritual coping, and quality of life (QOL) in patients with brain cancer or other neurodegenerative diseases participating in a chaplain-led spiritual life review interview and development of a spiritual legacy document (SLD). Methods: Eligible participants were enrolled and completed baseline questionnaires. They were interviewed by a board-certified chaplain about spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD was prepared for each participant, and one month follow-up questionnaires were completed. Two cases are summarized, and spiritual development themes are illustrated within a spiritual development framework. Results: A total of 27 patients completed baseline questionnaires and the interview; 24 completed the SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious coping, and QOL were detected. The majority maintained the highest (best) scores of negative religious coping, demonstrating minimal spiritual struggle. Conclusions: Despite the challenges of brain cancers and other neurodegenerative diseases, participants demonstrated improvements in SWB, positive religious coping, and QOL. Patient comments indicate that benefit is related to the opportunity to reflect on and integrate spiritual experiences and to preserve them for others. Research with a larger, more diverse sample is needed, as well as clinical applications for those too vulnerable to participate in longitudinal follow-up. PMID:25973267

  11. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    PubMed

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases. PMID:27072643

  12. Evidence from Raman Spectroscopy of a Putative Link Between Inherent Bone Matrix Chemistry and Degenerative Joint Disease

    PubMed Central

    Kerns, Jemma G; Gikas, Panagiotis D; Buckley, Kevin; Shepperd, Adam; Birch, Helen L; McCarthy, Ian; Miles, Jonathan; Briggs, Timothy W R; Keen, Richard; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

    2014-01-01

    Objective Osteoarthritis (OA) is a common debilitating disease that results in degeneration of cartilage and bone in the synovial joints. Subtle changes in the molecular structure of the subchondral bone matrix occur and may be associated with cartilage changes. The aim of this study was to explore whether the abnormal molecular changes observed in the matrix of OA subchondral bone can be identified with Raman spectroscopy. Methods Tibial plateaus from patients undergoing total knee replacement for OA (n = 10) were compared with healthy joints from patients undergoing leg amputation (n = 5; sex- and laterality-matched) and with non-OA cadaveric knee specimens (n = 5; age-matched). The samples were analyzed with Raman spectroscopy, peripheral quantitative computed tomography, and chemical analysis to compare changes in defined load-bearing sites in both the medial and lateral compartments. Results OA subchondral bone matrix changes were detected by Raman spectroscopy. Within each cohort, there was no spectral difference in bone matrix chemistry between the medial and lateral compartments, whereas a significant spectral difference (P < 0.001) was observed between the non-OA and OA specimens. Type I collagen chain ratios were normal in the non-OA specimens but were significantly elevated in the OA specimens. Conclusion In comparing the results of Raman spectroscopy with those obtained by other standard techniques, these findings show, for the first time, that subchondral bone changes, or inherent differences, exist in both the medial and lateral (beneath intact cartilage) compartments of OA knees. The development of Raman spectroscopy as a screening tool, based on molecular-specific modifications in bone, would facilitate the identification of clinical disease, including early molecular changes. PMID:24470432

  13. Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro

    PubMed Central

    Martins, João; Elvas, Filipe; Brudzewsky, Dan; Martins, Tânia; Kolomiets, Bogdan; Tralhão, Pedro; Gøtzsche, Casper R.; Cavadas, Cláudia; Castelo-Branco, Miguel; Woldbye, David P. D.; Picaud, Serge; Santiago, Ana R.

    2015-01-01

    Neuropeptide Y (NPY) is expressed in mammalian retina but the location and potential modulatory effects of NPY receptor activation remain largely unknown. Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative diseases, particularly glaucoma. Using purified RGCs and ex vivo rat retinal preparations, we have measured RGC intracellular free calcium concentration ([Ca2+]i) and RGC spiking activity, respectively. We found that NPY attenuated the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor activation. Moreover, (Leu31, Pro34)−NPY, a Y1/Y5 receptor agonist, increased the initial burst response of OFF-type RGCs, although no effect was observed on RGC spontaneous spiking activity. The Y1 receptor activation was also able to directly modulate RGC responses by attenuating the NMDA-induced increase in RGC spiking activity. These results suggest that Y1 receptor activation, at the level of inner or outer plexiform layers, leads to modulation of RGC receptive field properties. Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death. However, in an animal model of retinal ischemia-reperfusion injury, pretreatment with NPY or (Leu31, Pro34)−NPY was not able to prevent apoptosis or rescue RGCs. In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective actions detected in retinal explants can be translated into animal models of retinal degenerative diseases. PMID:26311075

  14. A CMOS active pixel sensor for retinal stimulation

    NASA Astrophysics Data System (ADS)

    Prydderch, Mark L.; French, Marcus J.; Mathieson, Keith; Adams, Christopher; Gunning, Deborah; Laudanski, Jonathan; Morrison, James D.; Moodie, Alan R.; Sinclair, James

    2006-02-01

    Degenerative photoreceptor diseases, such as age-related macular degeneration and retinitis pigmentosa, are the most common causes of blindness in the western world. A potential cure is to use a microelectronic retinal prosthesis to provide electrical stimulation to the remaining healthy retinal cells. We describe a prototype CMOS Active Pixel Sensor capable of detecting a visual scene and translating it into a train of electrical pulses for stimulation of the retina. The sensor consists of a 10 x 10 array of 100 micron square pixels fabricated on a 0.35 micron CMOS process. Light incident upon each pixel is converted into output current pulse trains with a frequency related to the light intensity. These outputs are connected to a biocompatible microelectrode array for contact to the retinal cells. The flexible design allows experimentation with signal amplitudes and frequencies in order to determine the most appropriate stimulus for the retina. Neural processing in the retina can be studied by using the sensor in conjunction with a Field Programmable Gate Array (FPGA) programmed to behave as a neural network. The sensor has been integrated into a test system designed for studying retinal response. We present the most recent results obtained from this sensor.

  15. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  16. Diagnostic dilemma of degenerative joint disease, chronic avascular necrosis or metastasis in planar Tc-99m-methylene diphosphonate planar skeletal scintigraphy excluded by single positron emission computed tomography/computed tomography

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Basher, Rajender Kumar; Kumar, Narendra; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a 71-year-old male patient subjected to skeletal scintigraphy for metastasis work up of prostate cancer. Whole body planar images revealed a solitary focal tracer uptake in left femoral head mimicking as solitary metastatic focus. Single positron emission computed tomography/computed tomography images localized this increased tracer uptake to the subchondral cysts with minimal sclerosis in left femur head with no decrease in size of femur head and was reported as (degenerative joint disease). PMID:26170582

  17. Degenerative cervical myelopathy.

    PubMed

    Kato, So; Fehlings, Michael

    2016-09-01

    Cervical myelopathy is the most common cause of acquired spinal cord compromise. The concept of degenerative cervical myelopathy (DCM), defined as symptomatic myelopathy associated with degenerative arthropathic changes in the spine axis, is being introduced. Given its progressive nature, treatment options have to be chosen in a timely manner. Surgical options include anterior discectomy and fusion (ACDF), anterior corpectomy and fusion (ACCF), arthroplasty (in highly select cases), posterior laminectomy with/without fusion, and laminoplasty. Indications for each should be carefully considered in individual patients. Riluzole, a sodium-glutamate antagonist, is a promising option to optimize neurologic outcomes post-surgery and is being examined in the CSM-Protect Randomized Controlled Trial. Preoperative risk assessment is mandatory for prognostication. Sagittal alignment is known to play an important role to optimize surgical outcome. Guidelines for optimal management of DCM are in process. In principle, all but the mildest cases of DCM should be offered surgery for optimal outcome. PMID:27250040

  18. D-penicillamine Induced Degenerative Dermopathy

    PubMed Central

    Khandpur, Sujay; Jain, Naresh; Singla, Shweta; Chatterjee, Priti; Behari, Madhuri

    2015-01-01

    D-penicillamine interferes with elastin and collagen metabolism and produces several cutaneous and multi-systemic side-effects. We present two cases of Wilson's disease who on long-term penicillamine therapy developed drug-induced degenerative dermopathy manifesting as skin fragility over pressure sites and cutis laxa-like changes. PMID:26288416

  19. Photovoltaic retinal prosthesis: implant fabrication and performance

    NASA Astrophysics Data System (ADS)

    Wang, Lele; Mathieson, K.; Kamins, T. I.; Loudin, J. D.; Galambos, L.; Goetz, G.; Sher, A.; Mandel, Y.; Huie, P.; Lavinsky, D.; Harris, J. S.; Palanker, D. V.

    2012-08-01

    The objective of this work is to develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 µm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 µm wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280, 140 and 70 µm) with active electrodes of 80, 40 and 20 µm diameter were fabricated. The turn-on voltages of the one-diode, two-series-connected diode and three-series-connected diode structures are approximately 0.6, 1.2 and 1.8 V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ˜0.36 A W-1, at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution.

  20. Degenerative Spinal Deformity.

    PubMed

    Ailon, Tamir; Smith, Justin S; Shaffrey, Christopher I; Lenke, Lawrence G; Brodke, Darrel; Harrop, James S; Fehlings, Michael; Ames, Christopher P

    2015-10-01

    Degenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22°, and lumbopelvic mismatch <±9°; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes. PMID:26378361

  1. Posterior Interspinous Fusion Device for One-Level Fusion in Degenerative Lumbar Spine Disease : Comparison with Pedicle Screw Fixation - Preliminary Report of at Least One Year Follow Up

    PubMed Central

    Kim, Ho Jung; Chun, Hyoung Joon; Oh, Suck Jun; Kang, Tae Hoon; Yang, Moon Sool

    2012-01-01

    Objective Transpedicular screw fixation has some disadvantages such as postoperative back pain through wide muscle dissection, long operative time, and cephalad adjacent segmental degeneration (ASD). The purposes of this study are investigation and comparison of radiological and clinical results between interspinous fusion device (IFD) and pedicle screw. Methods From Jan. 2008 to Aug. 2009, 40 patients underwent spinal fusion with IFD combined with posterior lumbar interbody fusion (PLIF). In same study period, 36 patients underwent spinal fusion with pedicle screw fixation as control group. Dynamic lateral radiographs, visual analogue scale (VAS), and Korean version of the Oswestry disability index (K-ODI) scores were evaluated in both groups. Results The lumbar spine diseases in the IFD group were as followings; spinal stenosis in 26, degenerative spondylolisthesis in 12, and intervertebral disc herniation in 2. The mean follow up period was 14.24 months (range; 12 to 22 months) in the IFD group and 18.3 months (range; 12 to 28 months) in pedicle screw group. The mean VAS scores was preoperatively 7.16±2.1 and 8.03±2.3 in the IFD and pedicle screw groups, respectively, and improved postoperatively to 1.3±2.9 and 1.2±3.2 in 1-year follow ups (p<0.05). The K-ODI was decreased significantly in an equal amount in both groups one year postoperatively (p<0.05). The statistics revealed a higher incidence of ASD in pedicle screw group than the IFD group (p=0.029). Conclusion Posterior IFD has several advantages over the pedicle screw fixation in terms of skin incision, muscle dissection and short operative time and less intraoperative estimated blood loss. The IFD with PLIF may be a favorable technique to replace the pedicle screw fixation in selective case. PMID:23133725

  2. Increasing Incidence of Degenerative Spinal Diseases in Japan during 25 Years: The Registration System of Spinal Surgery in Tohoku University Spine Society.

    PubMed

    Aizawa, Toshimi; Kokubun, Shoichi; Ozawa, Hiroshi; Kusakabe, Takashi; Tanaka, Yasuhisa; Hoshikawa, Takeshi; Hashimoto, Ko; Kanno, Haruo; Morozumi, Naoki; Koizumi, Yutaka; Sato, Tetsuro; Hyodo, Hironori; Kasama, Fumio; Ogawa, Shinji; Murakami, Eiichi; Kawahara, Chikashi; Yahata, Jun-Ichiro; Ishii, Yushin; Itoi, Eiji

    2016-01-01

    Spinal disorders affect mainly older people and cause pain, paralysis and/or deformities of the trunk and/or extremities, which could eventually disturb locomotive functions. For ensuring safe and high-quality treatment of spinal disorders, in 1987, the Tohoku University Spine Society (TUSS) was established by orthopedic departments in Tohoku University School of Medicine and its affiliated hospitals in and around Miyagi Prefecture. All spine surgeries have been enrolled in the TUSS Spine Registry since 1988. Using the data from this registration system between 1988 and 2012, we demonstrate here the longitudinal changes in surgical trends for spinal disorders in Japan that has rushed into the most advanced "aging society" in the world. In total, data on 56,744 surgeries were retrieved. The number of spinal surgeries has annually increased approximately 4-fold. There was a particular increase among patients aged ≥ 70 years and those aged ≥ 80 years, with a 20- to 90-fold increase. Nearly 90% of the spinal operations were performed for degenerative disorders, with their number increasing approximately 5-fold from 705 to 3,448. The most common disease for surgery was lumbar spinal stenosis (LSS) (35.9%), followed by lumbar disc herniation (27.7%) and cervical myelopathy (19.8%). In 2012, approximately half of the patients with LSS and cervical myelopathy were ≥ 70 years of age. In conclusion, the number of spinal operations markedly increased during the 25-year period, particularly among older patients. As Japan has a notably aged population, the present study could provide a near-future model for countries with aging population. PMID:26876801

  3. Surgical Outcome Predictor in Degenerative Lumbar Spinal Disease Based on Health Related Quality of Life Using Euro-Quality 5 Dimensions Analysis

    PubMed Central

    Lee, Byung Ho; Yang, Jae-Ho; Lee, Hwan-Mo; Park, Jun-Young; Park, Sang-Eun

    2016-01-01

    Purpose We aim to introduce the predictive value of a quantitatively described formula model in a multicenter prospective analysis using the EuroQol-5 dimensions (EQ-5D) health scale to anticipate postoperative improvement in patients with degenerative lumbar spine disease (DLSD). Materials and Methods Quality of life was evaluated in 376 patients from 17 tertiary hospitals before and after spinal decompression and fusion surgery. The five items of the EQ-5D, mobility (M), self-care (S), usual activities (A), pain/discomfort (P), and anxiety/depression (D), were checked as level 1, 2, or 3, with 3 being the worst. A minimal significant change in the calculated EQ-5D (cEQ-5D) was set as 0.05. Logistic regression analysis was performed to predict the highest successful outcome (cEQ-5D improvement after operation >0.05) with the given sets of 5 items of the EQ-5D. Results In the cEQ-5D analysis, among patients with a formula score of S+A+2×P+D≤8, 18/68 (27%) showed significant improvement in the cEQ-5D at 1 year postoperatively (p<0.05). However, in patients with a formula score of ≥9, 265/308 (86%) demonstrated significant improvements in the cEQ-5D at 1 year postoperatively (p<0.05). Conclusion We suggest that S+A+2×P+D≥9 in the EQ-5D can quantitatively describe the better surgical outcome predictors for DLSD. With a definite DLSD lesion confirmed by an imaging study, patients who meet the formula scores of 9 or over and have refractory symptoms to non-operative treatment could be better surgical candidates resulting in satisfactory surgical outcomes of over 86%, than those who scored 8 or lower. PMID:27401654

  4. Long-term Follow-up (Minimum 5 Years) Study of Single-level Posterior Dynamic Stabilization in Lumbar Degenerative Disease; 'Interspinous U' & 'DIAM'

    PubMed Central

    Kim, Yeon Joon; Park, Chan Woo; Son, Seong; Kim, Woo Kyung

    2012-01-01

    Objectives Recently posterior dynamic stabilizations (PDS) are increased in degenerative lumbar disease. But, some previous studies had doubts its long term prognosis. Long term clinical and radiological results of PDS using interspinous device (Interspinous U, DIAM) were analyzed. Methods We have used the 'interspinous U' and 'DIAM' for patients with lumbar spinal stenosis. We included single level lumbar spinal stenosis patients who completed minimum 60 months follow-up evaluation. All patients checked plain lateral and flexion-extension views at immediately after the surgery and each follow-up. The clinical outcome was measured by Odom's criteria. Complications including post operative infection, bony erosion, device fracture, device malformations, and instabilities were surveyed. Results We included 18 for 'Interspinous U' and 7 patients 'DIAM' groups. Mean follow-up durations for 'Interspinous U' and 'DIAM' were 74.6 and 62.6 months, respectively. Satisfactory groups were 50.0% and 42.9 % for 'Interspinous U' and 'DIAM' groups. In 'Interspinous U' group disc height ratio increased transiently in immediate postoperative period (from 0.18 to 0.21) and then, decreased significantly in last follow-up (0.18). In 'DIAM' group, disc height ratio increased transiently in immediate postoperative period (from 0.18 to 0.19), and then decreased significantly in the last follow-up (0.16). Three (16.7%) and two (28.6%) patients undergo on a re-operation due to severe back pain in 'Interspinous U' and 'DIAM' groups. Conclusion Long term follow up 'Interspinous U' and 'DIAM' group showed low patient satisfaction and poor radiological outcomes. To ascertain the benefit of PDS compare with posterior screw fixation, prospective analysis with larger population and multi-center study will be needed. PMID:25983797

  5. Clinical and radiologic comparison of dynamic cervical implant arthroplasty and cervical total disc replacement for single-level cervical degenerative disc disease.

    PubMed

    Shichang, Liu; Yueming, Song; Limin, Liu; Lei, Wang; Zhongjie, Zhou; Chunguang, Zhou; Xi, Yang

    2016-05-01

    Anterior cervical discectomy and fusion, to date the most successful spine procedure for the surgical treatment of cervical radiculopathy, has limitations that have led to the development of non-fusion cervical procedures, such as cervical total disc replacement (TDR) and dynamic cervical implant (DCI) arthroplasty. We compared the clinical and radiological results of DCI and cervical TDR for the treatment of single-level cervical degenerative disc disease in Chinese patients. A retrospective review of 179 patients with cervical spondylotic myelopathy who underwent DCI or TDR between April 2010 and October 2012 was conducted, and 152 consecutive patients (67 patients single-level DCI and 85 single-level TDR) who completed at least 2years of follow-up were included. Clinical and radiological assessments were performed preoperatively and at 1week and 3, 6, 12, and 24months postoperatively. The most common operative level was C5/C6 (49.3%). The differences in blood loss, duration of surgery, and duration of hospitalization were not statistically significant. The Japanese Orthopaedic Association scale, Visual Analog Scale, Neck Disability Index, and Short Form-36 scores improved significantly after surgery in both the DCI and TDR groups (P<0.05), but the differences were not statistically significant at the final follow-up. The rate of occurrence of heterotopic ossification was 22.4% and 28.2% in the DCI and TDR groups, respectively. As an effective non-fusion technique, DCI is a more economical procedure. Further prospective, randomized studies with long-term follow-up periods are needed to determine the long-term effects. PMID:26928156

  6. A case of von Hippel-Lindau disease with juxtapapillary retinal capillary hemangioma and nutcracker phenomenon.

    PubMed

    Yavaş, Güliz Fatma; Okur, Nazan; Küsbeci, Tuncay; Norman, Esma; Inan, Ümit

    2013-06-01

    The aim of this study was to evaluate a patient with von Hippel-Lindau (VHL) syndrome and to discuss the clinical manifestations. A 25-year-old woman presented to our clinic with blurred vision for 2 months. Best corrected visual acuity in right eye was 20/50, and fundoscopic examination revealed juxtapapillary endophytic retinal capillary hemangioma. Examination findings on left eye were normal. On optical coherence tomography, exudation was prominent on macula. History revealed cerebellar operation because of cerebellar hemangioblastoma. On abdominal ultrasonography, liver hemangiomas and pancreatic cysts were seen, confirmed by abdominal computerized tomography (CT). Abdominal CT imaging also revealed nutcracker phenomenon. Transthoracic echocardiography showed atrial septal aneurysm without shunt. The patient refused ocular treatment. At 3-month control, ophthalmic findings were the same. To our knowledge, this is the first case of VHL disease reported to be associated with nutcracker phenomenon and atrial septal aneurysm. Systemic evaluation and regular follow-up should be recommended to subjects with VHL disease. PMID:23114531

  7. The retinal ciliopathies.

    PubMed

    Adams, N A; Awadein, Ahmed; Toma, Hassanain S

    2007-09-01

    While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present. PMID:17896309

  8. Finite element modeling of retinal prosthesis mechanics

    NASA Astrophysics Data System (ADS)

    Basinger, B. C.; Rowley, A. P.; Chen, K.; Humayun, M. S.; Weiland, J. D.

    2009-10-01

    Epiretinal prostheses used to treat degenerative retina diseases apply stimulus via an electrode array fixed to the ganglion cell side of the retina. Mechanical pressure applied by these arrays to the retina, both during initial insertion and throughout chronic use, could cause sufficient retinal damage to reduce the device's effectiveness. In order to understand and minimize potential mechanical damage, we have used finite element analysis to model mechanical interactions between an electrode array and the retina in both acute and chronic loading configurations. Modeling indicates that an acute tacking force distributes stress primarily underneath the tack site and heel edge of the array, while more moderate chronic stresses are distributed more evenly underneath the array. Retinal damage in a canine model chronically implanted with a similar array occurred in correlating locations, and model predictions correlate well with benchtop eyewall compression tests. This model provides retinal prosthesis researchers with a tool to optimize the mechanical electrode array design, but the techniques used here represent a unique effort to combine a modifiable device and soft biological tissues in the same model and those techniques could be extended to other devices that come into mechanical contact with soft neural tissues.

  9. [The revolution in the treatment of retinal diseases: anti-VEGF treatment at the Assuta Eye Institute].

    PubMed

    Katz, Gabriel; Zehavi, Chaya; Treister, Giora

    2015-04-01

    The VEGF protein (Vascular Endothelial Growth Factor) was identified in the '80s as a factor which induces proliferation of blood vessels in the body in general and in the retina in particular. Proliferative processes in retinal blood vessels, vascular permeability and induced edema which follows, frequently cause blindness in the diseases of the macula: AMD (Age-related Macular Degeneration) diabetes and retinal vascular occlusions. Since 2006, through treatment using anti-VEGF drugs--Avastin (Bevacizumab) and Lucentis (Ranibizumab) and Eylea (Aflibercept)--blindness in many patients in Israel and elsewhere was prevented. This paper reviews the treatment with anti-VEGF intraocular injections in the above mentioned diseases with reference to the growing activity at the Assuta Eye Institute. PMID:26065226

  10. Review of the role of refined dietary sugars (fructose and glucose) in the genesis of retinal disease.

    PubMed

    Kearney, Frances M; Fagan, Xavier J; Al-Qureshi, Salmaan

    2014-08-01

    This review examines the current evidence of the relationship between sugar consumption and the development of retinal and other eye diseases including diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataract. Sucrose is comprised of fructose and glucose. Sugar consumption has increased five-fold over the last century, with high quantities of sucrose and high-fructose corn syrup found in processed food and soft drinks. This increased consumption is increasingly recognized as a central factor in the rapidly rising rates of obesity and type 2 diabetes. The body metabolizes fructose and glucose differently, with fructose appearing to have the greater propensity to contribute to the metabolic syndrome. This review examines the effect of high rates of dietary consumption of refined carbohydrates on the eye, including the effect of chronic hyperglycaemia on microvascular disease in diabetic retinopathy, and the pathophysiological changes in the retinal circulation in hypertensive retinopathy. PMID:24373051

  11. VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis

    PubMed Central

    Huang, Delong; Zhao, Chen; Ju, Rong; Kumar, Anil; Tian, Geng; Huang, Lijuan; Zheng, Lei; Li, Xianglin; Liu, Lixian; Wang, Shasha; Ren, Xiangrong; Ye, Zhimin; Chen, Wei; Xing, Liying; Chen, Qishan; Gao, Zhiqin; Mi, Jia; Tang, Zhongshu; Wang, Bin; Zhang, Shuping; Lee, Chunsik; Li, Xuri

    2016-01-01

    Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration. PMID:27189805

  12. VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

    PubMed

    Huang, Delong; Zhao, Chen; Ju, Rong; Kumar, Anil; Tian, Geng; Huang, Lijuan; Zheng, Lei; Li, Xianglin; Liu, Lixian; Wang, Shasha; Ren, Xiangrong; Ye, Zhimin; Chen, Wei; Xing, Liying; Chen, Qishan; Gao, Zhiqin; Mi, Jia; Tang, Zhongshu; Wang, Bin; Zhang, Shuping; Lee, Chunsik; Li, Xuri

    2016-01-01

    Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration. PMID:27189805

  13. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  14. Photoreceptor cell death and rescue in retinal detachment and degenerations

    PubMed Central

    Murakami, Yusuke; Notomi, Shoji; Hisatomi, Toshio; Nakazawa, Toru; Ishibashi, Tatsuro; Miller, Joan W.; Vavvas, Demetrios G.

    2013-01-01

    Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss. PMID:23994436

  15. Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease

    PubMed Central

    Ellingford, Jamie M.; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G.; Sergouniotis, Panagiotis I.; O'Sullivan, James; Lamb, Janine A.; Perveen, Rahat; Hall, Georgina; Newman, William G.; Bishop, Paul N.; Roberts, Stephen A.; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C.; Nemeth, Andrea H.; Black, Graeme C.M.

    2016-01-01

    Purpose To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Design Case series. Participants A total of 562 patients diagnosed with IRD. Methods We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Main Outcome Measures Diagnostic yield of genomic testing. Results Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15–45) uplift in diagnostic yield. Conclusions We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. PMID:26872967

  16. From retinal circuitry to eye diseases -- in memory of Henk Spekreijse

    PubMed Central

    Wu, Samuel M.

    2009-01-01

    This article summarizes our recent works on stratum-by-stratum structure-function rules for synaptic contacts between retinal bipolar cells and third-order retinal neurons in the inner plexiform layer. These rules were derived from large-scale voltage clamp recordings of various types of bipolar cells in the tiger salamander retina, and they appear applicable to bipolar cells in the mouse and other mammalian species. This review also gives a brief account of how we used pathway-specific knockout mouse models to dissect rod and cone signaling channels in the mammalian retina. Furthermore, studies on cellular and genetic mechanisms underlying several neurodegenerative retinal disorders are described. PMID:18948133

  17. Severity of coronary artery disease and retinal microvascular signs in patients with diagnosed versus undiagnosed diabetes: cross-sectional study

    PubMed Central

    Phan, Kevin; Mitchell, Paul; Liew, Gerald; Plant, Adam J.; Wang, Sarah B.; Xu, Joshua; Chiha, Joseph; Thiagalingam, Aravinda; Burlutsky, George

    2016-01-01

    Background There is increasing evidence that a considerable proportion of patients with diabetes remain undiagnosed and untreated, however, it is unclear whether this is associated with more severe coronary artery disease (CAD) and microvasculature changes compared with diagnosed patients. We assessed CAD extent and severity, along with changes to the retinal microvascular structure in participants with undiagnosed versus diagnosed type 2 diabetes. Methods Participants of the Australian Heart Eye Study were stratified into participants with previously diagnosed diabetes (n=489), undiagnosed diabetes (n=76) and no diabetes (n=1,112). Retinal vessel caliber was measured from digital retinal images. Extent and severity of CAD was assessed using Extent and Gensini scores from angiography findings, respectively. Results Participants with undiagnosed and diagnosed diabetes versus those with no diabetes (reference group) had increased odds of being in the highest quartile of Gensini scores, multivariate adjusted odds ratios (OR) =7.02 [95% confidence interval (CI), 2.04–24.1] and OR =2.76 (95% CI, 1.67–4.55), respectively. Participants with undiagnosed and diagnosed diabetes versus those with no diabetes also had increased odds of being in the highest quartile of Extent scores, multivariate adjusted OR =7.63 (95% CI, 2.15–27.10) and OR =3.72 (95% CI, 2.22–6.27), respectively. No significant differences were observed in retinal vessel caliber between participants with undiagnosed versus diagnosed diabetes. Conclusions The present study demonstrated that participants with undiagnosed diabetes compared to those with previously diagnosed diabetes, had a stronger likelihood of having more severe and extensive CAD. However, retinal microvascular signs did not differ by diabetes status. PMID:27499940

  18. Clustered Regularly Interspaced Short Palindromic Repeats: Challenges in Treating Retinal Disease.

    PubMed

    Chrenek, Micah A; Nickerson, John M; Boatright, Jeffrey H

    2016-01-01

    Ophthalmic researchers and clinicians arguably have led the way for safe, effective gene therapy, most notably with adeno-associated viral gene supplementation in the treatment for patients with Leber congenital amaurosis type 2 with mutations in the RPE65 gene. These successes notwithstanding, most other genetic retinal disease will be refractory to supplementation. The ideal gene therapy approach would correct gene mutations to restore normal function in the affected cells. Gene editing in which a mutant allele is inactivated or converted to sequence that restores normal function is hypothetically one such approach. Such editing involves site-specific digestion of mutant genomic DNA followed by repair. Previous experimental approaches were hampered by inaccurate and high rates of off-site lesioning and by overall low digestion rates. A new tool, clustered regularly interspaced short palindromic repeats coupled with the nuclease Cas9, may address both shortcomings. Some of the many challenges that must be addressed in moving clustered regularly interspaced short palindromic repeats coupled with the nuclease Cas9 therapies to the ophthalmic clinic are discussed here. PMID:27488072

  19. Fast localization of optic disc and fovea in retinal images for eye disease screening

    NASA Astrophysics Data System (ADS)

    Yu, H.; Barriga, S.; Agurto, C.; Echegaray, S.; Pattichis, M.; Zamora, G.; Bauman, W.; Soliz, P.

    2011-03-01

    Optic disc (OD) and fovea locations are two important anatomical landmarks in automated analysis of retinal disease in color fundus photographs. This paper presents a new, fast, fully automatic optic disc and fovea localization algorithm developed for diabetic retinopathy (DR) screening. The optic disc localization methodology comprises of two steps. First, the OD location is identified using template matching and directional matched filter. To reduce false positives due to bright areas of pathology, we exploit vessel characteristics inside the optic disc. The location of the fovea is estimated as the point of lowest matched filter response within a search area determined by the optic disc location. Second, optic disc segmentation is performed. Based on the detected optic disc location, a fast hybrid level-set algorithm which combines the region information and edge gradient to drive the curve evolution is used to segment the optic disc boundary. Extensive evaluation was performed on 1200 images (Messidor) composed of 540 images of healthy retinas, 431 images with DR but no risk of macular edema (ME), and 229 images with DR and risk of ME. The OD location methodology obtained 98.3% success rate, while fovea location achieved 95% success rate. The average mean absolute distance (MAD) between the OD segmentation algorithm and "gold standard" is 10.5% of estimated OD radius. Qualitatively, 97% of the images achieved Excellent to Fair performance for OD segmentation. The segmentation algorithm performs well even on blurred images.

  20. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report

    PubMed Central

    Weiss, Jeffrey N.; Levy, Steven; Malkin, Alexis

    2015-01-01

    In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS. PMID:26199618

  1. Cytomegalovirus retinitis

    MedlinePlus

    ... to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References Crumpacker CS. ... 5. Read More Antibody HIV/AIDS Immune response Retinal detachment Systemic WBC count Update Date 12/10/ ...

  2. Retinal dystrophies, genomic applications in diagnosis and prospects for therapy.

    PubMed

    Nash, Benjamin M; Wright, Dale C; Grigg, John R; Bennetts, Bruce; Jamieson, Robyn V

    2015-04-01

    Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. This review aims to demonstrate the high degree of genetic complexity in both the causative disease genes and their associated phenotypes, highlighting the more common clinical manifestation of retinitis pigmentosa (RP). The review also provides insight to recent advances in genomic molecular diagnosis and gene and cell-based therapies for the RDs. PMID:26835369

  3. Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration.

    PubMed

    Fernández-Sánchez, Laura; Lax, Pedro; Noailles, Agustina; Angulo, Antonia; Maneu, Victoria; Cuenca, Nicolás

    2015-01-01

    All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases. PMID:26263962

  4. TU-C-12A-12: Differentiating Bone Lesions and Degenerative Joint Disease in NaF PET/CT Scans Using Machine Learning

    SciTech Connect

    Perk, T; Bradshaw, T; Muzahir, S; Jeraj, R; Meyer, E

    2014-06-15

    Purpose: [F-18]NaF PET can be used to image bone metastases; however, tracer uptake in degenerative joint disease (DJD) often appears similar to metastases. This study aims to develop and compare different machine learning algorithms to automatically identify regions of [F-18]NaF scans that correspond to DJD. Methods: 10 metastatic prostate cancer patients received whole body [F-18]NaF PET/CT scans prior to treatment. Image segmentation resulted in 852 ROIs, 69 of which were identified by a nuclear medicine physician as DJD. For all ROIs, various PET and CT textural features were computed. ROIs were divided into training and testing sets used to train eight different machine learning classifiers. Classifiers were evaluated based on receiver operating characteristics area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV). We also assessed the added value of including CT features in addition to PET features for training classifiers. Results: The training set consisted of 37 DJD ROIs with 475 non-DJD ROIs, and the testing set consisted of 32 DJD ROIs with 308 non-DJD ROIs. Of all classifiers, generalized linear models (GLM), decision forests (DF), and support vector machines (SVM) had the best performance. AUCs of GLM (0.929), DF (0.921), and SVM (0.889) were significantly higher than the other models (p<0.001). GLM and DF, overall, had the best sensitivity, specificity, and PPV, and gave a significantly better performance (p<0.01) than all other models. PET/CT GLM classifiers had higher AUC than just PET or just CT. GLMs built using PET/CT information had superior or comparable sensitivities, specificities and PPVs to just PET or just CT. Conclusion: Machine learning algorithms trained with PET/CT features were able to identify some cases of DJD. GLM outperformed the other classification algorithms. Using PET and CT information together was shown to be superior to using PET or CT features alone. Research supported by the Prostate

  5. Photovoltaic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel

    2011-03-01

    Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.

  6. Virtual electrode design for increasing spatial resolution in retinal prosthesis.

    PubMed

    Loizos, Kyle; Cela, Carlos; Marc, Robert; Lazzi, Gianluca

    2016-06-01

    Retinal prostheses systems are currently used to restore partial vision to patients blinded by degenerative diseases by electrically stimulating surviving retinal cells. To obtain likely maximum resolution, electrode size is minimised, allowing for a large quantity on an array and localised stimulation regions. Besides the small size leading to fabrication difficulties and higher electrochemical charge density, there are challenges associated with the number of drivers needed for a large electrode count as well as the strategies to deliver sufficient power to these drivers wirelessly. In hopes to increase electrode resolution while avoiding these issues, the authors propose a new 'virtual electrode' design to increase locations of likely stimulation. Passive metallisation strategically placed between disk electrodes, combined with alternating surrounding stimuli, channel current into a location between electrodes, producing a virtual stimulation site. A computational study was conducted to optimise the passive metal element geometry, quantify the expected current density output, and simulate retinal ganglion cell activity due to virtual electrode stimulation. Results show that this procedure leads to array geometry that focuses injected current and achieves retinal ganglion cell stimulation in a region beneath the 'virtual electrode,' creating an alternate stimulation site without additional drivers. PMID:27382477

  7. Spatially Patterned Electrical Stimulation to Enhance Resolution of Retinal Prostheses

    PubMed Central

    Hottowy, Paweł; Mathieson, Keith; Gunning, Deborah E.; Dąbrowski, Władysław; Litke, Alan M.; Chichilnisky, E. J.

    2014-01-01

    Retinal prostheses electrically stimulate neurons to produce artificial vision in people blinded by photoreceptor degenerative diseases. The limited spatial resolution of current devices results in indiscriminate stimulation of interleaved cells of different types, precluding veridical reproduction of natural activity patterns in the retinal output. Here we investigate the use of spatial patterns of current injection to increase the spatial resolution of stimulation, using high-density multielectrode recording and stimulation of identified ganglion cells in isolated macaque retina. As previously shown, current passed through a single electrode typically induced a single retinal ganglion cell spike with submillisecond timing precision. Current passed simultaneously through pairs of neighboring electrodes modified the probability of activation relative to injection through a single electrode. This modification could be accurately summarized by a piecewise linear model of current summation, consistent with a simple biophysical model based on multiple sites of activation. The generalizability of the piecewise linear model was tested by using the measured responses to stimulation with two electrodes to predict responses to stimulation with three electrodes. Finally, the model provided an accurate prediction of which among a set of spatial stimulation patterns maximized selective activation of a cell while minimizing activation of a neighboring cell. The results demonstrate that tailored multielectrode stimulation patterns based on a piecewise linear model may be useful in increasing the spatial resolution of retinal prostheses. PMID:24695706

  8. VANISHING RETINAL DETACHMENT

    PubMed Central

    2015-01-01

    Purpose: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. Methods: Retrospective case report. Results: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow-up 8 months later. The workup of alternate etiologies was unrevealing. Conclusion: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised. PMID:26352323

  9. Risk of Retinal Vein Occlusion Following End-Stage Renal Disease

    PubMed Central

    Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Tseng, Sung-Huei; Wang, Jiu-Yao; Jan, Ren-Long

    2016-01-01

    Abstract The aim of the study was to investigate the risk of retinal vein occlusion (RVO) following end-stage renal disease (ESRD). The study was designed as a retrospective, nationwide, matched cohort study. The subjects were ESRD patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 585. The study cohort included 92,774 ESRD patients registered between January 2000 and December 2009 at the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 92,774 patients (case:control = 1:1) selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. The incidence and risk of RVO were compared between the ESRD and control groups. The adjusted hazard ratio (HR) for RVO after adjustment for potential confounders was obtained by Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the RVO cumulative incidence rate. The main outcome measure was the incidence of RVO following ESRD. In total, 904 ESRD patients (0.97%) and 410 controls (0.44%) had RVO (P < 0.0001) during the follow-up period, leading to a significantly elevated risk of RVO in the ESRD patients compared with controls (incidence rate ratio = 3.05, 95% confidence interval = 2.72–3.43). After adjustment for potential confounders including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 3.05 times more likely to develop RVO in the full cohort (adjusted hazard ratio = 3.05, 95% confidence interval = 2.64–3.51). In addition, hypertension patients showed high incidence rate of RVO in the ESRD group compared with controls (incidence rate ratio = 1.71, 95% confidence interval = 1.44–2.03) and maintained significant risk of RVO after adjustment for other confounders in the

  10. Risk of Retinal Vein Occlusion Following End-Stage Renal Disease.

    PubMed

    Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Tseng, Sung-Huei; Wang, Jiu-Yao; Jan, Ren-Long

    2016-04-01

    The aim of the study was to investigate the risk of retinal vein occlusion (RVO) following end-stage renal disease (ESRD). The study was designed as a retrospective, nationwide, matched cohort study. The subjects were ESRD patients identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 585. The study cohort included 92,774 ESRD patients registered between January 2000 and December 2009 at the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 92,774 patients (case:control = 1:1) selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. The incidence and risk of RVO were compared between the ESRD and control groups. The adjusted hazard ratio (HR) for RVO after adjustment for potential confounders was obtained by Cox proportional hazard regression analysis. Kaplan-Meier analysis was used to calculate the RVO cumulative incidence rate. The main outcome measure was the incidence of RVO following ESRD.In total, 904 ESRD patients (0.97%) and 410 controls (0.44%) had RVO (P < 0.0001) during the follow-up period, leading to a significantly elevated risk of RVO in the ESRD patients compared with controls (incidence rate ratio = 3.05, 95% confidence interval = 2.72-3.43). After adjustment for potential confounders including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 3.05 times more likely to develop RVO in the full cohort (adjusted hazard ratio = 3.05, 95% confidence interval = 2.64-3.51). In addition, hypertension patients showed high incidence rate of RVO in the ESRD group compared with controls (incidence rate ratio = 1.71, 95% confidence interval = 1.44-2.03) and maintained significant risk of RVO after adjustment for other confounders in the cohort (adjusted

  11. Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.

    PubMed

    O'Quin, Kelly E; Yoshizawa, Masato; Doshi, Pooja; Jeffery, William R

    2013-01-01

    The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish) and eyeless (cavefish) morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F(2) hybrid progeny. We used next generation sequencing (RAD-seq) and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL) affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax. PMID:23437360

  12. Retinal Nerve Fiber Layer Thinning in Alzheimer's Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson's Disease, and Non-Alzheimer's Dementia.

    PubMed

    Pillai, Jagan A; Bermel, Robert; Bonner-Jackson, Aaron; Rae-Grant, Alexander; Fernandez, Hubert; Bena, James; Jones, Stephen E; Ehlers, Justis P; Leverenz, James B

    2016-08-01

    Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and macular volume (MV) utilizing spectral domain optical coherence tomography (SD-OCT) were compared among patients with Alzheimer's disease (AD) dementia, non-Alzheimer's disease (non-AD) dementia, amnestic mild cognitive impairment (aMCI), Parkinson's disease (PD), and age- and sex-matched controls in a cross-sectional cohort study. A total of 116 participants were diagnosed and evaluated (21 AD, 20 aMCI, 20 non-AD, 20 PD, and 34 controls) after comprehensive neurological, neuropsychology, and magnetic resonance imaging (MRI) volumetric evaluations. Retinal nerve fiber layer thickness, GCL thickness, and MV were measured. Analysis of variance models were used to compare groups on MRI volumetric measures, cognitive test results, and SD-OCT measures. Associations between SD-OCT measures and other measures were performed using mixed-effect models. Spectral domain optical coherence tomography analysis of retinal markers, including RNFL thickness, GCL thickness, and MV, did not differ between amnestic MCI, AD dementia, PD, non-AD, dementia, and age- and sex-matched controls in a well-characterized patient cohort. PMID:26888864

  13. Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity

    PubMed Central

    Tajiguli, Abulikemu; Xu, Mingchu; Fu, Qing; Yiming, Rouzimaimaiti; Wang, Keqing; Li, Yumei; Eblimit, Aiden; Sui, Ruifang; Chen, Rui; Aisa, Haji Akber

    2016-01-01

    Inherited retinal disease (IRD) is a category of genetic disorders affecting retina. Understanding the molecular basis of IRD is vital for clinical and genetic classification of patients. Uyghur people is an isolated ethnic group mainly residing in northwestern China with genetic admixture from Europeans and East Asians. The genetic etiology of IRD in this specific population still remains unknown. Here, by next-generation sequencing (NGS), we screened mutations in over 200 known retinal disease genes in a cohort of 12 unrelated Uyghur IRD probands. Out of the 12 probands, six are solved with high confidence, two with low confidence, while the remaining four are unsolved. We identified known disease-causing alleles in this cohort that suggest ancient Uyghur migration and also discovered eight novel disease-associated variants. Our results showed NGS-based mutation screening as a reliable approach for molecular diagnosis. In addition, this approach can also be applied to reveal the genetic history of a specific ethnic group. PMID:26856745

  14. Arterial Stiffness Is Associated With Cardiovascular, Renal, Retinal, and Autonomic Disease in Type 1 Diabetes

    PubMed Central

    Theilade, Simone; Lajer, Maria; Persson, Frederik; Joergensen, Christel; Rossing, Peter

    2013-01-01

    (cardiovascular, renal, retinal, and autonomic disease) independently of other risk factors. PMID:23193205

  15. Clinical and multimodal imaging characteristics of acute Vogt-Koyanagi-Harada disease unassociated with clinically evident exudative retinal detachment.

    PubMed

    Attia, Sonia; Khochtali, Sana; Kahloun, Rim; Ammous, Dhiaeddine; Jelliti, Bechir; Ben Yahia, Salim; Zaouali, Sonia; Khairallah, Moncef

    2016-02-01

    The purpose of this study was to describe the clinical and multimodal imaging findings in acute Vogt-Koyanagi-Harada (VKH) disease without clinically evident exudative retinal detachment (ERD). We retrospectively reviewed the charts of 18 patients (36 eyes), diagnosed with acute VKH disease without clinically evident ERD. All patients underwent complete ophthalmic examination, fundus photography, optical coherence tomography (OCT), B-scan ultrasonography, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Of 18 patients, twelve (66.7 %) were female and 6 (33.3 %) were male. Mean age was 39 years (range, 23-60). Ten patients had been referred with an erroneous diagnosis of primary optic nerve disorder (8; 44.4 %) or isolated anterior uveitis (2; 11.1 %). Anterior chamber or vitreous inflammatory reaction was noted in 22 eyes (61.1 %), each. Fundus findings included optic disc swelling in 30 eyes (83.3 %), retinal striae in 20 eyes (55.5 %), and yellowish deep lesions in 3 eyes (8.3 %). OCT showed a shallow, localized subclinical ERD in 18 eyes (50 %), and retinal pigment epithelial folds in 23 eyes (63.9 %). B-scan ultrasonography showed diffuse, low- to medium-reflective choroidal thickening in all eyes. FA disclosed delayed choroidal perfusion in at least one eye of all patients (100 %), mild pinpoint leakage in 21 eyes (58.3 %), optic disc hyperfluorescence in 35 eyes (97.2 %) and choroidal folds in 13 eyes (36.1 %). ICGA findings included delayed choroidal perfusion in 24 eyes (66.7 %), decrease in the number of large choroidal vessels in 36 eyes (100 %), fuzzy choroidal vessels in 35 eyes (97.2 %), and hypofluorescent dark dots in 28 eyes (77.8 %). The association of bilateral optic disc edema with retinal striae and intraocular inflammatory reaction highly suggests acute VKH disease. A multimodal imaging approach including fundus photography, OCT, B-scan ultrasonography, FA, and ICGA provides important clues for the definite diagnosis and

  16. Homozygosity Mapping and Targeted Sanger Sequencing Reveal Genetic Defects Underlying Inherited Retinal Disease in Families from Pakistan

    PubMed Central

    Waheed, Nadia Khalida; Siddiqui, Sorath Noorani; Mustafa, Bilal; Ayub, Humaira; Ali, Liaqat; Ahmad, Shakeel; Micheal, Shazia; Hussain, Alamdar; Shah, Syed Tahir Abbas; Ali, Syeda Hafiza Benish; Ahmed, Waqas; Khan, Yar Muhammad; den Hollander, Anneke I.; Haer-Wigman, Lonneke; Collin, Rob W. J.; Khan, Muhammad Imran; Qamar, Raheel; Cremers, Frans P. M.

    2015-01-01

    Background Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD). Methods We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families. Results Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. Conclusions Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future. PMID:25775262

  17. Varus deformity of the left lower extremity causing degenerative lesion of the posterior horn of the left medial meniscus in a patient with Paget’s disease of bone

    PubMed Central

    Al Kaissi, Ali; Ganger, Rudolf; Mindler, Gabriel; Klaushofer, Klaus; Grill, Franz

    2014-01-01

    We report on a 42-year-old woman who presented with persistent pain in her left knee with no history of trauma. Sagittal T1-weighted MRI of the left knee showed discontinuity between the anterior and posterior horns of the left medial meniscus, causing effectively the development of degenerative lesion of the posterior horn. The latter was correlated to varus deformity of the left lower extremity associated with subsequent narrowing of the medial knee joint. The unusual craniofacial contour of the patient, the skeletal survey and the elevated serum alkaline phosphatase were compatible with the diagnosis of Paget’s disease of the bone. To alleviate the adverse effect of the mal-alignment of the left femur onto the left knee, corrective osteotomy of the left femoral diaphysis by means of fixators was performed. To the best of our knowledge this is the first clinical report describing the management and the pathological correlation of a unilateral varus deformity of the femoral shaft and degenerative lesions of the left knee in a patient with Paget’s disease of the bone. PMID:25276115

  18. Stage-specific differentiation of iPSCs toward retinal ganglion cell lineage

    PubMed Central

    Deng, Fei; Chen, Mengfei; Liu, Ying; Hu, Huiling; Xiong, Yunfan; Xu, Chaochao; Liu, Yuchun; Li, Kangjun; Zhuang, Jing

    2016-01-01

    Purpose As an alternative and desirable approach for regenerative medicine, human induced pluripotent stem cell (hiPSC) technology raises the possibility of developing patient-tailored cell therapies to treat intractable degenerative diseases in the future. This study was undertaken to guide human Tenon’s capsule fibroblasts-derived iPSCs (TiPSCs) to differentiate along the retinal ganglion cell (RGC) lineage, aiming at producing appropriate cellular material for RGC regeneration. Methods By mimicking RGC genesis, we deliberately administered the whole differentiation process and directed the stage-specific differentiation of human TiPSCs toward an RGC fate via manipulation of the retinal inducers (DKK1+Noggin+Lefty A) alongside master gene (Atoh7) sequentially. Throughout this stepwise differentiation process, changes in primitive neuroectodermal, eye field, and RGC marker expression were monitored with quantitative real-time PCR (qRT-PCR), immunocytochemistry, and/or flow cytometry. Results Upon retinal differentiation, a large fraction of the cells developed characteristics of retinal progenitor cells (RPCs) in response to simulated environment signaling (DKK1+Noggin+Lefty A), which was selectively recovered with manual isolation approaches and then maintained in the presence of mitogen for multiple passages. Thereafter, overexpression of ATOH7 further promoted RGC specification in TiPSC-derived RPCs. A subset of transfected cells displayed RGC-specific expression patterns, including Brn3b, iSlet1, calretinin, and Tuj, and approximately 23% of Brn3b-positive RGC-like cells were obtained finally. Conclusions Our DKK1+Noggin+Lefty A/Atoh7-based RGC-induction regime could efficiently direct TiPSCs to differentiate along RGC lineage in a stage-specific manner, which may provide a benefit to develop possible cell therapies to treat retinal degenerative diseases such as glaucoma. PMID:27293372

  19. Degenerative myelopathy in two Boxer dogs.

    PubMed

    Miller, A D; Barber, R; Porter, B F; Peters, R M; Kent, M; Platt, S R; Schatzberg, S J

    2009-07-01

    Degenerative myelopathy (DM) is a common, slowly progressive, debilitating disease reported in several dog breeds, including the German Shepherd Dog and Pembroke Welsh Corgi. Boxer dogs present occasionally for a thoracolumbar myelopathy for which no cause is identified on MRI or cerebrospinal fluid analysis. Despite a lack of a histologic description of DM in the Boxer in the veterinary literature, such dogs are presumed to have DM. Here we report 2 histologically confirmed cases of DM in the Boxer breed in which histologic studies disclosed marked degenerative changes in the spinal cord that were most prominent in the thoracic and cranial lumbar segments. Lesions consisted of myelin vacuolation and degeneration, myelophagocytosis, reactive astrocytosis, and ellipsoid formation most prominent in the lateral and ventral funiculi. We present a detailed histologic description of DM in the Boxer dog and compare it to DM in other purebred dogs. PMID:19276068

  20. Acetylation: A Lysine Modification with Neuroprotective Effects in Ischemic Retinal Degeneration

    PubMed Central

    Alsarraf, Oday; Fan, Jie; Dahrouj, Mohammad; Chou, C. James; Menick, Donald R.; Crosson, Craig E.

    2014-01-01

    Purpose Neuroretinal ischemic injury contributes to several degenerative diseases in the eye and the resulting pathogenic processes involving a series of necrotic and apoptotic events. This study investigates the time and extent of changes in acetylation, and whether this influences function and survival of neuroretinal cells following injury. Methods Studies evaluated the time course of changes in histone deacetylase (HDAC) activity, histone-H3 acetylation and caspase-3 activation levels as well as retinal morphology and function (electroretinography) following ischemia. In addition, the effect of two HDAC inhibitors, trichostatin-A and valproic acid were also investigated. Results In normal eyes, retinal ischemia produced a significant increase in HDAC activity within 2 hours that was followed by a corresponding significant decrease in protein acetylation by 4 hours. Activated caspase-3 levels were significantly elevated by 24 hours. Treatment with HDAC inhibitors blocked the early decrease in protein acetylation and activation of caspase-3. Retinal immunohistochemistry demonstrated that systemic administration of trichostatin-A or valproic acid, resulted in hyperacetylation of all retinal layers after systemic treatment. In addition, HDAC inhibitors provided a significant functional and structural neuroprtection at seven days following injury relative to vehicle-treated eyes. Conclusions These results provide evidence that increases in HDAC activity is an early event following retinal ischemia, and are accompanied by corresponding decreases in acetylation in advance of caspase-3 activation. In addition to preserving acetylation status, the administration of HDAC inhibitors suppressed caspase activation and provided structural and functional neuroprotection in model of ischemic retinal injury. Taken together these data provide evidence that decrease in retinal acetylation status is a central event in ischemic retinal injury, and the hyperacetylation induced by

  1. Acetylation: a lysine modification with neuroprotective effects in ischemic retinal degeneration.

    PubMed

    Alsarraf, Oday; Fan, Jie; Dahrouj, Mohammad; Chou, C James; Menick, Donald R; Crosson, Craig E

    2014-10-01

    Neuroretinal ischemic injury contributes to several degenerative diseases in the eye and the resulting pathogenic processes involving a series of necrotic and apoptotic events. This study investigates the time and extent of changes in acetylation, and whether this influences function and survival of neuroretinal cells following injury. Studies evaluated the time course of changes in histone deacetylase (HDAC) activity, histone-H3 acetylation and caspase-3 activation levels as well as retinal morphology and function (electroretinography) following ischemia. In addition, the effect of two HDAC inhibitors, trichostatin-A and valproic acid were also investigated. In normal eyes, retinal ischemia produced a significant increase in HDAC activity within 2 h that was followed by a corresponding significant decrease in protein acetylation by 4 h. Activated caspase-3 levels were significantly elevated by 24 h. Treatment with HDAC inhibitors blocked the early decrease in protein acetylation and activation of caspase-3. Retinal immunohistochemistry demonstrated that systemic administration of trichostatin-A or valproic acid, resulted in hyperacetylation of all retinal layers after systemic treatment. In addition, HDAC inhibitors provided a significant functional and structural neuroprotection at seven days following injury relative to vehicle-treated eyes. These results provide evidence that increases in HDAC activity is an early event following retinal ischemia, and are accompanied by corresponding decreases in acetylation in advance of caspase-3 activation. In addition to preserving acetylation status, the administration of HDAC inhibitors suppressed caspase activation and provided structural and functional neuroprotection in model of ischemic retinal injury. Taken together these data provide evidence that decrease in retinal acetylation status is a central event in ischemic retinal injury, and the hyperacetylation induced by HDAC inhibition can provide acute

  2. Inherited retinal disorders in South Africa and the clinical impact of evolving technologies.

    PubMed

    Roberts, L; Goliath, R; Rebello, G; Bardien, S; September, A V; Bartmann, L; Loubser, F; Greenberg, L J; Ramesar, R S

    2016-01-01

    Retinal degenerative disorders (RDDs) encompass a group of inherited diseases characterised by vision loss. The genetic and clinical complexity poses a challenge in unravelling the molecular genetic aetiology of this group of disorders. Furthermore, the population diversity in South Africa (SA) presents researchers with a particularly complicated task. Rapid advances in the development of cutting-edge technological platforms over the past two decades, however, have assisted in overcoming some of the challenges. The RDD research team has utilised these escalating technologies, which has facilitated a corresponding increase in molecular diagnoses. A biorepository has been established and comprises ~3 200 patient DNA samples archived with many forms of RDD (including retinitis pigmentosa, macular dystrophies, Stargardt disease, Leber congenital amaurosis, Usher syndrome and Bardet Biedl syndrome). A comprehensive review is presented of the SA journey spanning 25 years, into elucidating the molecular genetic basis of various forms of RDD in SA. PMID:27245521

  3. MECHANISMS FOR COUNTERING OXIDATIVE STRESS AND DAMAGE IN RETINAL PIGMENT EPITHELIUM

    PubMed Central

    Plafker, Scott M.; O’Mealey, Gary B.; Szweda, Luke I.

    2013-01-01

    Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked. PMID:22878106

  4. Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson's Disease/Dementia with Lewy Bodies.

    PubMed

    Price, Diana L; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Overk, Cassia; Spencer, Brian; Duong-Polk, Karen X; Bonhaus, Douglas; Lindsey, James; Masliah, Eliezer

    2016-01-01

    Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn. PMID:27389831

  5. Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson’s Disease/Dementia with Lewy Bodies

    PubMed Central

    Price, Diana L.; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Overk, Cassia; Spencer, Brian; Duong-Polk, Karen X.; Bonhaus, Douglas; Lindsey, James; Masliah, Eliezer

    2016-01-01

    Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn. PMID:27389831

  6. Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine.

    PubMed Central

    Berson, E. L.; Schmidt, S. Y.; Rabin, A. R.

    1976-01-01

    Plasma free amino-acids were measured in 41 patients with hereditary chorio-retinal degenerations including 26 with retinitis pigmentosa and five with gyrate atrophy of the choroid, six relatives of patients with gyrate atrophy, and 13 normal subjects. Patients with gyrate atrophy had very increased levels of ornithine and slightly decreased mean lysine values. Most relatives had slightly increased ornithine. Taurine, known to be deficient in the plasma of casein-fed cats with photoreceptor degeneration, was normal in all patients. Amino-acid precursors and metabolites of ornithine and taurine were also normal in the plasma. Although the association of high ornithine and gyrate atrophy appears constant, high levels of ornithine alone do not necessarily lead to this degeneration; one patient with known hyperammonaemia, homocitrullinuria and a tenfold increase in plasma ornithine was found to have a normal fundus appearance and normal electroretinogram. PMID:1268174

  7. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  8. Spectral domain optical coherence tomography for in-vivo three-dimensional retinal imaging of small animals

    NASA Astrophysics Data System (ADS)

    Ruggeri, Marco; Wehbe, Hassan; Jiao, Shuliang; Gregori, Giovanni; Jockovich, Maria E.; Hackam, Abigail; Duan, Yuanli; Puliafito, Carmen A.

    2007-02-01

    The purpose of this study is to demonstrate the application of ultrahigh-resolution Spectral Domain Optical Coherence Tomography (SD-OCT) for non contact in vivo imaging of the retina of small animals and quantitative retinal information extraction using 3D segmentation of the OCT images. An ultrahigh-resolution SD-OCT system was specifically designed for in vivo retinal imaging of small animal. En face fundus image was constructed from the measured OCT data, which enables precise registration of the OCT images on the fundus. 3D segmentation algorithms were developed for the calculation of retinal thickness map. High quality OCT images of the retina of mice (B6/SJLF2 for normal retina, Rho -/- for photoreceptor degeneration and LH BETAT AG for retinoblastoma) and rats (Wistar for normal retina) were acquired, where all the retinal layers can be clearly recognized. The calculated retinal thickness map makes successful quantitative comparison of the retinal thickness distribution between normal and degenerative mouse retina. The capabilities of the OCT system provide a valuable tool for longitudinal studies of small animal models of ocular diseases.

  9. Activation of Bone Marrow-Derived Microglia Promotes Photoreceptor Survival in Inherited Retinal Degeneration

    PubMed Central

    Sasahara, Manabu; Otani, Atsushi; Oishi, Akio; Kojima, Hiroshi; Yodoi, Yuko; Kameda, Takanori; Nakamura, Hajime; Yoshimura, Nagahisa

    2008-01-01

    The role of microglia in neurodegeneration is controversial, although microglial activation in the retina has been shown to provide an early response against infection, injury, ischemia, and degeneration. Here we show that endogenous bone marrow (BM)-derived microglia play a protective role in vascular and neural degeneration in the retinitis pigmentosa model of inherited retinal degeneration. BM-derived cells were recruited to the degenerating retina where they differentiated into microglia and subsequently localized to the degenerating vessels and neurons. Inhibition of stromal-derived factor-1 in the retina reduced the number of BM-derived microglia and accelerated the rate of neurovascular degeneration. Systemic depletion of myeloid progenitors also accelerated the degenerative process. Conversely, activation of BM-derived myeloid progenitors by systemic administration of both granulocyte colony-stimulating factor and erythropoietin resulted in the deceleration of retinal degeneration and the promotion of cone cell survival. These data indicate that BM-derived microglia may play a protective role in retinitis pigmentosa. Functional activation of BM-derived myeloid progenitors by cytokine therapy may provide a novel strategy for the treatment of inherited retinal degeneration and other neurodegenerative diseases, regardless of the underlying genetic defect. PMID:18483210

  10. Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes

    PubMed Central

    Abu-Safieh, Leen; Alrashed, May; Anazi, Shamsa; Alkuraya, Hisham; Khan, Arif O.; Al-Owain, Mohammed; Al-Zahrani, Jawahir; Al-Abdi, Lama; Hashem, Mais; Al-Tarimi, Salwa; Sebai, Mohammed-Adeeb; Shamia, Ahmed; Ray-zack, Mohamed D.; Nassan, Malik; Al-Hassnan, Zuhair N.; Rahbeeni, Zuhair; Waheeb, Saad; Alkharashi, Abdullah; Abboud, Emad; Al-Hazzaa, Selwa A.F.; Alkuraya, Fowzan S.

    2013-01-01

    Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time. PMID:23105016

  11. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    PubMed

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  12. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease

    PubMed Central

    Whiting, Rebecca E.H.; Jensen, Cheryl A.; Pearce, Jacqueline W.; Gillespie, Lauren E.; Bristow, Daniel E.; Katz, Martin L.

    2016-01-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10–11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  13. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  14. A Missense Mutation in HK1 Leads to Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Wang, Feng; Wang, Yandong; Zhang, Bin; Zhao, Li; Lyubasyuk, Vera; Wang, Keqing; Xu, Mingchu; Li, Yumei; Wu, Frances; Wen, Cindy; Bernstein, Paul S.; Lin, Danni; Zhu, Susanna; Wang, Hui; Zhang, Kang; Chen, Rui

    2014-01-01

    Purpose. Retinitis pigmentosa (RP) is a genetically heterogeneous disease with over 60 causative genes known to date. Nevertheless, approximately 40% of RP cases remain genetically unsolved, suggesting that many novel disease-causing genes are yet to be identified. In this study, we aimed to identify the causative mutation for a large autosomal dominant RP (adRP) family with negative results from known retinal disease gene screening. Methods. Linkage analysis followed by whole-exome sequencing was performed. Stringent variant filtering and prioritization was carried out to identify the causative mutation. Results. Linkage analysis identified a minimal disease region of 8 Mb on chromosome 10 with a peak parametric logarithm (base 10) of odds (LOD) score of 3.500. Further whole-exome sequencing identified a heterozygous missense mutation (NM_000188.2:c.2539G>A, p.E847K) in hexokinase 1 (HK1) that segregated with the disease phenotype in the family. Biochemical assays showed that the E847K mutation does not affect hexokinase enzymatic activity or the protein stability, suggesting that the mutation may impact other uncharacterized function or result in a gain of function of HK1. Conclusions. Here, we identified HK1 as a novel causative gene for adRP. This is the first report that associates the glucose metabolic pathway with human retinal degenerative disease, suggesting a potential new disease mechanism. PMID:25316723

  15. Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

    PubMed

    Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

    2015-07-01

    This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

  16. Risk of Retinal Artery Occlusion in Patients With End-Stage Renal Disease: A Retrospective Large-Scale Cohort Study.

    PubMed

    Chang, Yuh-Shin; Weng, Shih-Feng; Chang, Chun; Wang, Jhi-Joung; Tseng, Sung-Huei; Ko, Shun-Yao; Su, Shih-Bin; Huang, Chien-Cheng; Wang, Jiu-Yao; Jan, Ren-Long

    2016-04-01

    There is globally increasing prevalence and incidence in end-stage renal disease (ESRD). These patients are frequently reported to have retinal abnormalities and both diseases share some systemic risk factors. Hence, it is clinically relevant to determine whether ESRD is a predictor of retinal artery occlusion (RAO).To investigate the risk of RAO in ESRD patients.A retrospective, nationwide, matched cohort study. The study included 93,766 ESRD patients recruited between 2000 and 2009 from the Taiwan National Health Insurance Research Database. The same number control group included age- and sex-matched patients without ESRD selected from the Taiwan Longitudinal Health Insurance Database, 2000. Data for each patient were collected from the index date until December 2011.The incidence and risk of RAO were compared between the 2 groups. The hazard ratio (HR) for RAO after adjustment for potential confounders was calculated using Cox proportional hazards regression. Kaplan-Meier analysis was used to calculate the cumulative RAO incidence rate.In total, 237 ESRD patients and 73 controls exhibited RAO during follow-up; thus, the RAO incidence rate in ESRD patients was 4.49 times (95% confidence interval (CI), 3.45-5.83) that in the control patients. After adjustment for potential confounders, including diabetes mellitus, hypertension, hyperlipidemia, congestive heart failure, and coronary artery disease, ESRD patients were 2.78 times (95% CI, 2.02-3.84) more likely to develop RAO in cohort for the total sample. Among patients with hypertension, the RAO incidence rate was significantly higher in the ESRD group, and hypertension significantly increased RAO risk even after adjustment for other confounders in the cohort.ESRD increases the risk of RAO, particularly in ESRD patients with hypertension. Therefore, clinicians should educate ESRD patients about RAO and ensure appropriate blood pressure control. PMID:27057891

  17. Vision from next generation sequencing: Multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease

    PubMed Central

    Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

    2015-01-01

    Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of “gene” itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. PMID:25668385

  18. Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease.

    PubMed

    Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

    2015-05-01

    Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of "gene" itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. PMID:25668385

  19. Galectin-1 suppresses autoimmune retinal disease by promoting concomitant Th2- and T regulatory-mediated anti-inflammatory responses.

    PubMed

    Toscano, Marta A; Commodaro, Alessandra G; Ilarregui, Juan M; Bianco, Germán A; Liberman, Ana; Serra, Horacio M; Hirabayashi, Jun; Rizzo, Luiz V; Rabinovich, Gabriel A

    2006-05-15

    Intraocular inflammatory diseases are a common cause of severe visual impairment and blindness. In this study, we investigated the immunoregulatory role of galectin-1 (Gal-1), an endogenous lectin found at sites of T cell activation and immune privilege, in experimental autoimmune uveitis (EAU), a Th1-mediated model of retinal disease. Treatment with rGal-1 either early or late during the course of interphotoreceptor retinoid-binding protein-induced EAU was sufficient to suppress ocular pathology, inhibit leukocyte infiltration, and counteract pathogenic Th1 cells. Administration of rGal-1 at the early or late phases of EAU ameliorated disease by skewing the uveitogenic response toward nonpathogenic Th2 or T regulatory-mediated anti-inflammatory responses. Consistently, adoptive transfer of CD4(+) regulatory T cells obtained from rGal-1-treated mice prevented the development of active EAU in syngeneic recipients. In addition, increased levels of apoptosis were detected in lymph nodes from mice treated with rGal-1 during the efferent phase of the disease. Our results underscore the ability of Gal-1 to counteract Th1-mediated responses through different, but potentially overlapping anti-inflammatory mechanisms and suggest a possible therapeutic use of this protein for the treatment of human uveitic diseases of autoimmune etiology. PMID:16670344

  20. Classical complement activation and acquired immune response pathways are not essential for retinal degeneration in the rd1 mouse

    PubMed Central

    Rohrer, Bärbel; Demos, Christina; Frigg, Rico; Grimm, Christian

    2007-01-01

    Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate and acquired immune system were found to be differentially regulated in the retina during the degenerative process. In addition to this differential regulation of individual genes, we found that in the rd1 retina a significantly higher number of genes involved in immune-related responses were expressed at any given time during the degenerative period. The peak of immune-related gene expression was at postnatal day 14, coinciding with the peak of photoreceptor apoptosis in the rd1 mouse. We directly tested the potential involvement of acquired and innate immune responses in initiation and progression of photoreceptor degeneration by analyzing double mutant animals. Retinal morphology and photoreceptor apoptosis of rd1 mice on a SCID genetic background (no mature T- and B-cells) or in combination with a RAG-1 (no functional B- and T-cells) or a C1qα (no functional classical complement activation pathway) knockout was followed during the degenerative process using light microscopy or TUNEL staining, respectively. Although complement factor C1qα was highly up-regulated in the rd1 retina concomitantly with the degenerative process, lack of this protein did not protect the rd1 retina. Similarly, retinal degeneration and photoreceptor apoptosis appeared to proceed normally in the rd1 mouse lacking functional B- and T-cells. Our results suggest that both, the classical complement system of innate immunity and a functional acquired immune response are not essential for the degenerative process in the rd1 mouse retina. PMID:17069800

  1. Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

    PubMed

    McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

    2014-09-01

    Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. PMID:24398793

  2. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

    PubMed Central

    Fernández-Sánchez, Laura; Rondón, Netxibeth; Esquiva, Gema; Germain, Francisco; de la Villa, Pedro; Cuenca, Nicolás

    2015-01-01

    Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss. PMID:26379056

  3. Ketocarotenoid circulation, but not retinal carotenoid accumulation, is linked to eye disease status in a wild songbird.

    PubMed

    McGraw, Kevin J; Giraudeau, Mathieu; Hill, Geoffrey E; Toomey, Matthew B; Staley, Molly

    2013-11-15

    Pathogenic or parasitic infections pose numerous physiological challenges to organisms. Carotenoid pigments have often been used as biomarkers of disease state and impact because they integrate multiple aspects of an individual's condition and nutritional and health state. Some diseases are known to influence carotenoid uptake from food (e.g. coccidiosis) and carotenoid use (e.g. as antioxidants/immunostimulants in the body, or for sexually attractive coloration), but there is relatively little information in animals about how different types of carotenoids from different tissue sources may be affected by disease. Here we tracked carotenoid accumulation in two body pools (retina and plasma) as a function of disease state in free-ranging house finches (Haemorhous mexicanus). House finches in eastern North America can contract mycoplasmal conjunctivitis (Mycoplasma gallisepticum, or MG), which can progress from eye swelling to eye closure and death. Previous work showed that systemic immune challenges in house finches lower carotenoid levels in retina, where they act as photoprotectors and visual filters. We assessed carotenoid levels during the molt period, a time of year when finches uniquely metabolize ketocarotenoids (e.g. 3-hydroxy-echinenone) for acquisition of sexually selected red plumage coloration, and found that males infected with MG circulated significantly lower levels of 3-hydroxy-echinenone, but no other plasma carotenoid types, than birds exhibiting no MG symptoms. This result uncovers a key biochemical mechanism for the documented detrimental effect of MG on plumage redness in H. mexicanus. In contrast, we failed to find a relationship between MG infection status and retinal carotenoid concentrations. Thus, we reveal differential effects of an infectious eye disease on carotenoid types and tissue pools in a wild songbird. At least compared to retinal sources (which appear somewhat more temporally stable than other body carotenoid pools, even to

  4. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

    PubMed

    Saad, Leonide; Washington, Ilyas

    2016-01-01

    We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway. PMID:26427432

  5. Identification of Novel and Recurrent Disease-Causing Mutations in Retinal Dystrophies Using Whole Exome Sequencing (WES): Benefits and Limitations

    PubMed Central

    Tiwari, Amit; Lemke, Johannes; Altmueller, Janine; Thiele, Holger; Glaus, Esther; Fleischhauer, Johannes; Nürnberg, Peter

    2016-01-01

    Inherited retinal dystrophies (IRDs) are Mendelian diseases with tremendous genetic and phenotypic heterogeneity. Identification of the underlying genetic basis of these dystrophies is therefore challenging. In this study we employed whole exome sequencing (WES) in 11 families with IRDs and identified disease-causing variants in 8 of them. Sequence analysis of about 250 IRD-associated genes revealed 3 previously reported disease-associated variants in RHO, BEST1 and RP1. We further identified 5 novel pathogenic variants in RPGRIP1 (p.Ser964Profs*37), PRPF8 (p.Tyr2334Leufs*51), CDHR1 (p.Pro133Arg and c.439-17G>A) and PRPF31 (p.Glu183_Met193dup). In addition to confirming the power of WES in genetic diagnosis of IRDs, we document challenges in data analysis and show cases where the underlying genetic causes of IRDs were missed by WES and required additional techniques. For example, the mutation c.439-17G>A in CDHR1 would be rated unlikely applying the standard WES analysis. Only transcript analysis in patient fibroblasts confirmed the pathogenic nature of this variant that affected splicing of CDHR1 by activating a cryptic splice-acceptor site. In another example, a 33-base pair duplication in PRPF31 missed by WES could be identified only via targeted analysis by Sanger sequencing. We discuss the advantages and challenges of using WES to identify mutations in heterogeneous diseases like IRDs. PMID:27391102

  6. Identification of Novel and Recurrent Disease-Causing Mutations in Retinal Dystrophies Using Whole Exome Sequencing (WES): Benefits and Limitations.

    PubMed

    Tiwari, Amit; Lemke, Johannes; Altmueller, Janine; Thiele, Holger; Glaus, Esther; Fleischhauer, Johannes; Nürnberg, Peter; Neidhardt, John; Berger, Wolfgang

    2016-01-01

    Inherited retinal dystrophies (IRDs) are Mendelian diseases with tremendous genetic and phenotypic heterogeneity. Identification of the underlying genetic basis of these dystrophies is therefore challenging. In this study we employed whole exome sequencing (WES) in 11 families with IRDs and identified disease-causing variants in 8 of them. Sequence analysis of about 250 IRD-associated genes revealed 3 previously reported disease-associated variants in RHO, BEST1 and RP1. We further identified 5 novel pathogenic variants in RPGRIP1 (p.Ser964Profs*37), PRPF8 (p.Tyr2334Leufs*51), CDHR1 (p.Pro133Arg and c.439-17G>A) and PRPF31 (p.Glu183_Met193dup). In addition to confirming the power of WES in genetic diagnosis of IRDs, we document challenges in data analysis and show cases where the underlying genetic causes of IRDs were missed by WES and required additional techniques. For example, the mutation c.439-17G>A in CDHR1 would be rated unlikely applying the standard WES analysis. Only transcript analysis in patient fibroblasts confirmed the pathogenic nature of this variant that affected splicing of CDHR1 by activating a cryptic splice-acceptor site. In another example, a 33-base pair duplication in PRPF31 missed by WES could be identified only via targeted analysis by Sanger sequencing. We discuss the advantages and challenges of using WES to identify mutations in heterogeneous diseases like IRDs. PMID:27391102

  7. The degenerative spine: pattern recognition and guidelines to image interpretation.

    PubMed

    Parizel, P M; Van Hoyweghen, A J L; Bali, A; Van Goethem, J; Van Den Hauwe, L

    2016-01-01

    Degenerative disease of the spine, in the form of intervertebral disc degeneration and bony growth, causing osteophytes and impinging upon the spinal canal and neural foramina, is the most frequent disorder affecting the spine. In this chapter we first discuss briefly the indications for computed tomography or magnetic resonance imaging in suspected degenerative spine disease. We then describe changes of disc height, signal intensity, and disc contour with aging and repeated microtrauma, as well as the imaging techniques most appropriate to image them. A grading system for lumbar disc changes is provided. Stenosis of the canal and neural foramina is reviewed next, concluding with a description of degenerative changes affecting the vertebral endplates and bone marrow. PMID:27430442

  8. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    PubMed

    Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

    2016-06-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. PMID:27245308

  9. Early results and review of the literature of a novel hybrid surgical technique combining cervical arthrodesis and disc arthroplasty for treating multilevel degenerative disc disease: opposite or complementary techniques?

    PubMed Central

    Assietti, Roberto; Corbino, Leonardo; Olindo, Giuseppe; Foti, Pietro V.; Russo, Vittorio; Albanese, Vincenzo

    2009-01-01

    We report the clinical and radiological results on the safety and efficacy of an unusual surgical strategy coupling anterior cervical discectomy and fusion and total disc replacement in a single-stage procedure, in patients with symptomatic, multilevel cervical degenerative disc disease (DDD). The proposed hybrid, single-stage, fusion–nonfusion technique aims either at restoring or maintaining motion where appropriate or favouring bony fusion when indicated by degenerative changes. Twenty-four patients (mean age 46.7 years) with symptomatic, multilevel DDD, either soft disc hernia or different stage spondylosis per single level, with predominant anterior myeloradicular compression and absence of severe alterations of cervical spine sagittal alignment, have been operated using such hybrid technique. Fifteen patients underwent a two-level surgery, seven patients received a three-level surgery and two a four-level procedure, for a total of 59 implanted devices (27 disc prostheses and 32 cages). Follow-up ranged between 12 and 40 months (mean 23.8 months). In all but one patient clinical follow-up (neurological examination, Nurick scale, NDI, SF-36) demonstrated significant improvement; radiological evaluation showed functioning disc prostheses (total range of motion 3–15°) and fusion through cages. None of the patients needed revision surgery for persisting or recurring symptoms, procedure-related complications or devices dislocations. To the authors’ best knowledge, this is the first study with the longest available follow-up describing a different concept in the management of cervical multilevel DDD. Although larger series with longer follow-up are needed, in selected cases of symptomatic multilevel DDD, the proposed surgical strategy appears to be a safe and reliable application of combined arthroplasty and arthrodesis during a single surgical procedure. PMID:19415346

  10. Expression pattern in retinal photoreceptors of POMGnT1, a protein involved in muscle-eye-brain disease

    PubMed Central

    Uribe, Mary Luz; Haro, Carmen; Campello, Laura; Cruces, Jesús; Martín-Nieto, José

    2016-01-01

    Purpose The POMGNT1 gene, encoding protein O-linked-mannose β-1,2-N-acetylglucosaminyltransferase 1, is associated with muscle-eye-brain disease (MEB) and other dystroglycanopathies. This gene’s lack of function or expression causes hypoglycosylation of α-dystroglycan (α-DG) in the muscle and the central nervous system, including the brain and the retina. The ocular symptoms of patients with MEB include retinal degeneration and detachment, glaucoma, and abnormal electroretinogram. Nevertheless, the POMGnT1 expression pattern in the healthy mammalian retina has not yet been investigated. In this work, we address the expression of the POMGNT1 gene in the healthy retina of a variety of mammals and characterize the distribution pattern of this gene in the adult mouse retina and the 661W photoreceptor cell line. Methods Using reverse transcription (RT)–PCR and immunoblotting, we studied POMGNT1 expression at the mRNA and protein levels in various mammalian species, from rodents to humans. Immunofluorescence confocal microscopy analyses were performed to characterize the distribution profile of its protein product in mouse retinal sections and in 661W cultured cells. The intranuclear distribution of POMT1 and POMT2, the two enzymes preceding POMGnT1 in the α-DG O-mannosyl glycosylation pathway, was also analyzed. Results POMGNT1 mRNA and its encoded protein were expressed in the neural retina of all mammals studied. POMGnT1 was located in the cytoplasmic fraction in the mouse retina and concentrated in the myoid portion of the photoreceptor inner segments, where the protein colocalized with GM130, a Golgi complex marker. The presence of POMGnT1 in the Golgi complex was also evident in 661W cells. However, and in contrast to retinal tissue, POMGnT1 additionally accumulated in the nucleus of the 661W photoreceptors. Colocalization was found within this organelle between POMGnT1 and POMT1/2, the latter associated with euchromatic regions of the nucleus. Conclusions

  11. Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis

    NASA Astrophysics Data System (ADS)

    Inayat, Samsoon; Rountree, Corey M.; Troy, John B.; Saggere, Laxman

    2015-02-01

    Objective. No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ˜ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter

  12. [Neuropathologic markers in degenerative dementias].

    PubMed

    Hauw, J J; Seilhean, D; Colle, M A; Hogenhuys, J; Duyckaerts, C

    1998-01-01

    The number of neuropathological markers used for the diagnosis of degenerative dementias is rapidly increasing, and this is somewhat confusing: some lesions described a long time ago, such as ballooned cells, proved to be less specific than they were supposed to be; this is also the case for Lewy bodies, that have been recognised in a larger spectrum of disorders than thought a few years ago. On the contrary, for an increasing number of neuropathologists, Pick bodies are now mandatory for the diagnosis of Pick disease, and this contrasts with the prevalent opinions of the late sixties or seventies. There are a number of reasons for the changing significance of neuropathological markers. Three of them can be easily identified: 1) the burst of immunohistochemistry into neuropathology allowed an easier recognition, a better delineation and new pathophysiological approaches to old lesions, and a dramatic increase in the description of new markers, especially in glial cells; 2) in some conditions characterized by the number and distribution of some lesions rather than by their mere presence, such as aging and Alzheimer disease, a better neuroanatomical point of view permitted new insights into the concept of disease versus age-related changes; 3) more accurate clinicopathologic correlations showed clearly the need of grouping or lumping together some entities: for example, obvious relationship aroused between progressive supranuclear palsy and corticobasal degeneration; in contrast, distinguishing different disorders in the frontal lobe dementias grouped together into "Pick disease" was felt necessary. This review summarizes the main criteria for identification, and the presumed meaning of the chief markers indicating the presence of abnormally phosphorylated tau proteins, A beta peptides, and PrP proteins. Abnormally phosphorylated tau proteins can be stored in the neurons, and participate in the constitution of many lesions (neurofibrillary tangles, neuropil threads

  13. Association Between Alzheimer's Disease and Glaucoma: A Study Based on Heidelberg Retinal Tomography and Frequency Doubling Technology Perimetry

    PubMed Central

    Cesareo, Massimo; Martucci, Alessio; Ciuffoletti, Elena; Mancino, Raffaele; Cerulli, Angelica; Sorge, Roberto P.; Martorana, Alessandro; Sancesario, Giuseppe; Nucci, Carlo

    2015-01-01

    Aim: To assess the frequency of glaucoma-like alterations in Alzheimer's disease (AD) patients using Heidelberg Retinal Tomograph III (HRT-3) and Frequency Doubling Technology (FDT) perimetry. Methods: The study included 51 eyes of 51 AD subjects and 67 eyes of 67 age- and sex-matched controls. Subjects underwent an ophthalmological examination including measurements of intraocular pressure (IOP), Matrix FDT visual field testing, optic nerve head morphology and retinal nerve fiber layer thickness (RNFLt) assessment by slit-lamp biomicroscopy and HRT-3. Results: The frequency of alterations was significantly higher in the AD group (27.5 vs. 7.5%; p = 0.003; OR = 4.69). AD patients showed lower IOP (p = 0.000) despite not significantly different values of central corneal thickness (CCT) between the groups (p = 0.336). Of all the stereometric parameters measured by HRT-3, RNFLt was significantly lower in AD patients (p = 0.013). This group also had significantly worse results in terms of Moorfields Regression Analysis (p = 0.027). Matrix showed significantly worse Mean Deviation (MD) (p = 0.000) and Pattern Standard Deviation (PSD) (p = 0.000) values and more altered Glaucoma Hemifield Test (p = 0.006) in AD patients. Pearson's R correlation test showed that Mini Mental State Examination is directly correlated with MD (R = 0.349; p = 0.034) and inversely correlated with PSD (R = −0.357; p = 0.030). Conclusion: Patients with AD have a higher frequency of glaucoma-like alterations, as detected by the use of HRT-3. These alterations were not associated with elevated IOP or abnormal CCT values. PMID:26733792

  14. Line Bisection in Parkinson’s Disease: Investigation of Contributions of Visual Field, Retinal Vision, and Scanning Patterns to Visuospatial Function

    PubMed Central

    Laudate, Thomas M.; Neargarder, Sandy; Cronin-Golomb, Alice

    2013-01-01

    Parkinson’s disease (PD) is characterized by disorders of visuospatial function that can impact everyday functioning. Visuospatial difficulties are more prominent in those whose motor symptoms begin on the left body side (LPD) than the right body side (RPD) and have mainly been attributed to parietal dysfunction. The source of visuospatial dysfunction is unclear, as in addition to subcortical–cortical changes, there are irregularities of visual scanning and potentially of retinal-level vision in PD. To assess these potential contributors, performance on a visuospatial task—line bisection—was examined together with retinal structure (nerve fiber layer thickness, measured by optical coherence tomography [OCT]), retinal function (contrast sensitivity, measured by frequency-doubling technology [FDT]), and visual scanning patterns. Participants included 20 nondemented patients (10 LPD, 10 RPD) and 11 normal control (NC) adults. Relative to the other groups, LPD were expected to show rightward bias on horizontal line bisection, especially within the left visual hemispace, and downward bias on vertical bisection. LPD relative rightward bias was confirmed, though not mainly within the left hemispace and not correlated with retinal structure or function. Retinal thinning was seen in LPD relative to RPD. Qualitative visualization of eye movements suggested greater LPD exploration of the right than left side of the line during horizontal bisection, and some overall compression of scanning range in RPD (both orientations) and LPD (primarily vertical). Results indicated that rightward visuospatial bias in our LPD sample arose not from abnormalities at the retinal level but potentially from attentional biases, reflected in eye movement patterns. PMID:23356329

  15. Bifurcation analysis of a photoreceptor interaction model for Retinitis Pigmentosa

    NASA Astrophysics Data System (ADS)

    Camacho, Erika T.; Radulescu, Anca; Wirkus, Stephen

    2016-09-01

    Retinitis Pigmentosa (RP) is the term used to describe a diverse set of degenerative eye diseases affecting the photoreceptors (rods and cones) in the retina. This work builds on an existing mathematical model of RP that focused on the interaction of the rods and cones. We non-dimensionalize the model and examine the stability of the equilibria. We then numerically investigate other stable modes that are present in the system for various parameter values and relate these modes to the original problem. Our results show that stable modes exist for a wider range of parameter values than the stability of the equilibrium solutions alone, suggesting that additional approaches to preventing cone death may exist.

  16. Association between a relative afferent pupillary defect using pupillography and inner retinal atrophy in optic nerve disease

    PubMed Central

    Takizawa, Go; Miki, Atsushi; Maeda, Fumiatsu; Goto, Katsutoshi; Araki, Syunsuke; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

    2015-01-01

    Purpose The aim of this study was to compare the asymmetrical light reflex of the control subjects and patients with optic nerve disease and to evaluate the relationships among the relative afferent pupillary defect (RAPD), visual acuity (VA), central critical fusion frequency (CFF), ganglion cell complex thickness (GCCT), and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using spectral-domain optical coherence tomography. Materials and methods Using a pupillography device, the RAPD scores from 15 patients with unilateral optic nerve disease and 35 control subjects were compared. The diagnostic accuracy of the RAPD amplitude and latency scores was compared using the area under the receiver operating characteristic curve. Thereafter, we assessed the relationships among the RAPD scores, VA, central CFF, GCCT, and cpRNFLT. Results The average RAPD amplitude score in patients with optic nerve disease was significantly higher than that of the control subjects (P<0.001). The average RAPD latency score in patients with optic nerve disease was significantly higher than that of the control subjects (P=0.001). The area under the receiver operating characteristic curve for the RAPD amplitude score was significantly higher than that for the latency score (P=0.010). The correlation coefficients for the RAPD amplitude and latency scores were 0.847 (P<0.001) and 0.874 (P<0.001) for VA, −0.868 (P<0.001) and −0.896 (P<0.001) for central CFF, −0.593 (P=0.020) and −0.540 (P=0.038) for GCCT, and −0.267 (P=0.337) and −0.228 (P=0.413) for cpRNFLT, respectively. Conclusion Our results suggest that pupillography is useful for detecting optic nerve disease. PMID:26487800

  17. Retinal Imaging and Image Analysis

    PubMed Central

    Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

    2011-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:21743764

  18. Quantitative analysis of retinal OCT.

    PubMed

    Sonka, Milan; Abràmoff, Michael D

    2016-10-01

    Clinical acceptance of 3-D OCT retinal imaging brought rapid development of quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well as facilitated new research in retinal diseases. One of the cornerstones of many such analyses is segmentation and thickness quantification of retinal layers and the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation approach being extremely well suited for the task. Once retinal layers are segmented, regional thickness, brightness, or texture-based indices of individual layers can be easily determined and thus contribute to our understanding of retinal or optic nerve head (ONH) disease processes and can be employed for determination of disease status, treatment responses, visual function, etc. Out of many applications, examples provided in this paper focus on image-guided therapy and outcome prediction in age-related macular degeneration and on assessing visual function from retinal layer structure in glaucoma. PMID:27503080

  19. Does 360° lumbar spinal fusion improve long-term clinical outcomes after failure of conservative treatment in patients with functionally disabling single-level degenerative lumbar disc disease? Results of 5-year follow-up in 75 postoperative patients

    PubMed Central

    Zigler, Jack E.; Delamarter, Rick B.

    2013-01-01

    Background Surgical treatment of patients with mechanical degenerative disc disease has been controversial, but improvements in clinical outcomes have been shown in properly selected patients with disease-specific diagnoses, with fusion arguably now becoming the “gold standard” for surgical management of these patients. No published study thus far has been designed for prospective enrollment of patients with specific inclusion/exclusion criteria in whom at least 6 months of conservative therapy has failed and who are then offered a standardized surgical procedure and are followed up for 5 years. Methods The study group was composed of the patients in the prospective, randomized Food and Drug Administration Investigational Device Exemption trial comparing ProDisc-L (Synthes Spine, West Chester, Pennsylvania) with 360° fusion for the treatment of single-level symptomatic disc degeneration. Of 80 patients randomized to 360° fusion after failure of non-operative care, 75 were treated on protocol with single-level fusions. Follow-up of this treatment cohort was 97% at 2 years and 75% at 5 years and serves as the basis for this report. Patients in the trial were required to have failure of at least 6 months of nonoperative care and in fact had failure of an average of 9 months of nonoperative treatment. The mean Oswestry Disability Index score indicated greater than 60% impairment. The mean entry-level pain score on a visual analog scale was greater than 8 of 10. Results After fusion, not only did patients have significant improvements in measurable clinical outcomes such as the Oswestry Disability Index score and pain score on a visual analog scale but there were also substantial improvements in their functional status and quality of life. Specifically, over 80% of patients in this study had improvements in recreational status that was maintained 5 years after index surgery, indicating substantial improvements in life quality that were not afforded by months of

  20. Copper deficiency myelopathy in the setting of advanced degenerative cervical spondylosis.

    PubMed

    Page, Paul S; Nazar, Ryan G; Park, Michael C; James, Robert F

    2016-08-01

    When presenting conjointly, degenerative cervical spondylosis and copper deficiency myelopathy may be difficult to differentiate providing the potential for mismanagement and unnecessary surgery. We present a case of a 69-year-old female with copper deficiency myelopathy secondary to previous bowel resection in the setting of advanced degenerative cervical spondylotic disease. PMID:26337459

  1. Transcriptome analysis and molecular signature of human retinal pigment epithelium

    PubMed Central

    Strunnikova, N.V.; Maminishkis, A.; Barb, J.J.; Wang, F.; Zhi, C.; Sergeev, Y.; Chen, W.; Edwards, A.O.; Stambolian, D.; Abecasis, G.; Swaroop, A.; Munson, P.J.; Miller, S.S.

    2010-01-01

    Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed ‘signature’ genes by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 RPE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of RPE signature genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the RPE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that RPE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The RPE signature gene set should allow the validation of RPE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases. PMID:20360305

  2. Evaluation of the arrestin gene in patients with retinitis pigmentosa or an allied disease

    SciTech Connect

    DeStefano, D.J.; Berson, E.L.; Dryja, T.P.

    1994-09-01

    Arrestin, also called 48K protein or S-antigen, plays a role in deactivating rhodopsin, the photosensitive, seven-helix, G-protein receptor found in rod photoreceptors. In Drosophila, null mutations in arrestin genes cause a light-dependent photoreceptor degeneration. It is possible that a comparable photoreceptor degeneration in humans is caused by defects in the rod arrestin gene. In order to evaluate this possibility, we are characterizing the human arrestin locus on chromosome 2q. We screened a genomic library (5 million plaques) using an arrestin cDNA clone. Sixty-eight hybridizing clones were identified; portions of 7 clones were sequenced to determine the intron sequence flanking the exons. We are using SSCP analysis and direct genomic sequencing to screen the entire coding region, splice donor and acceptor sites, and the promoter region of the arrestin gene in 188 patients with autosomal dominant and 104 patients with autosomal recessive retinitis pigmentosa. We have already obtained flanking intron sequences necessary for SSCP analysis for 13 of 16 exons. So far, we have identified 4 silent base changes at codons 67 (TGC-to-TGT), 107 (CTG-to-CTC), 163 (GCC-to-GCT), and 288 (CTG-to-TGT), all with allele frequencies at 1% or less. Several other variant bands detected by SSCP analysis are currently being sequenced.

  3. Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies

    PubMed Central

    Beryozkin, Avigail; Shevah, Elia; Kimchi, Adva; Mizrahi-Meissonnier, Liliana; Khateb, Samer; Ratnapriya, Rinki; Lazar, Csilla H.; Blumenfeld, Anat; Ben-Yosef, Tamar; Hemo, Yitzhak; Pe’er, Jacob; Averbuch, Eduard; Sagi, Michal; Boleda, Alexis; Gieser, Linn; Zlotogorski, Abraham; Falik-Zaccai, Tzipora; Alimi-Kasem, Ola; Jacobson, Samuel G.; Chowers, Itay; Swaroop, Anand; Banin, Eyal; Sharon, Dror

    2015-01-01

    Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed. Sanger sequencing was used to validate potential pathogenic variants that were also subjected to segregation analysis in families. Thirty-three causative mutations (19 novel and 14 known) in 25 genes were identified in 33 of the 68 families. The vast majority of mutations (30 out of 33) have not been reported in the Israeli and the Palestinian populations. Nine out of the 33 mutations were detected in additional families from the same ethnic population, suggesting a founder effect. In two families, identified phenotypes were different from the previously reported clinical findings associated with the causative gene. This is the largest genetic analysis of IRDs in the Israeli and Palestinian populations to date. We also demonstrate that WES is a powerful tool for rapid analysis of known disease genes in large patient cohorts. PMID:26306921

  4. [Intrinsically Photosensitive Retinal Ganglion Cells].

    PubMed

    Skorkovská, K; Skorkovská, Š

    2015-06-01

    Recently discovered intrinsically photosensitive melanopsin-containing retinal ganglion cells contribute to circadian photoentrainment and pupillary constriction; recent works have also brought new evidence for their accessory role in the visual system in humans. Pupil light reaction driven by individual photoreceptors can be isolated by means of the so called chromatic pupillography. The use of chromatic stimuli to elicit different pupillary responses may become an objective clinical pupil test in the detection of retinal diseases and in assessing new therapeutic approaches particularly in hereditary retinal degenerations like retinitis pigmentosa. In advanced stages of disease, the pupil light reaction is even more sensitive than standard electroretinography for detecting residual levels of photoreceptor activity. This review summarizes current knowledge on intrinsically photosensitive retinal cells and highlights its possible implications for clinical practice. PMID:26201360

  5. Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model

    PubMed Central

    Hanif, Adam M.; Lawson, Eric C.; Prunty, Megan; Gogniat, Marissa; Aung, Moe H.; Chakraborty, Ranjay; Boatright, Jeffrey H.; Pardue, Machelle T.

    2015-01-01

    Purpose Our previous investigations showed that involuntary treadmill exercise is neuroprotective in a light-induced retinal degeneration mouse model, and it may act through activation of tropomyosin-related kinase B (TrkB) receptors. This study investigated whether voluntary running wheel exercise can be neuroprotective in an inheritable model of the retinal degenerative disease retinitis pigmentosa (RP), rd10 mice. Methods Breeding pairs of rd10 and C57BL/6J mice were given free-spinning (active) or locked (inactive) running wheels. Pups were weaned into separate cages with their parents' respective wheel types, and visual function was tested with ERG and a virtual optokinetic system at 4, 5, and 6 weeks of age. Offspring were killed at 6 weeks of age and retinal cross-sections were prepared for photoreceptor nuclei counting. Additionally, separate cohorts of active and inactive rd10 pups were injected daily for 14 days after eye opening with a selective TrkB receptor antagonist (ANA-12) or vehicle solution and assessed as described above. Results Mice in the rd10 active group exhibited significant preservation of visual acuity, cone nuclei, and total photoreceptor nuclei number. Injection with ANA-12 precluded the preservation of visual acuity and photoreceptor nuclei number in rd10 mice. Conclusions Voluntary running partially protected against the retinal degeneration and vision loss that otherwise occurs in the rd10 mouse model of RP. This protection was prevented by injection of ANA-12, suggesting that TrkB activation mediates exercise's preservation of the retina. Exercise may serve as an effective, clinically translational intervention against retinal degeneration. PMID:26567796

  6. Renal-Retinal Ciliopathy Gene Sdccag8 Regulates DNA Damage Response Signaling

    PubMed Central

    Airik, Rannar; Slaats, Gisela G.; Guo, Zhi; Weiss, Anna-Carina; Khan, Naheed; Ghosh, Amiya; Hurd, Toby W.; Bekker-Jensen, Simon; Schrøder, Jacob M.; Elledge, Steve J.; Andersen, Jens S.; Kispert, Andreas; Castelli, Maddalena; Boletta, Alessandra; Giles, Rachel H.

    2014-01-01

    Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that are frequently associated with extrarenal pathologies such as retinal degeneration, obesity, and intellectual disability. We recently identified mutations in a gene encoding the centrosomal protein SDCCAG8 as causing NPHP type 10 in humans. To study the role of Sdccag8 in disease pathogenesis, we generated a Sdccag8 gene-trap mouse line. Homozygous Sdccag8gt/gt mice lacked the wild-type Sdccag8 transcript and protein, and recapitulated the human phenotypes of NPHP and retinal degeneration. These mice exhibited early onset retinal degeneration that was associated with rhodopsin mislocalization in the photoreceptors and reduced cone cell numbers, and led to progressive loss of vision. By contrast, renal histologic changes occurred later, and no global ciliary defects were observed in the kidneys. Instead, renal pathology was associated with elevated levels of DNA damage response signaling activity. Cell culture studies confirmed the aberrant activation of DNA damage response in Sdccag8gt/gt-derived cells, characterized by elevated levels of γH2AX and phosphorylated ATM and cell cycle profile abnormalities. Our analysis of Sdccag8gt/gt mice indicates that the pleiotropic phenotypes in these mice may arise through multiple tissue-specific disease mechanisms. PMID:24722439

  7. Retinal Prosthesis

    PubMed Central

    Weiland, James D.; Humayun, Mark S.

    2015-01-01

    Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses. PMID:24710817

  8. Foveomacular retinitis.

    PubMed Central

    Kuming, B S

    1986-01-01

    A group of patients is described who developed the clinical features of foveomacular retinitis. No causative factors were isolated, and all patients strongly denied any type of sun gazing. It is possible that there is a group of patients who have the features of foveomacular retinitis but have not had any direct exposure to the sun. These patients would then constitute a primary type of foveomacular retinitis, as opposed to a secondary type which has a known cause and is synonymous with solar retinopathy. Images PMID:3790482

  9. Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front

    PubMed Central

    Cideciyan, Artur V.; Swider, Malgorzata; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

    2015-01-01

    Purpose To evaluate the progression of the earliest stage of disease in ABCA4-associated retinal degenerations (RDs). Methods Near-infrared excited reduced-illuminance autofluorescence imaging was acquired across the retina up to 80 degrees eccentricity in 44 patients with two ABCA4 alleles. The eccentricity of the leading disease front (LDF) corresponding to the earliest stage of disease was measured along the four meridians. A mathematical model describing the expansion of the LDF was developed based on 6 years of longitudinal follow-up. Results The extent of LDF along the superior, inferior, and temporal meridians showed a wide spectrum from 3.5 to 70 degrees. In patients with longitudinal data, the average centrifugal expansion rate was 2 degrees per year. The nasal extent of LDF between the fovea and ONH ranged from 4.3 to 16.5 degrees and expanded at 0.35 degrees per year. The extent of LDF beyond ONH ranged from 19 to 75 degrees and expanded on average at 2 degrees per year. A mathematical model fit well to the longitudinal data describing the expansion of the LDF. Conclusions The eccentricity of the LDF in ABCA4-RD shows a continuum from parafovea to far periphery along all four meridians consistent with a wide spectrum of severity observed clinically. The model of progression may provide a quantitative prediction of the LDF expansion based on the age and eccentricity of the LDF at a baseline visit, and thus contribute significantly to the enrollment of candidates appropriate for clinical trials planning specific interventions, efficacy outcomes, and durations. PMID:26377081

  10. Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer's disease: a meta-analysis

    PubMed Central

    He, Xue-Fei; Liu, Yi-Ting; Peng, Cheng; Zhang, Fan; Zhuang, Shi; Zhang, Jin-Song

    2012-01-01

    AIM To investigate the difference of retinal nerve fiber layer (RNFL) thickness between Alzheimer's disease patients and normal people, so as to provide clue for the early diagnosis of Alzheimer's disease. METHODS The articles on the association of RNFL thickness and Alzheimer's disease were retrieved by searching international and national databases. The qualified articles were assessed by meta analysis with Stata11.0 software. The results were pooled using weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). RESULTS Totally 7 studies enrolled 324 eyes were included in the meta-analysis. The results of meta analysis showed that in AD patients, there was a significant average RNFL thickness reduction compared with the control group [WMD=-17.561, 95%CI: (-23.971, -11.151)]. There were significant differences in superior, inferior, nasal and temporal RNFL thickness between the two groups. WMD with a 95%CI were [-18.829, 95%CI:(-25.915, -11.743); P<0.05], [-25.775, 95%CI:(-34.304, -17.247); P<0.05], [-16.877, 95%CI: (-29.141, -4.613); P<0.001] and [-14.565, 95%CI:(-28.002, -1.128); P<0.001] respectively. Begg's test and Egger's test did not show significant difference, funnel plot was basically symmetrical, indicating that there was no publication bias existed. CONCLUSION There are significant differences in the RNFL thickness in all quadrants between the two groups. RNFL thickness is reduced in AD patients compared with the control group. PMID:22773997

  11. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

    PubMed Central

    Arcinue, Cheryl A.; Bartsch, Dirk-Uwe; El-Emam, Sharif Y.; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R.

    2015-01-01

    Purpose To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Methods Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Results Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Conclusion Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis. PMID:26244973

  12. Pathway to Retinal Oximetry

    PubMed Central

    Beach, James

    2014-01-01

    Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry. PMID:25237591

  13. Mechanism of All-trans-retinal Toxicity with Implications for Stargardt Disease and Age-related Macular Degeneration*

    PubMed Central

    Chen, Yu; Okano, Kiichiro; Maeda, Tadao; Chauhan, Vishal; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

    2012-01-01

    Compromised clearance of all-trans-retinal (atRAL), a component of the retinoid cycle, increases the susceptibility of mouse retina to acute light-induced photoreceptor degeneration. Abca4−/−Rdh8−/− mice featuring defective atRAL clearance were used to examine the one or more underlying molecular mechanisms, because exposure to intense light causes severe photoreceptor degeneration in these animals. Here we report that bright light exposure of Abca4−/−Rdh8−/− mice increased atRAL levels in the retina that induced rapid NADPH oxidase-mediated overproduction of intracellular reactive oxygen species (ROS). Moreover, such ROS generation was inhibited by blocking phospholipase C and inositol 1,4,5-trisphosphate-induced Ca2+ release, indicating that activation occurs upstream of NADPH oxidase-mediated ROS generation. Because multiple upstream G protein-coupled receptors can activate phospholipase C, we then tested the effects of antagonists of serotonin 2A (5-HT2AR) and M3-muscarinic (M3R) receptors and found they both protected Abca4−/−Rdh8−/− mouse retinas from light-induced degeneration. Thus, a cascade of signaling events appears to mediate the toxicity of atRAL in light-induced photoreceptor degeneration of Abca4−/−Rdh8−/− mice. A similar mechanism may be operative in human Stargardt disease and age-related macular degeneration. PMID:22184108

  14. Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders.

    PubMed

    Al-Maawali, Almundher; Dupuis, Lucie; Blaser, Susan; Heon, Elise; Tarnopolsky, Mark; Al-Murshedi, Fathiya; Marshall, Christian R; Paton, Tara; Scherer, Stephen W; Roelofsen, Jeroen; van Kuilenburg, André B P; Mendoza-Londono, Roberto

    2015-03-01

    PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders. PMID:24961627

  15. Perceiving Collision Impacts in Alzheimer’s Disease: The Effect of Retinal Eccentricity on Optic Flow Deficits

    PubMed Central

    Kim, Nam-Gyoon

    2015-01-01

    The present study explored whether the optic flow deficit in Alzheimer’s disease (AD) reported in the literature transfers to different types of optic flow, in particular, one that specifies collision impacts with upcoming surfaces, with a special focus on the effect of retinal eccentricity. Displays simulated observer movement over a ground plane toward obstacles lying in the observer’s path. Optical expansion was modulated by varying τ˙. The visual field was masked either centrally (peripheral vision) or peripherally (central vision) using masks ranging from 10° to 30° in diameter in steps of 10°. Participants were asked to indicate whether their approach would result in “collision” or “no collision” with the obstacles. Results showed that AD patients’ sensitivity to τ˙ was severely compromised, not only for central vision but also for peripheral vision, compared to age- and education-matched elderly controls. The results demonstrated that AD patients’ optic flow deficit is not limited to radial optic flow but includes also the optical pattern engendered by τ˙. Further deterioration in the capacity to extract τ˙ to determine potential collisions in conjunction with the inability to extract heading information from radial optic flow would exacerbate AD patients’ difficulties in navigation and visuospatial orientation. PMID:26635603

  16. Atrial Fibrillation and Coronary Artery Disease as Risk Factors of Retinal Artery Occlusion: A Nationwide Population-Based Study

    PubMed Central

    Yen, Ju-Chuan; Lin, Hsiu-Li; Hsu, Chia-An; Li, Yu-Chuan (Jack); Hsu, Min-Huei

    2015-01-01

    We use Taiwanese national health insurance research database (NHIRD) to investigate whether thrombolism (carotid artery disease (CAD) as a surrogate) or embolism (atrial fibrillation (AF) as a surrogate) plays roles in later retinal artery occlusion (RAO) development and examine their relative weights. The relative risks of RAO between AF and CAD patients and controls were compared by estimating the crude hazard ratio with logistic regression. Kaplan-Meier analysis was used to calculate the cumulative incidence rates of developing RAO, and a log-rank test was used to analyze the differences between the survival curves. Separate Cox proportional hazard regressions were done to compute the RAO-free rate after adjusting for possible confounding factors such as age and sex. The crude hazard ratios were 7.98 for the AF group and 5.27 for the CAD group, and the adjusted hazard ratios were 8.32 and 5.34 for the AF and CAD groups, respectively. The observation time with RAO-free was shorter for AF compared with CAD group (1490 versus 1819 days). AF and CAD were both risk factors for RAO with different hazard ratios. To tackle both AF and CAD is crucial for curbing RAO. PMID:26558268

  17. Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration.

    PubMed

    Wang, Jing; Saul, Alan; Roon, Penny; Smith, Sylvia B

    2016-06-28

    Retinal degenerative diseases are major causes of untreatable blindness, and novel approaches to treatment are being sought actively. Here we explored the activation of a unique protein, sigma 1 receptor (Sig1R), in the treatment of PRC loss because of its multifaceted role in cellular survival. We used Pde6β(rd10) (rd10) mice, which harbor a mutation in the rod-specific phosphodiesterase gene Pde6β and lose rod and cone photoreceptor cells (PRC) within the first 6 wk of life, as a model for severe retinal degeneration. Systemic administration of the high-affinity Sig1R ligand (+)-pentazocine [(+)-PTZ] to rd10 mice over several weeks led to the rescue of cone function as indicated by electroretinographic recordings using natural noise stimuli and preservation of cone cells upon spectral domain optical coherence tomography and retinal histological examination. The protective effect appears to result from the activation of Sig1R, because rd10/Sig1R(-/-) mice administered (+)-PTZ exhibited no cone preservation. (+)-PTZ treatment was associated with several beneficial cellular phenomena including attenuated reactive gliosis, reduced microglial activation, and decreased oxidative stress in mutant retinas. To our knowledge, this is the first report that activation of Sig1R attenuates inherited PRC loss. The findings may have far-reaching therapeutic implications for retinal neurodegenerative diseases. PMID:27298364

  18. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 7: lumbar fusion for intractable low-back pain without stenosis or spondylolisthesis.

    PubMed

    Eck, Jason C; Sharan, Alok; Ghogawala, Zoher; Resnick, Daniel K; Watters, William C; Mummaneni, Praveen V; Dailey, Andrew T; Choudhri, Tanvir F; Groff, Michael W; Wang, Jeffrey C; Dhall, Sanjay S; Kaiser, Michael G

    2014-07-01

    Establishing an appropriate treatment strategy for patients presenting with low-back pain, in the absence of stenosis or spondylolisthesis, remains a controversial subject. Inherent to this situation is often an inability to adequately identify the source of low-back pain to justify various treatment recommendations, such as lumbar fusion. The current evidence does not identify a single best treatment alternative for these patients. Based on a number of prospective, randomized trials, comparable outcomes, for patients presenting with 1- or 2-level degenerative disc disease, have been demonstrated following either lumbar fusion or a comprehensive rehabilitation program with a cognitive element. Limited access to such comprehensive rehabilitative programs may prove problematic when pursuing this alternative. For patients whose pain is refractory to conservative care, lumbar fusion is recommended. Limitations of these studies preclude the ability to present the most robust recommendation in support of lumbar fusion. A number of lesser-quality studies, primarily case series, also support the use of lumbar fusion in this patient population. PMID:24980584

  19. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association For European Cardiovascular Pathology: II. Noninflammatory degenerative diseases - nomenclature and diagnostic criteria.

    PubMed

    Halushka, Marc K; Angelini, Annalisa; Bartoloni, Giovanni; Basso, Cristina; Batoroeva, Lubov; Bruneval, Patrick; Buja, L Maximilian; Butany, Jagdish; d'Amati, Giulia; Fallon, John T; Gallagher, Patrick J; Gittenberger-de Groot, Adriana C; Gouveia, Rosa H; Kholova, Ivana; Kelly, Karen L; Leone, Ornella; Litovsky, Silvio H; Maleszewski, Joseph J; Miller, Dylan V; Mitchell, Richard N; Preston, Stephen D; Pucci, Angela; Radio, Stanley J; Rodriguez, E Rene; Sheppard, Mary N; Stone, James R; Suvarna, S Kim; Tan, Carmela D; Thiene, Gaetano; Veinot, John P; van der Wal, Allard C

    2016-01-01

    Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities. PMID:27031798

  20. Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

    PubMed

    Deng, Qian-xing; Ou, Yun-sheng; Zhu, Yong; Zhao, Zeng-hui; Liu, Bo; Huang, Qiu; Du, Xing; Jiang, Dian-ming

    2016-06-01

    This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF. PMID:27091044

  1. Retinal Detachment

    MedlinePlus

    ... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...

  2. Probabilistic retinal vessel segmentation

    NASA Astrophysics Data System (ADS)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  3. Neuropeptides in experimental and degenerative arthritis.

    PubMed

    Niissalo, S; Hukkanen, M; Imai, S; Törnwall, J; Konttinen, Y T

    2002-06-01

    Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). In contrast, osteoarthritis (OA) is considered to arise as a result of degeneration of the hyaline articular cartilage, which secondarily results in local inflammation and pain. However, it is possible that the age-related and predominant (compared to nociceptive nerves) degeneration of the proprioceptive, kinesthetic and vasoregulatory nerves can represent the primary pathogenic events. This leads to progressive damage of tissue with extremely poor capacity for self-regeneration. Inflammation, be it primary/autoimmune or secondary/degenerative, leads to peripheral sensitization and stimulation, which may further lead to central sensitization, neurogenic amplification of the inflammatory responses and activation of the neuro-endocrine axis. Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses. PMID:12114296

  4. Complement system in pathogenesis of AMD: dual player in degeneration and protection of retinal tissue.

    PubMed

    Kawa, Milosz P; Machalinska, Anna; Roginska, Dorota; Machalinski, Boguslaw

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly, especially in Western countries. Although the prevalence, risk factors, and clinical course of the disease are well described, its pathogenesis is not entirely elucidated. AMD is associated with a variety of biochemical abnormalities, including complement components deposition in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex. Although the complement system (CS) is increasingly recognized as mediating important roles in retinal biology, its particular role in AMD pathogenesis has not been precisely defined. Unrestricted activation of the CS following injury may directly damage retinal tissue and recruit immune cells to the vicinity of active complement cascades, therefore detrimentally causing bystander damage to surrounding cells and tissues. On the other hand, recent evidence supports the notion that an active complement pathway is a necessity for the normal maintenance of the neurosensory retina. In this scenario, complement activation appears to have beneficial effect as it promotes cell survival and tissue remodeling by facilitating the rapid removal of dying cells and resulting cellular debris, thus demonstrating anti-inflammatory and neuroprotective activities. In this review, we discuss both the beneficial and detrimental roles of CS in degenerative retina, focusing on the diverse aspects of CS functions that may promote or inhibit macular disease. PMID:25276841

  5. Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.

    PubMed

    Tracy, Christopher J; Sanders, Douglas N; Bryan, Jeffrey N; Jensen, Cheryl A; Castaner, Leilani J; Kirk, Mark D; Katz, Martin L

    2016-01-01

    A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis. PMID:26427461

  6. Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders

    PubMed Central

    Tracy, Christopher J.; Sanders, Douglas N.; Bryan, Jeffrey N.; Jensen, Cheryl A.; Castaner, Leilani J.; Kirk, Mark D.; Katz, Martin L.

    2016-01-01

    A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis. PMID:26427461

  7. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

    PubMed Central

    Kell, Douglas B

    2009-01-01

    Background The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. Review We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, since in some circumstances (especially the presence of poorly liganded iron) molecules that are nominally antioxidants can actually act as pro-oxidants. The reduction of redox

  8. Novel BAC mouse model of Huntington’s disease with 225 CAG repeats exhibits an early widespread and stable degenerative phenotype

    PubMed Central

    Wegrzynowicz, Michal; Bichell, Terry Jo; Soares, Barbara D.; Loth, Meredith K.; McGlothan, Jennifer L.; Alikhan, Fatima S.; Hua, Kegang; Coughlin, Jennifer M.; Holt, Hunter K.; Jetter, Christopher S.; Mori, Susumu; Pomper, Martin G.; Osmand, Alexander P.; Guilarte, Tomás R.; Bowman, Aaron B.

    2015-01-01

    BACKGROUND Unusually large CAG repeat expansions (>60) in exon one of Huntingtin (HTT) are invariably associated with a juvenile-onset form of Huntington’s disease (HD), characterized by a more extensive and rapidly progressing neuropathology than the more prevalent adult-onset form. However, existing mouse models of HD that express the full-length Htt gene with CAG repeat lengths associated with juvenile HD (ranging between ~75 to ~150 repeats in published models) exhibit selective neurodegenerative phenotypes more consistent with adult-onset HD. OBJECTIVE To determine if a very large CAG repeat (>200) in full-length Htt elicits neurodegenerative phenotypes consistent with juvenile HD. METHODS Using a bacterial artificial chromosome (BAC) system, we generated mice expressing full-length mouse Htt with ~225 CAG repeats under control of the mouse Htt promoter. Mice were characterized using behavioral, neuropathological, biochemical and brain imaging methods. RESULTS BAC-225Q mice exhibit phenotypes consistent with a subset of features seen in juvenile-onset HD: very early motor behavior abnormalities, reduced body weight, widespread and progressive increase in Htt aggregates, gliosis, and neurodegeneration. Early striatal pathology was observed, including reactive gliosis and loss of dopamine receptors, prior to detectable volume loss. HD-related blood markers of impaired energy metabolism and systemic inflammation were also increased. Aside from an age-dependent progression of diffuse nuclear aggregates at 6 months of age to abundant neuropil aggregates at 12 months of age, other pathological and motor phenotypes showed little to no progression. CONCLUSIONS The HD phenotypes present in animals 3 to 12 months of age make the BAC-225Q mice a unique and stable model of full-length mutant Htt associated phenotypes, including body weight loss, behavioral impairment and HD-like neurodegenerative phenotypes characteristic of juvenile-onset HD and/or late-stage adult

  9. PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila

    PubMed Central

    Huang, Z; Ren, S; Jiang, Y; Wang, T

    2016-01-01

    Calcium has an important role in regulating numerous cellular activities. However, extremely high levels of intracellular calcium can lead to neurotoxicity, a process commonly associated with degenerative diseases. Despite the clear role of calcium cytotoxicity in mediating neuronal cell death in this context, the pathological mechanisms remain controversial. We used a well-established Drosophila model of retinal degeneration, which involves the constitutively active TRPP365 channels, to study calcium-induced neurotoxicity. We found that the disruption of mitochondrial function was associated with the degenerative process. Further, increasing autophagy flux prevented cell death in TrpP365 mutant flies, and this depended on the PINK1/Parkin pathway. In addition, the retinal degeneration process was also suppressed by the coexpression of PINK1 and Parkin. Our results provide genetic evidence that mitochondrial dysfunction has a key role in the pathology of cellular calcium neurotoxicity. In addition, the results demonstrated that maintaining mitochondrial homeostasis via PINK1/Parkin-dependent mitochondrial quality control can potentially alleviate cell death in a wide range of neurodegenerative diseases. PMID:27054334

  10. Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study

    PubMed Central

    Polo, V; Satue, M; Rodrigo, M J; Otin, S; Alarcia, R; Bambo, M P; Fuertes, M I; Larrosa, J M; Pablo, L E; Garcia-Martin, E

    2016-01-01

    Objectives To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson's disease (PD). Methods Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. Results VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). Conclusions Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD. PMID:27154474

  11. Retinal vasculature classification using novel multifractal features

    NASA Astrophysics Data System (ADS)

    Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.

    2015-11-01

    Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.

  12. The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

    PubMed

    Arnold, Edith; Thebault, Stéphanie; Baeza-Cruz, German; Arredondo Zamarripa, David; Adán, Norma; Quintanar-Stéphano, Andrés; Condés-Lara, Miguel; Rojas-Piloni, Gerardo; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2014-01-29

    Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration. PMID:24478366

  13. Molecular genetics of retinitis pigmentosa.

    PubMed Central

    Farber, D. B.; Heckenlively, J. R.; Sparkes, R. S.; Bateman, J. B.

    1991-01-01

    Retinitis pigmentosa is a model for the study of genetic diseases. Its genetic heterogeneity is reflected in the different forms of inheritance (autosomal dominant, autosomal recessive, or X-linked) and, in a few families, in the presence of mutations in the visual pigment rhodopsin. Clinical and molecular genetic studies of these disorders are discussed. Animal models of retinal degeneration have been investigated for many years with the hope of gaining insight into the cause of photoreceptor cell death. Recently, the genes responsible for two of these animal disorders, the rds and rd mouse genes, have been isolated and characterized. The retinal degeneration of the rd mouse is presented in detail. The possible involvement of human analogues of these mouse genes in human retinal diseases is being investigated. Images PMID:1771877

  14. Fundus autofluorescence applications in retinal imaging.

    PubMed

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-05-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  15. Fundus autofluorescence applications in retinal imaging

    PubMed Central

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-01-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  16. Macular Thickness Measurements with Frequency Domain-OCT for Quantification of Retinal Neural Loss and its Correlation with Cognitive Impairment in Alzheimerʼs Disease

    PubMed Central

    Cunha, Leonardo Provetti; Lopes, Luciana Cheker; Costa-Cunha, Luciana Virgínia Ferreira; Costa, Carolina Ferreira; Pires, Leopoldo Antônio; Almeida, Ana Laura Maciel; Monteiro, Mário Luiz Ribeiro

    2016-01-01

    Purpose To evaluate the ability of frequency domain optical coherence tomography (fd-OCT) to estimate retinal neural loss in eyes with Alzheimer’s disease (AD). We also verified the existence of a correlation between AD-related cognitive impairment and macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements. Methods fd-OCT scans were obtained from 45 eyes of 24 patients with AD and 48 control eyes. Peripapillary RNFL, macular full-thickness and segmented inner macular thickness parameters were calculated. The inner macular parameters included macular retinal nerve fiber layer (mRNFL) thickness, ganglion cell layer (GCL) plus inner plexiform layer thickness (GCL+), and RNFL plus GCL+ thickness (GCL++). The Mini-Mental State Examination (MMSE) was used to assess cognition in all subjects. The two groups were compared and the relationship between MMSE scores and fd-OCT measurements was verified. Results Average, superior and inferior quadrant RNFL thickness parameters and all but one of the nine full-thickness macular measurements were significantly reduced in AD patients compared to controls. The segmented layers, GCL+ and GCL++ were significantly reduced in AD eyes. A significant correlation was found between most fd-OCT parameters (especially macular thickness measurements) and MMSE scores. Conclusions Most fd-OCT peripapillary RNFL and macular full-thickness and segmented inner retinal layers parameters were reduced in AD eyes compared to controls. Moreover, neuronal loss, especially as reflected in macular parameters, correlated well with cognitive impairment in AD. Our results suggest that fd-OCT could be a potentially useful diagnostic tool in the evaluation and follow-up of AD patients. PMID:27104962

  17. Leaves of Persimmon (Diospyros kaki Thunb.) Ameliorate N-Methyl-N-nitrosourea (MNU)-Induced Retinal Degeneration in Mice.

    PubMed

    Kim, Kyung-A; Kang, Suk Woo; Ahn, Hong Ryul; Song, Youngwoo; Yang, Sung Jae; Jung, Sang Hoon

    2015-09-01

    The purpose of the study was to investigate the protective effects of the ethanol extract of Diospyros kaki (EEDK) persimmon leaves to study N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. EEDK was orally administered after MNU injection. Retinal layer thicknesses were significantly increased in the EEDK-treated group compared with the MNU-treated group. The outer nuclear layer was preserved in the retinas of EEDK-treated mice. Moreover, EEDK treatment reduced the MNU-dependent up-regulation of glial fibrillary acidic protein (GFAP) and nestin expression in Müller and astrocyte cells. EEDK treatment also inhibited MNU-dependent down-regulation of rhodopsin expression. Quercetin exposure significantly attenuated the negative effects of H2O2 in R28 cells, suggesting that quercetin can act in an antioxidative capacity. Thus, EEDK may be considered as an agent for treating or preventing degenerative retinal diseases, such as retinitis pigmentosa and age-related macular degeneration. PMID:26260943

  18. Biomechanics of Degenerative Spinal Disorders

    PubMed Central

    Iorio, Justin A.; Jakoi, Andre M.

    2016-01-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  19. Biomechanics of Degenerative Spinal Disorders.

    PubMed

    Iorio, Justin A; Jakoi, Andre M; Singla, Anuj

    2016-04-01

    The spine has several important functions including load transmission, permission of limited motion, and protection of the spinal cord. The vertebrae form functional spinal units, which represent the smallest segment that has characteristics of the entire spinal column. Discs and paired facet joints within each functional unit form a three-joint complex between which loads are transmitted. Surrounding the spinal motion segment are ligaments, composed of elastin and collagen, and joint capsules which restrict motion to within normal limits. Ligaments have variable strengths and act via different lever arm lengths to contribute to spinal stability. As a consequence of the longer moment arm from the spinous process to the instantaneous axis of rotation, inherently weaker ligaments (interspinous and supraspinous) are able to provide resistance to excessive flexion. Degenerative processes of the spine are a normal result of aging and occur on a spectrum. During the second decade of life, the intervertebral disc demonstrates histologic evidence of nucleus pulposus degradation caused by reduced end plate blood supply. As disc height decreases, the functional unit is capable of an increased range of axial rotation which subjects the posterior facet capsules to greater mechanical loads. A concurrent change in load transmission across the end plates and translation of the instantaneous axis of rotation further increase the degenerative processes at adjacent structures. The behavior of the functional unit is impacted by these processes and is reflected by changes in the stress-strain relationship. Back pain and other clinical symptoms may occur as a result of the biomechanical alterations of degeneration. PMID:27114783

  20. Preservation of retinotopic map in retinal degeneration.

    PubMed

    Xie, John; Wang, Gene-Jack; Yow, Lindy; Humayun, Mark S; Weiland, James D; Cela, Carlos J; Jadvar, Hossein; Lazzi, Gianluca; Dhrami-Gavazi, Elona; Tsang, Stephen H

    2012-05-01

    Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss. PMID:22685713

  1. A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse.

    PubMed

    Bhadresha, Ashwin; Lawrence, Owen John; McCarthy, Michael J H

    2016-06-01

    Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone (n = 58) and DDD with disk herniation (n = 107). A grid was randomly applied to the axial scans at the L3-L4, L4-L5, and L5-S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women (p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability (p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3-L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness. PMID:27190744

  2. A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse

    PubMed Central

    Bhadresha, Ashwin; Lawrence, Owen John; McCarthy, Michael J. H.

    2016-01-01

    Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone (n = 58) and DDD with disk herniation (n = 107). A grid was randomly applied to the axial scans at the L3–L4, L4–L5, and L5–S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women (p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability (p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3–L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness. PMID:27190744

  3. Cell Models to Study Regulation of Cell Transformation in Pathologies of Retinal Pigment Epithelium

    PubMed Central

    Kuznetsova, Alla V.; Aleksandrova, Maria A.

    2014-01-01

    The retinal pigment epithelium (RPE) plays a key role in the development of many eye diseases leading to visual impairment and even blindness. Cell culture models of pathological changes in the RPE make it possible to study factors responsible for these changes and signaling pathways coordinating cellular and molecular mechanisms of cell interactions under pathological conditions. Moreover, they give an opportunity to reveal target cells and develop effective specific treatment for degenerative and dystrophic diseases of the retina. In this review, data are presented on RPE cell sources for culture models, approaches to RPE cell culturing, phenotypic changes of RPE cells in vitro, the role of signal pathways, and possibilities for their regulation in pathological processes. PMID:25177495

  4. Stem Cell Sources and Their Potential for the Treatment of Retinal Degenerations.

    PubMed

    Canto-Soler, Valeria; Flores-Bellver, Miguel; Vergara, M Natalia

    2016-04-01

    Stem cells offer unprecedented opportunities for the development of strategies geared toward the treatment of retinal degenerative diseases. A variety of cellular sources have been investigated for various potential clinical applications, including tissue regeneration, disease modeling, and screening for non-cell-based therapeutic agents. As the field transitions from more than a decade of preclinical research to the first phase I/II clinical trials, we provide a concise overview of the stem cell sources most commonly used, weighing their therapeutic potential on the basis of their technical strengths/limitations, their ethical implications, and the extent of the progress achieved to date. This article serves as a framework for further in-depth analyses presented in the following chapters of this Special Issue. PMID:27116661

  5. A novel function of Huntingtin in the cilium and retinal ciliopathy in Huntington's disease mice.

    PubMed

    Karam, Alice; Tebbe, Lars; Weber, Chantal; Messaddeq, Nadia; Morlé, Laurette; Kessler, Pascal; Wolfrum, Uwe; Trottier, Yvon

    2015-08-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by the toxic expansion of polyglutamine in the Huntingtin (HTT) protein. The pathomechanism is complex and not fully understood. Increasing evidence indicates that the loss of normal protein function also contributes to the pathogenesis, pointing out the importance of understanding the physiological roles of HTT. We provide evidence for a novel function of HTT in the cilium. HTT localizes in diverse types of cilia--including 9 + 0 non-motile sensory cilia of neurons and 9 + 2 motile multicilia of trachea and ependymal cells--which exert various functions during tissue development and homeostasis. In the photoreceptor cilium, HTT is present in all subciliary compartments from the base of the cilium and adjacent centriole to the tip of the axoneme. In HD mice, photoreceptor cilia are abnormally elongated, have hyperacetylated alpha-tubulin and show mislocalization of the intraflagellar transport proteins IFT57 and IFT88. As a consequence, intraflagellar transport function is perturbed and leads to aberrant accumulation of outer segment proteins in the photoreceptor cell bodies and disruption of outer segment integrity, all of which precede overt cell death. Strikingly, endogenous mouse HTT is strongly reduced in cilia and accumulates in photoreceptor cell bodies, suggesting that HTT loss function contributes to structural and functional defects of photoreceptor cilia in HD mouse. Our results indicate that cilia pathology participates in HD physiopathology and may represent a therapeutic target. PMID:25989602

  6. Progranulin, a Major Secreted Protein of Mouse Adipose-Derived Stem Cells, Inhibits Light-Induced Retinal Degeneration

    PubMed Central

    Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tomohiro; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru

    2014-01-01

    Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC-conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte-conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte-conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina. PMID:24233842

  7. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families

    PubMed Central

    Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N.; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

    2015-01-01

    Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. PMID:26147992

  8. Using Nutrition Against Aging and Degenerative Disease.

    ERIC Educational Resources Information Center

    Rokosz, Francis M.

    A review of historical and research literature presents various perspectives on the growing controversy surrounding the use of vitamin and mineral supplements to maintain good health and for preventive health care. Several points are made in opposition to many health professionals' opinions that most nutritional supplements are unnecessary.…

  9. Cartilage tissue engineering for degenerative joint disease.

    PubMed

    Nesic, Dobrila; Whiteside, Robert; Brittberg, Mats; Wendt, David; Martin, Ivan; Mainil-Varlet, Pierre

    2006-05-20

    Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed. PMID:16574268

  10. Retinal detachment

    MedlinePlus

    ... of the first symptoms of new flashes of light and floaters. ... diabetes. See your eye care specialist once a year. You may need more frequent visits if you have risk factors for retinal detachment. Be alert to symptoms of new flashes of light and floaters.

  11. Small Animal Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  12. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    PubMed

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy. PMID:22683799

  13. Identification of a Common Non-Apoptotic Cell Death Mechanism in Hereditary Retinal Degeneration

    PubMed Central

    Sahaboglu, Ayse; Kranz, Katharina; Michalakis, Stylianos; Farinelli, Pietro; Koch, Susanne; Koch, Fred; Cottet, Sandra; Janssen-Bienhold, Ulrike; Dedek, Karin; Biel, Martin; Zrenner, Eberhart; Euler, Thomas; Ekström, Per; Ueffing, Marius; Paquet-Durand, François

    2014-01-01

    Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are activation of histone deacetylase, poly-ADP-ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of alternative cell death mechanisms in inherited retinal degeneration and provides a rational basis for the design of mutation-independent treatments. PMID:25392995

  14. Risk of Tractional Retinal Detachment Following Intravitreal Bevacizumab Along with Subretinal Fluid Drainage and Cryotherapy for Stage 3B Coats’ Disease

    PubMed Central

    Bhat, Vishalakshi; D’Souza, Palmeera; Shah, Parag K.; Narendran, V.

    2016-01-01

    Purpose: To review the surgical outcomes of intravitreal bevacizumab (IVB) along with subretinal fluid drainage with cryotherapy in patients with stage 3B Coats’ disease. Materials and Methods: A retrospective study of seven cases of stage 3B Coats’ disease, who underwent subretinal fluid drainage with cryopexy, from May 2011 to March 2014. Five eyes received additional IVB at the end of surgery. Green laser therapy was performed on telangiectatic vessels postoperatively. Results: The mean age was 34 months (range, 10-84 months). Mean follow-up was 19 months. Six patients (85.7%) had an attached retina at final follow-up. Three out of four patients (75%) that received IVB developed tractional retinal detachments (TRDs). Two eyes that did not receive bevacizumab did not develop any traction. None progressed to neovascular glaucoma or phthisis bulbi. Conclusion: Simultaneous injection of bevacizumab along with subretinal drainage and cryotherapy for advanced Coats’ disease could not avoid TRD. PMID:27162454

  15. Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population

    SciTech Connect

    Van Soest, S.; Ingeborgh Van Den Born, L.; Bergen, A.A.B.

    1994-08-01

    Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the arRP patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located at 1q31-q32.1, and RP12 ({Zeta}{sub max} = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of the family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12)-D1S53-1qter ({Zeta}{sub max} = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully. 35 refs., 5 figs.

  16. Other Retinal Diseases

    MedlinePlus

    ... Campaign to End Blindness Other Ways to Fight Blindness Corporate Support Volunteer Take Action Honor a Loved ... taking place nationwide. Join Us We Are Ending Blindness The urgent mission of the Foundation Fighting Blindness ...

  17. Retinal Detachment Vision Simulator

    MedlinePlus

    ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment Vision Simulator Mar. 01, 2016 How does a detached or torn retina affect your vision? If a retinal tear is occurring, you may ...

  18. Retinitis Pigmentosa and Education Issues

    ERIC Educational Resources Information Center

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  19. Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs.

    PubMed

    Smith, G K; Gregor, T P; Rhodes, W H; Biery, D N

    1993-07-01

    A 3-year prospective study of large-breed dogs (4 months to 3 years of age) was conducted to evaluate the influence of radiographic positioning and age on coxofemoral joint (hip) laxity, subjective hip score, and development of degenerative joint disease (DJD). The dogs (n = 142) were breeder- or client-owned and represented 14 breeds. With dogs under heavy sedation, hips were radiographed in the standard hip-extended position and in the new compression/distraction position at 4, 6, 12, 24, and 36 months of age. The standard hip-extended radiographic view was evaluated by 3 methods: subjective evaluation by a board-certified veterinary radiologist (WHR), according to the standard 7-point Orthopedic Foundation for Animals (OFA) scoring scheme (OFA/WHR); joint laxity quantitation, using the Norberg angle (NA) method; and subjective scoring by a veterinary orthopedic surgeon for radiographic evidence of DJD. The hips in the distraction radiographic view were evaluated for passive hip laxity, as measured by use of a unitless distraction index (DI). Results of the study indicated that at a specific age (4, 6, 12, 24, or 36 months), all methods of hip evaluation correlated with each other at a moderate level (P < 0.05). The strength of contemporaneous correlation tended to increase with age of evaluation. Longitudinally, the between-method correlations were usually significant (P < 0.05), but not at a sufficiently high level to permit reliable between-method prediction. Prospective intraclass (within-method) statistical analysis of the various hip-scoring methods indicated that DI was superior to NA and OFA/WHR in comparability of score over time. The intraclass correlation coefficient ranged from 0.55 to 0.91 for DI in contrast to 0.40 to 0.78 for NA, and 0.06 to 0.39 for OFA/WHR over the age intervals of the study. For reference, the highest Kappa of 0.39 for the subjective OFA/WHR scoring reflected a maximal level of agreement between time intervals, only slightly

  20. Outcomes observed during a 1-year clinical and radiographic follow-up of patients treated for 1- or 2-level cervical degenerative disease using a biodegradable anterior cervical plate.

    PubMed

    Chen, Mengcun; Yang, Shuhua; Yang, Cao; Xu, Weihua; Ye, Shunan; Wang, Jing; Feng, Yong; Yang, Wen; Liu, Xianzhe

    2016-08-01

    OBJECTIVE The purpose of this study was to present an initial surgical experience in the management of 1- or 2-level degenerative disc disease of the cervical spine using biodegradable anterior cervical plates (bACPs) in anterior cervical discectomy and fusion (ACDF). The authors also aimed to provide insight into this critical and controversial clinical issue by clarifying outcomes for patients receiving bACPs and by comparing their outcomes with those achieved using a traditional metallic anterior cervical plate (mACP) implant. METHODS A retrospective review was conducted for 2 series of patients who had undergone ACDF using either bACP (31 patients, 38 segments) or mACP (47 patients, 57 segments) instrumentation. The patients were followed up for a mean 13.5 ± 0.9 months (range 12-18 months) in the bACP group and 14.8 ± 1.5 months (range 14-22 months) in the mACP group. Clinical outcomes were determined according to scores on the visual analog scale (VAS), the modified Japanese Orthopaedic Association (mJOA) scoring system, and Odom's criteria. Radiological images were used to assess fusion rates, intervertebral height, Cobb's angle, and the width of prevertebral soft tissue. RESULTS Both VAS and mJOA scores were significantly improved at each follow-up in both groups. Excellent or good results according to Odom's criteria were achieved in 93.5% (29/31) of patients in the bACP group and 93.6% (44/47) of patients in the mACP group. At 6 months postoperatively, the fusion rate was 94.7% (36/38) in the bACP group and 96.5% (55/57) in the mACP group, but subsidence of the intervertebral space at the surgical level was more evident in the bACP group. Angulation, as measured by Cobb's angle, demonstrated obvious healing in both groups, while better maintenance was observed in the mACP group. The local inflammatory reaction was uneventful during follow-up. Dysphonia and dysphagia were observed in both groups during the follow-up. CONCLUSIONS The relatively comparable

  1. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  2. Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

    PubMed Central

    2012-01-01

    Background Inherited retinal disorders are clinically and genetically heterogeneous with more than 150 gene defects accounting for the diversity of disease phenotypes. So far, mutation detection was mainly performed by APEX technology and direct Sanger sequencing of known genes. However, these methods are time consuming, expensive and unable to provide a result if the patient carries a new gene mutation. In addition, multiplicity of phenotypes associated with the same gene defect may be overlooked. Methods To overcome these challenges, we designed an exon sequencing array to target 254 known and candidate genes using Agilent capture. Subsequently, 20 DNA samples from 17 different families, including four patients with known mutations were sequenced using Illumina Genome Analyzer IIx next-generation-sequencing (NGS) platform. Different filtering approaches were applied to identify the genetic defect. The most likely disease causing variants were analyzed by Sanger sequencing. Co-segregation and sequencing analysis of control samples validated the pathogenicity of the observed variants. Results The phenotype of the patients included retinitis pigmentosa, congenital stationary night blindness, Best disease, early-onset cone dystrophy and Stargardt disease. In three of four control samples with known genotypes NGS detected the expected mutations. Three known and five novel mutations were identified in NR2E3, PRPF3, EYS, PRPF8, CRB1, TRPM1 and CACNA1F. One of the control samples with a known genotype belongs to a family with two clinical phenotypes (Best and CSNB), where a novel mutation was identified for CSNB. In six families the disease associated mutations were not found, indicating that novel gene defects remain to be identified. Conclusions In summary, this unbiased and time-efficient NGS approach allowed mutation detection in 75% of control cases and in 57% of test cases. Furthermore, it has the possibility of associating known gene defects with novel phenotypes

  3. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical p