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. 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

  5. Vitamin A derivatives as treatment options for retinal degenerative diseases.

    PubMed

    Perusek, Lindsay; Maeda, Tadao

    2013-07-12

    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.

  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 Central

    Schubert, Timm; Wissinger, Bernd

    2015-01-01

    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. Degenerative retinal disorders

    SciTech Connect

    Hollyfield, J.G. Anderson, R.E. LaVail, M.M. . Dept. of Anatomy)

    1987-01-01

    This book contains papers divided among three sections. Some of the paper titles are: Molecular Genetics of Gyrate Atrophy; Molecular Site of Expression and Genetic Interaction of the rd and the rds Loci in the Retina of the Mouse; and Studies on Abnormal Cyclic GMP Metabolism in Animal Models of Retinal Degeneration: Genetic Relationships and Cellular Compartmentalization.

  12. 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 ...

  13. Cone specific promoter for use in gene therapy of retinal degenerative diseases.

    PubMed

    Dyka, Frank M; Boye, Sanford L; Ryals, Renee C; Chiodo, Vince A; Boye, Shannon E; Hauswirth, William W

    2014-01-01

    Achromatopsia (ACHM) is caused by a progressive loss of cone photoreceptors leading to color blindness and poor visual acuity. Animal studies and human clinical trials have shown that gene replacement therapy with adeno-associate virus (AAV) is a viable treatment option for this disease. Although there have been successful attempts to optimize capsid proteins for increased specificity, it is simpler to restrict expression via the use of cell type-specific promoters. To target cone photoreceptors, a chimeric promoter consisting of an enhancer element of interphotoreceptor retinoid-binding protein promoter and a minimal sequence of the human transducin alpha-subunit promoter (IRBPe/GNAT2) was created. Additionally, a synthetic transducin alpha-subunit promoter (synGNAT2/GNAT2) containing conserved sequence blocks located downstream of the transcriptional start was created. The strength and specificity of these promoters were evaluated in murine retina by immunohistochemistry. The results showed that the chimeric, (IRBPe/GNAT2) promoter is more efficient and specific than the synthetic, synGNAT2/GNAT2 promoter. Additionally, IRBPe/GNAT2-mediated expression was found in all cone subtypes and it was improved over existing promoters currently used for gene therapy of achromatopsia. PMID:24664760

  14. Retinal and optic nerve diseases.

    PubMed

    Margalit, Eyal; Sadda, Srinivas R

    2003-11-01

    A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device.

  15. Transplantation of Embryonic and Induced Pluripotent Stem Cell-Derived 3D Retinal Sheets into Retinal Degenerative Mice

    PubMed Central

    Assawachananont, Juthaporn; Mandai, Michiko; Okamoto, Satoshi; Yamada, Chikako; Eiraku, Mototsugu; Yonemura, Shigenobu; Sasai, Yoshiki; Takahashi, Masayo

    2014-01-01

    Summary In this article, we show that mouse embryonic stem cell- or induced pluripotent stem cell-derived 3D retinal tissue developed a structured outer nuclear layer (ONL) with complete inner and outer segments even in an advanced retinal degeneration model (rd1) that lacked ONL. We also observed host-graft synaptic connections by immunohistochemistry. This study provides a “proof of concept” for retinal sheet transplantation therapy for advanced retinal degenerative diseases. PMID:24936453

  16. Biosynthesis, characterization, and efficacy in retinal degenerative diseases of lens epithelium-derived growth factor fragment (LEDGF1-326), a novel therapeutic protein.

    PubMed

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

    2013-06-14

    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.

  17. Widespread retinal degenerative disease mutation (rdAc) discovered among a large number of popular cat breeds.

    PubMed

    Menotti-Raymond, M; David, V A; Pflueger, S; Roelke, M E; Kehler, J; O'Brien, S J; Narfström, K

    2010-10-01

    The recent discovery of a mutational variant in the CEP290 gene (CEP290: IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence, frequency and clinical consequence of rdAc. The rdAc allele displayed widespread distribution, observed in 16/43 (37%) breeds, exhibiting a high allele frequency (∼33%) in North American and European Siamese populations. Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.1E-6), with clinical disease similar to affected Abyssinians/Somalis. This retinal degeneration has not been reported in breeds other than the Abyssinian/Somali and poses a significant health risk particularly in the Siamese breed group. Alertness of the veterinary community and the present availability of commercial diagnostic testing could synergistically enable breeders to reduce the incidence of rdAc blindness in pure-bred cat populations.

  18. Degenerative disease of the spine.

    PubMed

    Gallucci, Massimo; Limbucci, Nicola; Paonessa, Amalia; Splendiani, Alessandra

    2007-02-01

    Degenerative disease of the spine is a definition that includes a wide spectrum of degenerative abnormalities. Degeneration involves bony structures and the intervertebral disk, although many aspects of spine degeneration are strictly linked because the main common pathogenic factor is identified in chronic overload. During life the spine undergoes continuous changes as a response to physiologic axial load. These age-related changes are similar to pathologic degenerative changes and are a common asymptomatic finding in adults and elderly persons. A mild degree of degenerative changes is paraphysiologic and should be considered pathologic only if abnormalities determine symptoms. Imaging allows complete evaluation of static and dynamic factors related to degenerative disease of the spine and is useful in diagnosing the different aspects of spine degeneration.

  19. Mitochondrial dysfunction in retinal diseases.

    PubMed

    Barot, Megha; Gokulgandhi, Mitan R; Mitra, Ashim K

    2011-12-01

    The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases.

  20. 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.

  1. Genetic pediatric retinal diseases.

    PubMed

    Say, Emil Anthony T

    2014-12-01

    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. PMID:27625880

  2. [Dysexecutive syndromes and degenerative diseases].

    PubMed

    Pillon, B; Czernecki, V; Dubois, B

    2004-04-01

    A dysexecutive syndrome is observed not only in frontotemporal lobar degeneration, but also in subcortical degenerative diseases, and even in Alzheimer's disease whose lesions predominate in temporoparietal associative areas. The association between a dysexecutive syndrome and various cerebral localisations may be explained by the fact that cognitive and behavioral organisation recruits anatomofunctional frontostriatal and frontoparietal circuits. Both animal experimentation and human clinical observation argue in favour of a functional continuity and complementarity among these loops. The prefrontal cortex would be particularly needed in new situations, to inhibit old programs of action not adapted to the present context and to elaborate new ones; the basal ganglia would be rather required by the repetition of the situation to progressively transform the new program in routine. If we refer to Shallice model, we can hypothesize that optimal executive functions require the preservation not only of the Supervisory Attentional System, mainly dependent on the prefrontal cortex, but also of the Contention Scheduling, recruiting the basal ganglia, and of the Schemas of Action, represented in parietal and premotor areas. Therefore, the neuropsychological assessment of patients with degenerative diseases contributes to the understanding of the anatomofunctional architecture of executive functions.

  3. Serial block face-scanning electron microscopy: a method to study retinal degenerative phenotypes

    PubMed Central

    Mustafi, Debarshi; Kikano, Sandra; Palczewski, Krzysztof

    2014-01-01

    Retinal degenerative conditions can vary in their clinical presentation and often present with subtle phenotypic features before the onset of clinically overt disease. To capture these isolated events that precipitate disease, large representative areas of the retina must be imaged at high resolution. Compared to light microscopic methods, traditional electron microscopy can provide images at sufficient resolution to detect subtle pathologic changes in the retina, but are limited to the area being surveyed. The advent of serial block face-scanning electron microscopy (SBFSEM) provides the resolution needed with the unprecedented advantage of imaging large volumes of retinal tissue. Furthermore, automation of SBF-SEM bypasses errors from manual sectioning and can produce reliable serial sections as thin as 25 nanometers. Moreover, the three-dimensional structures generated can highlight cellular connectivity and interactions in the retina and reveal pathological changes. Using SBF-SEM, we have identified subtle phenotypic features in mouse models of various human retinal dystrophies. This method will allow researchers to identify and monitor the time course of these pathologies. Here, we summarize the SBF-SEM methodology and its application to mouse models of retinal degeneration. PMID:25621191

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

  10. Degenerative spinal disease in large felids.

    PubMed

    Kolmstetter, C; Munson, L; Ramsay, E C

    2000-03-01

    Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions. PMID:10884118

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Neuromuscular exercise as treatment of degenerative knee disease.

    PubMed

    Ageberg, Eva; Roos, Ewa M

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as traditionally used strength or aerobic training but aims to target more closely the sensorimotor deficiencies and functional instability associated with the degenerative knee disease than traditionally used training methods.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. Prospects of Stem Cells for Retinal Diseases.

    PubMed

    Ng, Tsz Kin; Lam, Dennis S C; Cheung, Herman S

    2013-01-01

    Retinal diseases, including glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration, are the leading causes of irreversible visual impairment and blindness in developed countries. Traditional and current treatment regimens are based on surgical or medical interventions to slow down the disease progression. However, the number of retinal cells would continue to diminish, and the diseases could not be completely cured. There is an emerging role of stem cells in retinal research. The stem cell therapy on retinal diseases is based on 2 theories: cell replacement therapy and neuroprotective effect. The former hypothesizes that new retinal cells could be regenerated from stem cells to substitute the damaged cells in the diseased retina, whereas the latter believes that the paracrine effects of stem cells modulate the microenvironments of the diseased retina so as to protect the retinal neurons. This article summarizes the choice of stem cells in retinal research. Moreover, the current progress of retinal research on stem cells and the clinical applications of stem cells on retinal diseases are reviewed. In addition, potential challenges and future prospects of retinal stem cell research are discussed.

  2. Destructive discovertebral degenerative disease of the lumbar spine.

    PubMed

    Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

    2012-09-01

    The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

  3. Curcumin, a potential therapeutic candidate for retinal diseases.

    PubMed

    Wang, Lei-Lei; Sun, Yue; Huang, Kun; Zheng, Ling

    2013-09-01

    Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

  4. 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

  5. Effects of interspinous spacers on lumbar degenerative disease.

    PubMed

    Zhou, Dong; Nong, Lu-Ming; DU, Rui; Gao, Gong-Ming; Jiang, Yu-Qing; Xu, Nan-Wei

    2013-03-01

    The present study aimed to evaluate the early effects of interspinous spacers on lumbar degenerative disease. The clinical outcomes of 23 patients with lumbar degenerative disease, treated using interspinous spacer implantation alone or combined with posterior lumbar fusion, were retrospectively studied and assessed with a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Pre-operative and post-operative interspinous distance, disc space height, foraminal width and height and segmental lordosis were determined. The early effects and complications associated with the interspinous spacers were recorded. The surgical procedures performed with the in-space treatment were easy and minimally invasive. The VAS scores and ODI were improved post-operatively compared with pre-operatively. Significant changes in the interspinous distance, disc space height, foraminal width and height and segmental lordosis were noted. In-space treatment for degenerative lumbar disease is easy and safe, with good early effects. The in-space system provides an alternative treatment for lumbar degenerative disease.

  6. 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.

  7. 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

  8. 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

  9. Boundary lubricating ability of synovial fluid in degenerative joint disease.

    PubMed

    Davis, W H; Lee, S L; Sokoloff, L

    1978-01-01

    The boundary lubricating ability of eleven synovial fluids was measured in a miniaturized latex--glass test system. The specimens were obtained at necropsy from knees in which the degree of degenerative joint disease varied from none to very severe. The lubricating ability of the fluid was independent of the viscosity over a wide range of shear rates. It was not diminished even in advanced lesions. In two additional fluids, the mucin clot was poor; the lubricating ability of one of these was compromised. Thus, although degenerative joint disease, during its quiescent stages, is not associated with defective synovial lubrication, the possibility that transient defects might lead to cartilage wear during life has not been excluded. The measurements are believed to be valid indicators of boundary lubricating ability under physiological conditions despite the fact that the test surfaces were not cartilaginous and the loading was relatively low (up to 47 pounds per square inch).

  10. 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

  11. Retinoids for Treatment of Retinal Diseases

    PubMed Central

    Palczewski, Krzysztof

    2010-01-01

    Knowledge about retinal photoreceptor signal transduction and the visual cycle required for normal eyesight has expanded exponentially over the past decade. Substantial progress in human genetics has allowed identification of candidate genes and complex networks underlying inherited retinal diseases. Natural mutations in animal models that mimic human diseases have been characterized and advanced genetic manipulation now permits generation of small mammalian models of human retinal diseases. Pharmacological repair of defective visual processes in animal models not only validates their involvement in vision but also provides great promise for developing improved therapies for the millions that are progressing towards blindness or are almost completely robbed of eyesight. PMID:20435355

  12. 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.

  13. [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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Total Disc Replacement in Lumbar Degenerative Disc Diseases.

    PubMed

    Park, Chun Kun

    2015-11-01

    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

  1. 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

  2. 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.

  3. 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.

  4. [Severe hereditary retinal diseases in childhood].

    PubMed

    Lorenz, B

    1996-01-01

    In dependence on the various statistics, hereditary causes are identified in up to 50% of the visually handicapped and blind school children. Most common are retinal disorders, which account for 15 to 55%. The most important diseases are briefly reviewed: Leber's congenital amaurosis, rod monochromacy, blue cone monochromacy, congenital stationary night blindness (CSNB), X-linked retinitis pigmentosa, Usher syndromes, Bardet-Biedl syndrome, juvenile neuronal ceroid lipofuscinosis Spielmeyer-Vogt, the various forms of albinism, exsudative vitreoretinopathies including Norrie's disease, as well as Stargardt's macular dystrophy, vitelliform macular dystrophy, and hereditary retinoblastoma. In addition to the clinical symptoms, general genetic principles are stressed, such as mode of inheritance, heterogeneity, expressivity, penetrance, age at manifestation, X-chromosomal gene inactivation, and variability. They all have to be taken into account to correctly establish the diagnosis, to identify family members at risk, and to provide adequate genetic counselling. An overview of the actual molecular genetics of the various retinal disorders is also given.

  5. Degenerative spine disease : pathologic findings in 985 surgical specimens.

    PubMed

    Pytel, Peter; Wollmann, Robert L; Fessler, Richard G; Krausz, Thomas N; Montag, Anthony G

    2006-02-01

    A number of pathologic changes have been reported in spinal surgery specimens. The frequency of many of these is not well defined. We retrospectively reviewed the histologic features of 985 extradural spinal surgery specimens. Of the cases, 1.6% were identified clinically as synovial cysts. In addition, synovial tissue was seen in another 5.3% of cases, often embedded within disk material. Neovascularization of disk tissue was present in 8.1% of cases, chondrocyte clusters in 18.3%, and calcium pyrophosphate crystals in 2.8%, predominantly within disk material. With the exception of crystal deposits, all of these changes were significantly more common in the lumbar spine. A better understanding of cell-based degenerative changes will become essential with increasing research into cell-based therapies for spinal disk disease. We report data on the frequency of different pathologic changes and describe synovial metaplasia as a reactive change not previously reported.

  6. 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

  7. Health assessment of environmental pollutants: proliferative and degenerative diseases

    SciTech Connect

    Stuart, B.O.

    1988-12-01

    In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed.

  8. 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

  9. Concise Review: Making Stem Cells Retinal: Methods for Deriving Retinal Pigment Epithelium and Implications for Patients With Ocular Disease.

    PubMed

    Leach, Lyndsay L; Clegg, Dennis O

    2015-08-01

    Stem cells provide a potentially unlimited source of cells for treating a plethora of human diseases. Regenerative therapies for retinal degenerative diseases are at the forefront of translation to the clinic, with stem cell-derived retinal pigment epithelium (RPE)-based treatments for age-related macular degeneration (AMD) already showing promise in human patients. Despite our expanding knowledge of stem cell biology, methods for deriving cells, including RPE have remained inefficient. Thus, there has been a push in recent years to develop more directed approaches to deriving cells for therapy. In this concise review, we summarize recent efforts that have been successful in improving RPE derivation efficiency by directing differentiation from human pluripotent stem cells using developmental cues important for normal RPE specification and maturation in vivo. In addition, potential obstacles for clinical translation are discussed. Finally, we review how derivation of RPE from human induced pluripotent stem cells (hiPSCs) provides in vitro models for studying mechanisms of retinal disease and discovering new avenues for treatment.

  10. 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

  11. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  12. Vertebral degenerative disc disease severity evaluation using random forest classification

    NASA Astrophysics Data System (ADS)

    Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.

    2014-03-01

    Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.

  13. Eyes open to stem cells: safety trial may pave the way for cell therapy to treat retinal disease in patients

    PubMed Central

    2011-01-01

    A clinical trial using human embryonic stem cell (hESC) therapy for an inherited retinal degenerative disease is about to commence. The Advanced Cell Technology (ACT) trial will treat patients with Stargardt's macular dystrophy using transplanted retinal pigment epithelium derived from hESCs. Currently, no effective treatment is available for Stargardt's disease so a stem cell-based therapy that can slow progression of this blinding condition could represent a significant breakthrough. While there are some hurdles to clear, the ACT trial is a fine example of translational research that could eventually pave the way for a range of stem cell therapies for the retina and other tissues. PMID:22152341

  14. Molecular Imaging of Retinal Disease

    PubMed Central

    Capozzi, Megan E.; Gordon, Andrew Y.; Penn, John S.

    2013-01-01

    Abstract Imaging of the eye plays an important role in ocular therapeutic discovery and evaluation in preclinical models and patients. Advances in ophthalmic imaging instrumentation have enabled visualization of the retina at an unprecedented resolution. These developments have contributed toward early detection of the disease, monitoring of disease progression, and assessment of the therapeutic response. These powerful technologies are being further harnessed for clinical applications by configuring instrumentation to detect disease biomarkers in the retina. These biomarkers can be detected either by measuring the intrinsic imaging contrast in tissue, or by the engineering of targeted injectable contrast agents for imaging of the retina at the cellular and molecular level. Such approaches have promise in providing a window on dynamic disease processes in the retina such as inflammation and apoptosis, enabling translation of biomarkers identified in preclinical and clinical studies into useful diagnostic targets. We discuss recently reported and emerging imaging strategies for visualizing diverse cell types and molecular mediators of the retina in vivo during health and disease, and the potential for clinical translation of these approaches. PMID:23421501

  15. 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 ...

  16. Generalized Degenerative Joint Disease in Osteoprotegerin (Opg) Null Mutant Mice.

    PubMed

    Bolon, B; Grisanti, M; Villasenor, K; Morony, S; Feige, U; Simonet, W S

    2015-09-01

    Bone structure is modulated by the interaction between receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor for RANKL, modifies osteoclast-mediated bone resorption directly and spares articular cartilage indirectly in rodents with immune-mediated arthritis by preventing subchondral bone destruction. The OPG/RANKL balance also seems to be critical in maintaining joint integrity in osteoarthritis, a condition featuring articular bone and cartilage damage in the absence of profound inflammation. The current study explored the role of OPG in sparing articular cartilage by evaluating joint lesions in adult C57BL/6J mice lacking osteoprotegerin (Opg (-) (/-)). At 3, 5, 7, 9, and 12 months of age, both sexes of Opg (-) (/-) mice developed severe degenerative joint disease (DJD) characterized by progressive loss of cartilage matrix and eventually articular cartilage. Lesions developed earlier and more severely in Opg (-) (/-) mice relative to age-matched, wild-type (Opg (+) (/+)), or heterozygous (Opg (+) (/-)) littermates (P ≤ .05). The femorotibial joint was affected bilaterally at 3 months, while other key weight-bearing diarthrodial joints (eg, coxofemoral, scapulohumeral, humeroradioulnar) were affected later and unilaterally. Cortical bone in subchondral plates and long bone diaphyses of Opg (-) (/-) mice but not Opg (+/+) or Opg (+) (/-) animals was osteoporotic by 3 months of age (P ≤ .05); the extent of porosity was less than the degree of DJD. Closure of the physes in long bones (P ≤ .05) and cartilage retention in the femoral primary spongiosa (P ≤ .05) affected chiefly Opg (-) (/-) mice. These data suggest that OPG plays an essential direct role in maintaining cartilage integrity in the articular surfaces and physes.

  17. [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

  18. The role of glial cells and the complement system in retinal diseases and Alzheimer's disease: common neural degeneration mechanisms.

    PubMed

    Harvey, Hannah; Durant, Szonya

    2014-11-01

    Many age-related degenerative diseases of the central nervous system (CNS) increasingly appear to have similarities in their underlying causes. By applying knowledge between disorders, and in particular between degenerative diseases of different components of the CNS (e.g. the eye and the brain), we can begin to elucidate general mechanisms of neural degeneration. Age-related macular degeneration and glaucoma, two diseases of retinal neurons, which have recently been discussed in view of their common mechanisms with Alzheimer's disease, highlight this perspective. This review discusses the common roles of the complement system (an immunological system) and glial cells (providing, amongst other functions, trophic support to neurons) in these three disorders. A number of facets of these systems would seem to be involved in the mechanisms of degeneration in at least two of the three diseases considered here. Regulatory proteins of the complement system (such as factor H), neurotrophin levels, and the interaction of microglia with the complement system in particular may be general to all three presentations of neural degeneration. Investigating the functioning of these fundamental systems across different diseases exemplifies the importance of considering advances in knowledge across a wider base than specific disease pathology. This may give insights both for understanding the function of these supporting systems and providing an avenue for developing future therapeutic targets general to neural degenerative diseases.

  19. Concise review: toward stem cell-based therapies for retinal neurodegenerative diseases.

    PubMed

    Bull, Natalie D; Martin, Keith R

    2011-08-01

    Loss of sight due to irreversible retinal neurodegeneration imposes a significant disease burden on both patients and society. Glaucoma and age-related macular degeneration are the commonest neurodegenerative blinding diseases in the developed world, and both are becoming increasingly prevalent as populations age. Our heavy reliance on our sense of sight means that visual loss often severely restricts day-to-day life, making it difficult to function without additional support. Visual impairment also limits employment possibilities, adding to the economic burden. Current therapies for many degenerative retinopathies are limited in their efficacy, often treating the effects of disease rather than the underlying causes. Consequently, the development of novel adjunctive neuroprotective and neuroregenerative treatments are important goals. Evidence from animal models suggests that stem cells could be useful as part of novel new treatment strategies for eye disease. The accessibility of the eye and extensive repertoire of available surgical techniques may facilitate the translation of stem cell-based therapies, for example, via transplantation, to the retina more rapidly than to other parts of the central nervous system. This concise review will examine how cell therapies are being applied experimentally for neuroregenerative and neuroprotective treatment of currently incurable degenerative retinal diseases. Furthermore, recent progress toward clinical translation of such therapies will be highlighted.

  20. 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.

  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. 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

  3. 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

  4. 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

  5. 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.

  6. Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

    PubMed Central

    2016-01-01

    Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described. PMID:27721914

  7. Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease

    PubMed Central

    Scoles, Drew; Higgins, Brian P.; Cooper, Robert F.; Dubis, Adam M.; Summerfelt, Phyllis; Weinberg, David V.; Kim, Judy E.; Stepien, Kimberly E.; Carroll, Joseph; Dubra, Alfredo

    2014-01-01

    Purpose. We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO). Methods. Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison. Results. Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart. Conclusions. Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further. PMID:24894394

  8. 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

  9. 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

  10. No publication bias in industry funded clinical trials of degenerative diseases of the spine.

    PubMed

    Son, Colin; Tavakoli, Samon; Bartanusz, Viktor

    2016-03-01

    Industry sponsorship of clinical research of degenerative diseases of the spine has been associated with excessive positive published results as compared to research carried out without industry funding. We sought the rates of publication of clinical trials of degenerative diseases of the spine based on funding source as a possible explanation for this phenomenon. We reviewed all clinical trials registered at clinicaltrials.gov relating to degenerative diseases of the spine as categorized under six medical subject heading terms (spinal stenosis, spondylolisthesis, spondylolysis, spondylosis, failed back surgery syndrome, intervertebral disc degeneration) and with statuses of completed or terminated. These collected studies were categorized as having, or not having, industry funding. Published results for these studies were then sought within the clinicaltrials.gov database itself, PubMed and Google Scholar. One hundred sixty-one clinical trials met these criteria. One hundred nineteen of these trials had industry funding and 42 did not. Of those with industry funding, 45 (37.8%) had identifiable results. Of those without industry funding, 17 (40.5%) had identifiable results. There was no difference in the rates of publication of results from clinical trials of degenerative diseases of the spine no matter the funding source.

  11. Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases

    PubMed Central

    2016-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway.

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

    ClinicalTrials.gov

    2016-10-13

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

  13. 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

  14. Vitreous Mediators in Retinal Hypoxic Diseases

    PubMed Central

    dell'Omo, Roberto; Semeraro, Francesco; Bamonte, Giulio; Cifariello, Francesco; Romano, Mario R.; Costagliola, Ciro

    2013-01-01

    The causes of retinal hypoxia are many and varied. Under hypoxic conditions, a variety of soluble factors are secreted into the vitreous cavity including growth factors, cytokines, and chemokines. Cytokines, which usually serve as signals between neighboring cells, are involved in essentially every important biological process, including cell proliferation, inflammation, immunity, migration, fibrosis, tissue repair, and angiogenesis. Cytokines and chemokines are multifunctional mediators that can direct the recruitment of leukocytes to sites of inflammation, promote the process, enhance immune responses, and promote stem cell survival, development, and homeostasis. The modern particle-based flow cytometric analysis is more direct, stable and sensitive than the colorimetric readout of the conventional ELISA but, similar to ELISA, is influenced by vitreous hemorrhage, disruption of the blood-retina barrier, and high serum levels of a specific protein. Finding patterns in the expression of inflammatory cytokines specific to a particular disease can substantially contribute to the understanding of its basic mechanism and to the development of a targeted therapy. PMID:23365490

  15. 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,…

  16. 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

  17. Molecular pathogenesis of retinal and choroidal vascular diseases.

    PubMed

    Campochiaro, Peter A

    2015-11-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch's membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch's membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for VEGF

  18. Thermolabile MTHFR genotype and retinal vascular occlusive disease

    PubMed Central

    Cahill, M; Karabatzaki, M; Donoghue, C; Meleady, R; Mynett-Johnson, L; Mooney, D; Graham, I; Whitehead, A; Shields, D

    2001-01-01

    BACKGROUND—Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined.
METHODS—A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined.
RESULTS—87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients.
CONCLUSIONS—The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

 PMID:11133719

  19. [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

  20. 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

  1. Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative disease.

    PubMed

    Colangeli, S; Barbanti Brodàno, G; Gasbarrini, A; Bandiera, S; Mesfin, A; Griffoni, C; Boriani, S

    2015-06-01

    Pedicle screw and rod instrumentation has become the preferred technique for performing stabilization and fusion in the surgical treatment of lumbar spine degenerative disease. Rigid fixation leads to high fusion rates but may also contribute to stress shielding and adjacent segment degeneration. Thus, the use of semirigid rods made of polyetheretherketone (PEEK) has been proposed. Although the PEEK rods biomechanical properties, such as anterior load sharing properties, have been shown, there are few clinical studies evaluating their application in the lumbar spine surgical treatment. This study examined a retrospective cohort of patients who underwent posterior lumbar fusion for degenerative disease using PEEK rods, in order to evaluate the clinical and radiological outcomes and the incidence of complications.

  2. Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative disease.

    PubMed

    Colangeli, S; Barbanti Brodàno, G; Gasbarrini, A; Bandiera, S; Mesfin, A; Griffoni, C; Boriani, S

    2015-06-01

    Pedicle screw and rod instrumentation has become the preferred technique for performing stabilization and fusion in the surgical treatment of lumbar spine degenerative disease. Rigid fixation leads to high fusion rates but may also contribute to stress shielding and adjacent segment degeneration. Thus, the use of semirigid rods made of polyetheretherketone (PEEK) has been proposed. Although the PEEK rods biomechanical properties, such as anterior load sharing properties, have been shown, there are few clinical studies evaluating their application in the lumbar spine surgical treatment. This study examined a retrospective cohort of patients who underwent posterior lumbar fusion for degenerative disease using PEEK rods, in order to evaluate the clinical and radiological outcomes and the incidence of complications. PMID:25751575

  3. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    PubMed

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    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 multi-modal 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.

  4. A Survey of Vitamin D Status in Patients with Degenerative Diseases of the Spine

    PubMed Central

    Zolfaghari, Farid; Faridmoayer, Alireza; Soleymani, Bahram; Mahabadi, Maryam

    2016-01-01

    Study Design Descriptive cross-sectional study. Purpose To determine the prevalence of vitamin D deficiency in patients with degenerative diseases of the spine about to undergo spinal surgery and the relations between such deficiency and potential risk factors. Overview of Literature Vitamin D has a major role in musculoskeletal system health maintenance. Recently, studies on degenerative diseases of the spine have shown a high prevalence of vitamin D deficiency in patients undergoing spine surgery. Methods Serum levels of 25(OH)D were determined by an electrochemiluminescence detection assay. The other variables were determined through relevant questionnaires, and the data was analyzed through analysis of variance, t-test, chi-square and multivariate logistic regression analysis. Results A total of 110 patients were enrolled in the study. The mean serum level of 25(OH)D was 27.45±18.75 ng/mL, and 44.5% of patients showed vitamin D deficiency (25(OH)D<20 ng/mL), with an additional 17.3% of patients having a serum level of 25(OH)D that was insufficient (20≤25(OH)D<30 ng/mL). The prevalence of vitamin D deficiency was significantly higher in the younger age group compared to the older age group (p<0.001) and the ones without a history of taking vitamin D supplements (p=0.013). Compared to men, women showed significantly higher levels of vitamin D (p=0.029). Conclusions A high prevalence of vitamin D deficiency is seen in patients with degenerative diseases of the spine. On the other hand, the conventional risk factors such as old age or female sex alone did not seem to be sufficient in determining the likelihood of deficiency. Thus, it is recommended that vitamin D deficiency prevention strategies comprise a broader spectrum of the population through which such degenerative diseases and their consequences may be prevented or delayed. PMID:27790310

  5. Retinal emboli and cardiovascular disease: the Beaver Dam Eye Study.

    PubMed Central

    Klein, Ronald; Klein, Barbara E K; Moss, Scot E; Meuer, Stacy M

    2003-01-01

    PURPOSE: To describe the 10-year incidence of retinal emboli, the associated risk factors, and the relationship of retinal emboli to stroke and ischemic heart disease mortality. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population-based study of persons 43 to 86 years of age. Retinal emboli were detected at baseline (1988-1990) and at a 5-year (1993-1995) and a 10-year (1998-2000) follow-up by grading of stereoscopic 30 degrees color fundus photographs using standardized protocols. Cause-specific mortality was determined from death certificates. RESULTS: The 10-year cumulative incidence of retinal emboli was 1.5%. While adjusting for age and sex, the incidence of retinal emboli was associated with increased pulse pressure (odds ratio [OR] 4th versus 1st quartile range, 2.42; 95% confidence interval (CI), 0.98-5.97; P test of trend = .03), higher serum total cholesterol (OR, 2.77; 95% CI, 1.06-7.23; P = .03), higher leukocyte count (OR, 2.28; 95% CI, 1.04-4.96; P = .05), smoking status (OR current versus never smoker, 4.60: 95% CI, 2.08-10.16; P < .001), and a history of coronary artery bypass surgery (OR, 7.17; 95% CI, 3.18-16.18; P < .001) at baseline. While controlling for age, sex, and systemic factors, a significantly higher hazard of dying with a mention of stroke on the death certificate was found in people with retinal emboli (hazard ratio, 2.40; 95% CI, 1.16-4.99) compared with those without. CONCLUSIONS: The data show an association of smoking and cardiovascular disease with the incidence of retinal emboli. Also, persons with retinal emboli are at increased risk of stroke-related death. PMID:14971575

  6. Advances in Susceptibility Genetics of Intervertebral Degenerative Disc Disease

    PubMed Central

    Zhang, Yin'gang; Sun, Zhengming; Liu, Jiangtao; Guo, Xiong

    2008-01-01

    The traditional view that the etiology of lumbar disc herniation is primarily due to age, gender, occupation, smoking and exposure to vehicular vibration dominated much of the last century. Recent research indicates that heredity may be largely responsible for the degeneration as well as herniation of intervertebral discs. Since 1998, genetic influences have been confirmed by the identification of several genes forms associated with disc degeneration. These researches are paving the way for a better understanding of the biologic mechanisms. Now, many researchers unanimously agree that lumbar disc herniation appears to be similar to other complex diseases, whose etiology has both environmental and hereditary influence, each with a part of contribution and relative risk. Then addressing the etiological of lumbar disc herniation, it is important to integrate heredity with the environment factors. For the purpose of this review, we have limited our discussion to several susceptibility genes associated with disc degeneration. PMID:18781226

  7. Inter- and intraobserver reliability in radiographic assessment of degenerative disk disease.

    PubMed

    Zook, Jason; Djurasovic, Mladen; Crawford, Charles; Bratcher, Kelly; Glassman, Steven; Carreon, Leah

    2011-04-11

    Clinicians use descriptive classification systems when treating patients with low back pain as an adjunct to surgical decision making. Magnetic resonance imaging (MRI) changes, including Modic changes, the presence of a high-intensity zone, and internal disk desiccation, are commonly used descriptors. The question remains whether different clinicians interpret these terms similarly. This study evaluated the inter- and intraobserver reliability of commonly used MRI classifications in patients presenting with low back pain.Sixty-six patients who underwent lumbar spine fusion surgery at a single multiphysician spine specialty practice for degenerative disk disease were identified. For each surgical level, the following MRI variables were determined independently by 3 fellowship-trained spine surgeons: presence or absence of high-intensity zone and/or internal disk desiccation, presence and classification of disk herniation, Modic grade, and disk height. Each surgeon reviewed the same set of MRI studies a second time at least 2 weeks from the first reading. Inter- and intraobserver reliability was determined using multiobserver Kappa coefficients. Intraobserver reliability ranged from 0.563 to 0.988, with greatest agreement in determining disk height. The greatest interobserver agreement was for determining Modic changes (0.819).Controversy remains on the criteria for diagnosing degenerative disk disease. In patients presenting with low back pain diagnosed with degenerative disk disease, the inter- and intraobserver reliability with use of several common MRI diagnostic tools was substantial. These data imply that clinicians interpret these findings in a reproducible fashion and interpret these terms similarly.

  8. The molecular basis of human retinal and vitreoretinal diseases.

    PubMed

    Berger, Wolfgang; Kloeckener-Gruissem, Barbara; Neidhardt, John

    2010-09-01

    During the last two to three decades, a large body of work has revealed the molecular basis of many human disorders, including retinal and vitreoretinal degenerations and dysfunctions. Although belonging to the group of orphan diseases, they affect probably more than two million people worldwide. Most excitingly, treatment of a particular form of congenital retinal degeneration is now possible. A major advantage for treatment is the unique structure and accessibility of the eye and its different components, including the vitreous and retina. Knowledge of the many different eye diseases affecting retinal structure and function (night and colour blindness, retinitis pigmentosa, cone and cone rod dystrophies, photoreceptor dysfunctions, as well as vitreoretinal traits) is critical for future therapeutic development. We have attempted to present a comprehensive picture of these disorders, including biological, clinical, genetic and molecular information. The structural organization of the review leads the reader through non-syndromic and syndromic forms of (i) rod dominated diseases, (ii) cone dominated diseases, (iii) generalized retinal degenerations and (iv) vitreoretinal disorders, caused by mutations in more than 165 genes. Clinical variability and genetic heterogeneity have an important impact on genetic testing and counselling of affected families. As phenotypes do not always correlate with the respective genotypes, it is of utmost importance that clinicians, geneticists, counsellors, diagnostic laboratories and basic researchers understand the relationships between phenotypic manifestations and specific genes, as well as mutations and pathophysiologic mechanisms. We discuss future perspectives. PMID:20362068

  9. Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases.

    PubMed

    Loperfido, Mariana; Steele-Stallard, Heather B; Tedesco, Francesco Saverio; VandenDriessche, Thierry

    2015-01-01

    Human pluripotent stem cells represent a unique source for cell-based therapies and regenerative medicine. The intrinsic features of these cells such as their easy accessibility and their capacity to be expanded indefinitely overcome some limitations of conventional adult stem cells. Furthermore, the possibility to derive patient-specific induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization. Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials for skeletal muscle disorders.

  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. Retinal remodeling in human retinitis pigmentosa.

    PubMed

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies. PMID:27020758

  12. 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.

  13. 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…

  14. Imaging of degenerative spine disease--the state of the art.

    PubMed

    Sasiadek, Marek J; Bladowska, Joanna

    2012-01-01

    The authors review the current state of imaging of degenerative spinal disease (DSD), which is one of the most common disorders in humans. The most important definitions as well as short descriptions of the etiopathology and clinical presentation of DSD are provided first, followed by an overview of conventional and advanced imaging methods that are used in DSD. The authors then discuss in detail the imaging patterns of particular types of degenerative changes. Finally, the current imaging algorithm in DSD is presented. The imaging method of choice is magnetic resonance, including advanced techniques--especially diffusion tensor imaging. Other imaging methods (plain radiography, computed tomography, vascular studies, scintigraphy, positron emission tomography, discography) play a supplementary role ).

  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. 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

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

    PubMed

    Brand, C S

    2012-04-01

    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.

  18. Nerve cell death in degenerative diseases of the central nervous system: clinical aspects.

    PubMed

    Agid, Y; Blin, J

    1987-01-01

    The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms. PMID:3556087

  19. 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

  20. The domestic cat as a large animal model for characterization of disease and therapeutic intervention in hereditary retinal blindness.

    PubMed

    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.

  1. Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings

    PubMed Central

    Saleem, Shafaq; Rehmani, Muhammad Asim Khan; Raees, Aisha; Alvi, Arsalan Ahmad; Ashraf, Junaid

    2013-01-01

    Study Design Cross sectional and observational. Purpose To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. Overview of Literature Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. Methods This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. Results During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). Conclusions Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life. PMID:24353850

  2. Corticosteroid and hyaluronic acid treatments in equine degenerative joint disease. A review.

    PubMed

    Nizolek, D J; White, K K

    1981-10-01

    Degenerative arthrosis is perhaps the most common debilitating disease of performance horses. Treatment should be based upon a knowledge of the anatomy and physiology of normal joints and upon an understanding of the processes of degeneration and repair. These topics are briefly reviewed. Although rest is probably, the most beneficial therapy, physical and pharmaceutical treatments are often employed in an effort to speed recovery. The effects and relative benefits of intrasynovial injections of corticosteroids, hyaluronica cid, and Arteparon are considered in detail. Although local corticosteroid therapy is inexpensive and is effective in reducing lameness caused by degenerative joint disease, it is rarely indicated. Septic arthritis and "steroid arthropathy" are two serious sequelae. Whereas the incidence of the former may be avoided through careful technique, the latter effect is inherent in the action of the drug. The accelerated rate of joint destruction observed in steroid arthropathy is due to suppression of chondrocyte metabolism and thus the processes of cartilage maintenance and repair. Hyaluronic acid is present in the synovial fluid and within the matrix of cartilage. The commercial preparation is no approved for use in the United States, but it is commonly obtained from other countries. Although hyaluronate apparently does not function in the lubrication of cartilage surfaces, it may improve lubrication of soft tissues thus decreasing resistance to joint movement and lessening pain. Reports substantiate the effectiveness of hyaluronic acid in treating early cases of degenerative arthrosis despite the fact that the drug does not significantly promote cartilage healing. Arteparon, a polysulfated glycosaminoglycan, has been used in Europe for two decades in the treatment of degeneration joint disease and is currently being tested in this country. The drug is deposited within diseased cartilage and improves the functional properties of the cartilage as

  3. 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

  4. Analysis of Cervical Sagittal Balance Parameters in MRIs of Patients with Disc-Degenerative Disease

    PubMed Central

    Wang, Zhao-Lin; Xiao, Jian-Lin; Mou, Jian-Hui; Qin, Ting-Zheng; Liu, Peng

    2015-01-01

    Background The aim of this study was to explore the correlations between the different parameters of the cervical sagittal balance in magnetic resonance images (MRI) and evaluate the criteria for their clinical application in disc-degenerative diseases. Material/Methods We conducted a retrospective review of the MRIs of 125 adult outpatients with disc-degenerative diseases of the cervical spine; the images were obtained between May and July 2014 at our institute. The control group comprised 50 volunteers whose MRIs were also obtained. The parameters measured in the MRIs were: neck tilt (NT), T1 slope (T1S), thoracic inlet angle (TIA), and Cobb’s angle (C2–7). The correlation between the various parameters was analyzed using the Pearson correlation coefficient. Results The outpatients group showed moderate correlation between TIA and T1S, a significant correlation between TIA and NT, a weak correlation between T1S and Cobb’s angle, and a weakly negative correlation between T1S and NT. Further, the TIA showed no significant difference between the outpatient group and the control group, as per the sample t test. Conclusions Our findings indicate that TIA, T1S, and NT could be used as indices for the evaluation of cervical sagittal balance and that the TIA could be used as a reference to assess the cervical compensation. Restoration of the NT and T1S should be considered as a goal of surgical treatment during the preoperative planning in patients with disc-degenerative diseases. PMID:26486162

  5. 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

  6. 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

  7. Computer aided diagnosis of degenerative intervertebral disc diseases from lumbar MR images.

    PubMed

    Oktay, Ayse Betul; Albayrak, Nur Banu; Akgul, Yusuf Sinan

    2014-10-01

    This paper presents a novel method for the automated diagnosis of the degenerative intervertebral disc disease in midsagittal MR images. The approach is based on combining distinct disc features under a machine learning framework. The discs in the lumbar MR images are first localized and segmented. Then, intensity, shape, context, and texture features of the discs are extracted with various techniques. A Support Vector Machine classifier is applied to classify the discs as normal or degenerated. The method is tested and validated on a clinical lumbar spine dataset containing 102 subjects and the results are comparable to the state of the art.

  8. [Algorithm of the diagnostics of trauma and degenerative diseases of the spine].

    PubMed

    Shchedrenok, V V; Sebelev, K I; Anikeev, N V; Tiul'kin, O N; Kaurova, T A; Moguchaia, O V

    2011-01-01

    Clinico-radial data were compared in 583 patients with trauma and degenerative diseases of the spine. The clinico-diagnostic complex included radiography of the spine (round-up and functional), magnetic resonance imaging, computerized helical tomography of the spine with spondylometric measurements. Indices of the measurements of the cross-section area of the vertebral artery canal at the level of C3-C6 vertebrae and the volume of the intervertebral canal at different levels in health among men and women are presented. An algorithm of radiation diagnostics in pathology of the spine is proposed.

  9. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    PubMed

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  10. Novel roles for α-crystallins in retinal function and disease

    PubMed Central

    Kannan, Ram; Sreekumar, Parameswaran G.; Hinton, David R.

    2012-01-01

    α-Crystallins are key members of the superfamily of small heat shock proteins that have been studied in detail in the ocular lens. Recently, novel functions for α-crystallins have been identified in the retina and in the retinal pigmented epithelium (RPE). αB-Crystallin has been localized to multiple compartments and organelles including mitochondria, golgi apparatus, endoplasmic reticulum and nucleus. α-Crystallins are regulated by oxidative and endoplasmic reticulum stress, and inhibit apoptosis-induced cell death. α-Crystallins interact with a large number of proteins that include other crystallins, and apoptotic, cytoskeletal, inflammatory, signaling, angiogenic, and growth factor molecules. Studies with RPE from αB-crystallin deficient mice have shown that αB-crystallin supports retinal and choroidal angiogenesis through its interaction with vascular endothelial growth factor. αB-Crystallin has also been shown to have novel functions in the extracellular space. In RPE, αB-crystallin is released from the apical surface in exosomes where it accumulates in the interphotoreceptor matrix and may function to protect neighboring cells. In other systems administration of exogenous recombinant αB-crystallin has been shown to be anti-inflammatory. Another newly described function of αB-crystallin is its ability to inhibit β-amyloid fibril formation. α-Crystallin mini-chaperone peptides have been identified that elicit anti-apoptotic function in addition to being efficient chaperones. Generation of liposomal particles and other modes of nanoencapsulation of these minipeptides could offer great therapeutic advantage in ocular delivery for a wide variety of retinal degenerative, inflammatory and vascular diseases including age related macular degeneration and diabetic retinopathy. PMID:22721717

  11. Echocardiographic Follow-up of Robotic Mitral Valve Repair for Mitral Regurgitation due to Degenerative Disease

    PubMed Central

    Wang, Yao; Gao, Chang-Qing; Shen, Yan-Song; Wang, Gang

    2016-01-01

    Background: Mitral valve (MV) repair can now be carried out through small incisions with the use of robotic assistance. Previous reports have demonstrated the excellent clinical result of robotic MV repair for degenerative mitral regurgitation (MR). However, there has been limited information regarding the echocardiographic follow-up of these patients. The present study was therefore to evaluate the echocardiographic follow-up outcomes after robotic MV repair in patients with MR due to degenerative disease of the MV. Methods: A retrospective analysis was undertaken using data from the echocardiographic database of our department. Between March 2007 and February 2015, 84 patients with degenerative MR underwent robotic MV repair. The repair techniques included leaflet resection in 67 patients (79.8%), artificial chordae in 20 (23.8%), and ring annuloplasty in 79 (94.1%). Eighty-one (96.4%) of the 84 patients were eligible for echocardiographic follow-up assessment, and no patients were lost to follow-up. Results: At a median echocardiographic follow-up of 36.0 months (interquartile range 14.3–59.4 months), four patients (4.9%) developed recurrent mild MR, and no patients had more than mild MR. Mean MR grade, left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) were significantly decreased when compared with preoperative values. Mean MR grade decreased from 3.96 ± 0.13 to 0.17 ± 0.49 (Z = −8.456, P < 0.001), LAD from 43.8 ± 5.9 to 35.5 ± 3.8 mm (t = 15.131, P < 0.001), LVEDD from 51.0 ± 5.0 to 43.3 ± 2.2 mm (t = 14.481, P < 0.001), and LVEF from 67.3 ± 7.0% to 63.9 ± 5.1% (t = 4.585, P < 0.001). Conclusion: Robotic MV repair for MR due to degenerative disease is associated with a low rate of recurrent MR, and a significant improvement in MR grade, LAD, and LVEDD, but a significant decrease in LVEF at echocardiographic follow-up. PMID:27625092

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

    PubMed

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

    2015-08-01

    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.

  13. 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.

  14. Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

    PubMed

    Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

    2012-01-01

    Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

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

    PubMed

    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

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

    PubMed

    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.

  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. 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.

  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. Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for Degenerative Disc Disease

    PubMed Central

    Sivakamasundari, V; Lufkin, Thomas

    2013-01-01

    The intervertebral disc (IVD) is immensely important for the integrity of vertebral column function. The highly specialized IVD functions to confer flexibility and tensile strength to the spine and endures various types of biomechanical force. Degenerative disc disease (DDD) is a prevalent musculoskeletal disorder and is the major cause of low back pain and includes the more severe degenerative lumbar scoliosis, disc herniation and spinal stenosis. DDD is a multifactorial disorder whereby an imbalance of anabolic and catabolic factors, or alterations to cellular composition, or biophysical stimuli and genetic background can all play a role in its genesis. However, our comprehension of IVD formation and theetiology of disc degeneration (DD) are far from being complete, hampering efforts to formulate appropriate therapies to tackle DD. Knowledge of the stem cells and various techniques to manipulate and direct them to particular fates have been promising in adopting a stem-cell based regenerative approach to DD. Moreover, new evidence on the residence of stem/progenitor cells within particular IVD niches has emerged holding promise for future therapeutic applications. Existing issues pertaining to current therapeutic approaches are also covered in this review. PMID:23951558

  1. 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

  2. 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.

  3. 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

  4. Visuo-proprioceptive interactions in degenerative cervical spine diseases requiring surgery.

    PubMed

    Freppel, S; Bisdorff, A; Colnat-Coulbois, S; Ceyte, H; Cian, C; Gauchard, G; Auque, J; Perrin, P

    2013-01-01

    Cervical proprioception plays a key role in postural control, but its specific contribution is controversial. Postural impairment was shown in whiplash injuries without demonstrating the sole involvement of the cervical spine. The consequences of degenerative cervical spine diseases are underreported in posture-related scientific literature in spite of their high prevalence. No report has focused on the two different mechanisms underlying cervicobrachial pain: herniated discs and spondylosis. This study aimed to evaluate postural control of two groups of patients with degenerative cervical spine diseases with or without optokinetic stimulation before and after surgical treatment. Seventeen patients with radiculopathy were recruited and divided into two groups according to the spondylotic or discal origin of the nerve compression. All patients and a control population of 31 healthy individuals underwent a static posturographic test with 12 recordings; the first four recordings with the head in 0° position: eyes closed, eyes open without optokinetic stimulation, with clockwise and counter clockwise optokinetic stimulations. These four sensorial situations were repeated with the head rotated 30° to the left and to the right. Patients repeated these 12 recordings 6weeks postoperatively. None of the patients reported vertigo or balance disorders before or after surgery. Prior to surgery, in the eyes closed condition, the herniated disc group was more stable than the spondylosis group. After surgery, the contribution of visual input to postural control in a dynamic visual environment was reduced in both cervical spine diseases whereas in a stable visual environment visual contribution was reduced only in the spondylosis group. The relative importance of visual and proprioceptive inputs to postural control varies according to the type of pathology and surgery tends to reduce visual contribution mostly in the spondylosis group.

  5. Modifier genes as therapeutics: the nuclear hormone receptor Rev Erb alpha (Nr1d1) rescues Nr2e3 associated retinal disease.

    PubMed

    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.

  6. 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.

  7. Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling.

    PubMed

    Bales, Katie L; Gross, Alecia K

    2016-09-01

    Retinal trafficking proteins are involved in molecular assemblies that govern protein transport, orchestrate cellular events involved in cilia formation, regulate signal transduction, autophagy and endocytic trafficking, all of which if not properly controlled initiate retinal degeneration. Improper function and or trafficking of these proteins and molecular networks they are involved in cause a detrimental cascade of neural retinal remodeling due to cell death, resulting as devastating blinding diseases. A universal finding in retinal degenerative diseases is the profound detection of retinal remodeling, occurring as a phased modification of neural retinal function and structure, which begins at the molecular level. Retinal remodeling instigated by aberrant trafficking of proteins encompasses many forms of retinal degenerations, such as the diverse forms of retinitis pigmentosa (RP) and disorders that resemble RP through mutations in the rhodopsin gene, retinal ciliopathies, and some forms of glaucoma and age-related macular degeneration (AMD). As a large majority of genes associated with these different retinopathies are overlapping, it is imperative to understand their underlying molecular mechanisms. This review will discuss some of the most recent discoveries in vertebrate retinal remodeling and retinal degenerations caused by protein mistrafficking. PMID:26632497

  8. Management of degenerative lumbosacral disease in cats by dorsal laminectomy and lumbosacral stabilization.

    PubMed

    Danielski, A; Bertran, J; Fitzpatrick, N

    2013-01-01

    In this case series we describe the diagnosis and surgical treatment of five cats affected by clinical cauda equina syndrome as a result of degenerative lumbosacral stenosis. Radiographic and magnetic resonance imaging findings confirmed the suspected diagnosis of disc-associated lumbosacral disease. Cauda equina decompression was achieved by dorsal laminectomy followed by dorsal annulectomy and nuclear extirpation. Dorsal stabilization was achieved using miniature positive-profile pins inserted into the vertebral body of L7 and the wings of S1 with the free ends of the pins being embedded in a bolus of gentamicin-impregnated polymethylmethacrylate. Reassessment two years postoperatively using a previously validated feline specific owner questionnaire indicated satisfactory outcome with complete return to normal activity and resolution of signs of pain in all cases.

  9. 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.

  10. 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

  11. 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

  12. Complement Activation and Inhibition in Retinal Diseases.

    PubMed

    Kleinman, Mark E; Ambati, Jayakrishna

    2016-01-01

    Within the past several decades, a brigade of dedicated researchers from around the world has provided essential insights into the critical niche of immune-mediated inflammation in the pathogenesis of age-related macular degeneration (AMD). Yet, the question has lingered as to whether disease-initiating events are more or less dependent on isolated immune-related responses, unimpeded inflammation, endogenous pathways of age-related cell senescence and oxidative stress, or any of the other numerous molecular derangements that have been identified in the natural history of AMD. There is now an abundant cache of data signifying immune system activation as an impetus in the pathogenesis of this devastating condition. Furthermore, recent rigorous investigations have revealed multiple inciting factors, including several important complement-activating components, thus creating a new array of disease-modulating targets for the research and development of molecular therapeutic interventions. While the precise in vivo effects of complement activation and inhibition in the progression and treatment of AMD remain to be determined, ongoing clinical trials of the first generation of complement-targeted therapeutics are hoped to yield critical data on the contribution of this pathway to the disease process. PMID:26501209

  13. 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

  14. Diagnosis and treatment of degenerative joint disease in a captive male chimpanzee (Pan troglodytes).

    PubMed

    Videan, Elaine N; Lammey, Michael L; Lee, D Rick

    2011-03-01

    Degenerative joint disease (DJD), also known as osteoarthritis, has been well documented in aging populations of captive and free-ranging macaques; however, successful treatments for DJD in nonhuman primates have not been published. Published data on chimpanzees show little to no DJD present in the wild, and there are no published reports of DJD in captive chimpanzees. We report here the first documented case of DJD of both the right and left femorotibial joints in a captive male chimpanzee. Progression from minimal to moderate to severe osteoarthritis occurred in this animal over the course of 1 y. Treatment with chondroprotective supplements (that is, glucosamine chondroitin, polysulfated glycosaminoglycan) and intraarticular corticosteroid injections (that is, methylprednisolone, ketorolac), together with pain management (that is, celecoxib, tramadol, carprofen), resulted in increased activity levels and decreased clinical signs of disease. DJD has a considerable negative effect on quality of life among the human geriatric population and therefore is likely to be one of the most significant diseases that will affect the increasingly aged captive chimpanzee population. As this case study demonstrates, appropriate treatment can improve and extend quality of life dramatically in these animals. However, in cases of severe osteoarthritis cases, medication alone may be insufficient to increase stability, and surgical options should be explored. PMID:21439223

  15. Diagnosis and Treatment of Degenerative Joint Disease in a Captive Male Chimpanzee (Pan troglodytes)

    PubMed Central

    Videan, Elaine N; Lammey, Michael L; Lee, D Rick

    2011-01-01

    Degenerative joint disease (DJD), also known as osteoarthritis, has been well documented in aging populations of captive and free-ranging macaques; however, successful treatments for DJD in nonhuman primates have not been published. Published data on chimpanzees show little to no DJD present in the wild, and there are no published reports of DJD in captive chimpanzees. We report here the first documented case of DJD of both the right and left femorotibial joints in a captive male chimpanzee. Progression from minimal to moderate to severe osteoarthritis occurred in this animal over the course of 1 y. Treatment with chondroprotective supplements (that is, glucosamine chondroitin, polysulfated glycosaminoglycan) and intraarticular corticosteroid injections (that is, methylprednisolone, ketorolac), together with pain management (that is, celecoxib, tramadol, carprofen), resulted in increased activity levels and decreased clinical signs of disease. DJD has a considerable negative effect on quality of life among the human geriatric population and therefore is likely to be one of the most significant diseases that will affect the increasingly aged captive chimpanzee population. As this case study demonstrates, appropriate treatment can improve and extend quality of life dramatically in these animals. However, in cases of severe osteoarthritis cases, medication alone may be insufficient to increase stability, and surgical options should be explored. PMID:21439223

  16. Nonsteroidal Anti-Inflammatory Drugs for Retinal Disease

    PubMed Central

    Schoenberger, Scott D.; Kim, Stephen J.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease. PMID:23365785

  17. [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.

  18. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    PubMed

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  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. The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo

    PubMed Central

    Rao, Kollu N.; Anand, Manisha; Khanna, Hemant

    2016-01-01

    ABSTRACT Mutations in RPGRORF15 (retinitis pigmentosa GTPase regulator) are a major cause of inherited retinal degenerative diseases. RPGRORF15 (1152 residues) is a ciliary protein involved in regulating the composition and function of photoreceptor cilia. The mutational hotspot in RPGRORF15 is an unusual C-terminal domain encoded by exon ORF15, which is rich in polyglutamates and glycine residues (Glu-Gly domain) followed by a short stretch of basic amino acid residues (RPGRC2 domain; residues 1072-1152). However, the properties of the ORF15-encoded domain and its involvement in the pathogenesis of the disease are unclear. Here we show that RPGRORF15 is glutamylated at the C-terminus, as determined by binding to GT335, which recognizes glutamylated substrates. This reactivity is lost in two mouse mutants of Rpgr, which do not express RPGRORF15 due to disease-causing mutations in exon ORF15. Our results indicate that RPGRORF15 is posttranslationally glutamylated in the Glu-Gly domain and that the GT335 antibody predominantly recognizes RPGRORF15 in photoreceptor cilia. PMID:26941104

  1. National trends in outpatient surgical treatment of degenerative cervical spine disease.

    PubMed

    Baird, Evan O; Egorova, Natalia N; McAnany, Steven J; Qureshi, Sheeraz A; Hecht, Andrew C; Cho, Samuel K

    2014-08-01

    Study Design Retrospective population-based observational study. Objective To assess the growth of cervical spine surgery performed in an outpatient setting. Methods A retrospective study was conducted using the United States Healthcare Cost and Utilization Project's State Inpatient and Ambulatory Surgery Databases for California, New York, Florida, and Maryland from 2005 to 2009. Current Procedural Terminology, fourth revision (CPT-4) and International Classification of Diseases, ninth revision Clinical Modification (ICD-9-CM) codes were used to identify operations for degenerative cervical spine diseases in adults (age > 20 years). Disposition and complication rates were examined. Results There was an increase in cervical spine surgeries performed in an ambulatory setting during the study period. Anterior cervical diskectomy and fusion accounted for 68% of outpatient procedures; posterior decompression made up 21%. Younger patients predominantly underwent anterior fusion procedures, and patients in the eighth and ninth decades of life had more posterior decompressions. Charlson comorbidity index and complication rates were substantially lower for ambulatory cases when compared with inpatients. The majority (>99%) of patients were discharged home following ambulatory surgery. Conclusions Recently, the number of cervical spine surgeries has increased in general, and more of these procedures are being performed in an ambulatory setting. The majority (>99%) of patients are discharged home but the nature of analyzing administrative data limits accurate assessment of postoperative complications and thus patient safety. This increase in outpatient cervical spine surgery necessitates further discussion of its safety.

  2. Presentation of Complex Homozygous Allele in ABCA4 Gene in a Patient with Retinitis Pigmentosa.

    PubMed

    Audere, Māreta; Rutka, Katrīna; Šepetiene, Svetlana; Lāce, Baiba

    2015-01-01

    Retinitis pigmentosa is a degenerative retinal disease characterized by progressive photoreceptor damage, which causes loss of peripheral and night vision and the development of tunnel vision and may result in loss of central vision. This study describes a patient with retinitis pigmentosa caused by a mutation in the ABCA4 gene with complex allele c.1622T>C, p.L541P; c.3113C>T, p.A1038V in homozygous state. PMID:26229699

  3. 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.

  4. Induced pluripotent stem cell therapies for retinal disease

    PubMed Central

    Comyn, Oliver; Lee, Edward; MacLaren, Robert E

    2010-01-01

    Purpose of review: This review will discuss how recent advances with induced pluripotent stem (iPS) cells have brought the science of stem cell biology much closer to clinical application for patients with retinal degeneration. Recent findings: The ability to generate embryonic stem (ES) cells by reprogramming DNA taken from adult cells was demonstrated by the cloning of Dolly the sheep by somatic cell nuclear transfer over ten years ago. Recently it has been shown that adult cells can be reprogrammed directly, without the need for a surrogate oocyte through the generation of induced pluripotent stem (iPS) cells. The method of reprogramming has since been optimised to avoid the use of retroviruses, making the process considerably safer. Last year human iPS cells were isolated from an 80 year old patient with neurodegenerative disease and differentiated into neurons in vitro. Summary: For stem cell therapies, the retina has the optimal combination of ease of surgical access, combined with an ability to observe transplanted cells directly through the clear ocular media. The question now is which retinal diseases are most appropriate targets for clinical trials using iPS cell approaches. PMID:19949329

  5. 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

  6. Production of Retinal Cells from Confluent Human iPS Cells.

    PubMed

    Reichman, Sacha; Goureau, Olivier

    2016-01-01

    Human induced pluripotent stem (hiPS) cells could be used as an unlimited source of retinal cells for the treatment of retinal degenerative diseases. Although much progress has been made in the differentiation of pluripotent stem cells towards different retinal lineages, the production of retinal cells from hiPS cells for therapeutic approaches require the development of easy and standardized protocols. In this chapter, we describe a simple and effective protocol for retinal differentiation of hiPS cells bypassing embryoid body formation and the use of exogenous molecules and substrates. In 2 weeks, confluent hiPS cells cultured in pro-neural medium can generate both retinal pigmented epithelial cells and self-forming neural retina-like structures containing retinal progenitor cells. These progenitors can be differentiated into all retinal cell types, including retinal ganglion cells and precursors of photoreceptors, which could find important applications in regenerative medicine. This differentiation system and the resulting hiPS-derived retinal cells will also offer opportunity to study the molecular and cellular mechanisms underlying human retinal development, and the establishment of in vitro models of human retinal degenerative diseases. PMID:25417064

  7. Production of Retinal Cells from Confluent Human iPS Cells.

    PubMed

    Reichman, Sacha; Goureau, Olivier

    2016-01-01

    Human induced pluripotent stem (hiPS) cells could be used as an unlimited source of retinal cells for the treatment of retinal degenerative diseases. Although much progress has been made in the differentiation of pluripotent stem cells towards different retinal lineages, the production of retinal cells from hiPS cells for therapeutic approaches require the development of easy and standardized protocols. In this chapter, we describe a simple and effective protocol for retinal differentiation of hiPS cells bypassing embryoid body formation and the use of exogenous molecules and substrates. In 2 weeks, confluent hiPS cells cultured in pro-neural medium can generate both retinal pigmented epithelial cells and self-forming neural retina-like structures containing retinal progenitor cells. These progenitors can be differentiated into all retinal cell types, including retinal ganglion cells and precursors of photoreceptors, which could find important applications in regenerative medicine. This differentiation system and the resulting hiPS-derived retinal cells will also offer opportunity to study the molecular and cellular mechanisms underlying human retinal development, and the establishment of in vitro models of human retinal degenerative diseases.

  8. Role of Diffusion Tensor MR Imaging in Degenerative Cervical Spine Disease: a Review of the Literature.

    PubMed

    Banaszek, A; Bladowska, J; Podgórski, P; Sąsiadek, M J

    2016-09-01

    In the article we review the current role of diffusion tensor imaging (DTI), a modern magnetic resonance (MR) technique, in the diagnosis and the management of cervical spondylotic myelopathy (CSM), the most serious complication of degenerative cervical spine disease (DCSD). The pathogenesis of DCSD is presented first with an emphasis placed on the pathological processes leading to myelopathy development. An understanding of the pathophysiological background of DCSD is necessary for appropriate interpretation of MR images, both plain and DTI. Conventional MRI is currently the imaging modality of choice in DCSD and provides useful information concerning the extent of spondylotic changes and degree of central spinal canal stenosis; however its capability in myelopathy detection is limited. DTI is a state of the art imaging method which recently has emerged in spinal cord investigations and has the potential to detect microscopic alterations which are beyond the capability of plain MRI. In the article we present the physical principles underlying DTI which determine its sensitivity, followed by an overview of technical aspects of DTI acquisition with a special consideration of spinal cord imaging. Finally, the scientific reports concerning DTI utility in DSCD are also reviewed. DTI detects spinal cord injury in the course of DCSD earlier than any other method and could be useful in predicting surgical outcomes in CMS patients, however technical and methodology improvement as well as standardization of acquisition protocols and postprocessing methods among the imaging centers are needed before its implementation in clinical practice.

  9. Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease.

    PubMed Central

    Fässler, R; Schnegelsberg, P N; Dausman, J; Shinya, T; Muragaki, Y; McCarthy, M T; Olsen, B R; Jaenisch, R

    1994-01-01

    Type IX collagen is a nonfibrillar collagen composed of three gene products, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules are localized on the surface of type II-containing fibrils and consist of two arms, a long arm that is crosslinked to type II collagen and a short arm that projects into the perifibrillar space. In hyaline cartilage, the alpha 1(IX) collagen transcript encodes a polypeptide with a large N-terminal globular domain (NC4), whereas in many other tissues an alternative transcript encodes an alpha 1(IX) chain with a truncated NC4 domain. It has been proposed that type IX molecules are involved in the interaction of fibrils with each other or with other components of the extracellular matrix. To test this hypothesis, we have generated a mouse strain lacking both isoforms of the alpha 1(IX) chain. Homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis. Images PMID:8197187

  10. Gene Therapy for Retinal Disease: What Lies Ahead.

    PubMed

    MacLaren, Robert E

    2015-01-01

    Gene therapy in simple terms can be defined as a medical treatment that exerts its effects using molecules of DNA or RNA within cells. Most traditional drugs act by mechanisms that include binding to cell surface receptors, inhibiting enzymes in intracellular pathways or by modifying transcription. These approaches rely to some extent on a normal genetic make-up of the cell in the final common pathway, which raises significant challenges in diseases that are caused by specific gene mutations. An alternative gene therapy approach to change the behaviour of cells at the most fundamental level by one single genetic modification is therefore potentially very powerful and wide ranging. This paper presents an overview of retinal gene therapy at the current time and highlights the future therapeutic potential for a number of diseases that are currently incurable.

  11. 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

  12. 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

  13. Pathology of articular cartilage and synovial membrane from elbow joints with and without degenerative joint disease in domestic cats.

    PubMed

    Freire, M; Meuten, D; Lascelles, D

    2014-09-01

    The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role.

  14. Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

    PubMed Central

    Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

    2015-01-01

    Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4−/−Rdh8−/− (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration. PMID:25617130

  15. 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.

  16. 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

  17. Controversies about interspinous process devices in the treatment of degenerative lumbar spine diseases: past, present, and future.

    PubMed

    Gazzeri, Roberto; Galarza, Marcelo; Alfieri, Alex

    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.

  18. 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.

  19. 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

  20. Current drug patenting for retinal diseases: beyond VEGF inhibitors.

    PubMed

    Mucke, Hermann A M; Mucke, Peter M

    2010-01-01

    An analysis of patent applications that address strategies for the pharmacological treatment of retinal diseases that are not directly related to VEGF inhibition, published under the PCT during the 18-month period from January 2008 to June 2009, is presented. The largest number of therapeutic patent applications focused on attempts to correct visual cycle dysfunctions, complement overactivation or beta-amyloid deposition in drusen to control age-related macular degeneration (AMD). Biomarker-based and genetic diagnostic modalities that assess AMD risk were also frequently claimed in the patent applications, and have become a significant factor in patenting for ocular disorders. The fields of both visual cycle therapy and AMD biomarkers were dominated by non-corporate patent assignees. Diabetic retinopathy has not received as much attention from inventors compared with AMD; retinopathy of prematurity remains a field in which little specific patenting occurs.

  1. 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

  2. A meta-analysis of artificial total disc replacement versus fusion for lumbar degenerative disc disease

    PubMed Central

    Yajun, Wu; Xiuxin, Han; Cui, Cui

    2010-01-01

    Lumbar fusion has been developed for several decades and became the standard surgical treatment for symptomatic lumbar degenerative disc disease (DDD). Artificial total disc replacement (TDR), as an alternative for spinal arthrodesis, is becoming more commonly employed treating lumbar DDD. It is still uncertain whether TDR is more effective and safer than lumbar fusion. To systematically compare the effectiveness and safety of TDR to that of the fusion for the treatment of lumbar DDD, we performed a meta-analysis. Cochrane review methods were used to analyze all relevant randomized controlled trials published up to July 2009. Five relevant randomized controlled trials involving 837 patients were identified. Patients in TDR group have sightly better functioning and less back or leg pain without clinical significance, and significantly higher satisfaction status in TDR group compared with lumbar fusion group at the 2-year follow-up. But these outcomes are highly influenced by the study with BAK cage interbody fusion, the function/pain and patient satisfaction status are no longer significantly different between two groups after excluding this study. At 5 years, these outcomes are not significantly different between comparing groups. The complication and reoperation rate of two groups are similar both at 2 and at 5 years. In conclusion, TDR does not show significant superiority for the treatment of lumbar DDD compared with fusion. The benefits of motion preservation and the long-term complications are still unable to be concluded. More high-quality RCTs with long-term follow-up are needed. PMID:20364392

  3. 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

  4. Risk of degenerative ankle joint disease in volleyball players: study of former elite athletes.

    PubMed

    Gross, P; Marti, B

    1999-01-01

    To estimate the influence of long-term, high-intensity volleyball playing on premature osteoarthritis (OA) of the ankle joint, we examined a group of 22 former elite volleyball-players age (34 +/- 6 yrs.) who had played for at least 3 years in the highest volleyball league in Switzerland, and 19 normal healthy untrained controls (35 +/- 6 yrs.). Volleyball-athletes had played during an average of 5.5 (+/- 2) h/wk for 8.5 (+/- 3) yrs. Twenty of the 22 players had suffered from at least one ankle sprain (average: 3.5), 10 had had ruptures of the lateral ligaments (8 of them operated). Four players had severe mechanical instability, 5 a talar varus tilt in the stress X-ray of more than 8 degrees. Subchondral sclerosis and osteophytes were more prevalent in volleyballers than in controls (p < 0.001), while the difference in joint space was not significant. No severe grades of OA could be observed in these former elite volleyball players. Yet, a radiologic score of degenerative ankle disease was elevated in 19/22 of them, but only in 2/19 controls (p<0.001). In multiple regression analysis among athletes, the anterior drawer sign and a feeling of instability were the only significant and independent predictors of an increased radiological index (p = 0.003 and p = 0.02, respectively) from an initial set of 9 variables covering career length and intensity as volleyball player, clinical signs of ankle instability and age. Even if in the present study, athletes had clearly more radiologic findings than controls--such as spur formation and subchondral sclerosis--long-term, high-intensity volleyball playing alone could not be confirmed as an independent risk factor for OA of the ankle joint however, a combination of chronic lateral ankle instability with intensive volleyball playing could marginally increase the risk of ankle OA. PMID:10090465

  5. Retinitis pigmentosa and retinal oedema.

    PubMed Central

    Spalton, D J; Bird, A C; Cleary, P E

    1978-01-01

    Twenty-five patients with retinitis pigmentosa and retinal leakage were investigated. Oedema was present in dominant and X-linked inherited disease and is likely to be present in recessive disease as well. We suggest that this might be a general response seen in many types of tapeto-retinal degeneration to actively degenerating photoreceptors or pigment epithelium. Images PMID:638111

  6. [The vitreous and vitreoretinal interface: natural history and associated retinal diseases].

    PubMed

    Giusti, C

    2002-01-01

    Such significant correlations have been found between vitreal changes and retinal breaks that retinal detachment is now considered as a vitreoretinal disease. Concerning this issue, not only the posterior vitreous detachment seems to play an important role in the occurrence of rhegmatogenous retinal detachment but also the vitreoretinal interactions themself seem to be important in the pathogenesis of cystoid and diabetic macular edema, proliferative diabetic retinopathy, age-related macular degeneration, macular pucker, idiopathic macular hole and macular disease associated with optic disk pit. It seemed therefore useful to the author an updated review on alterations of the vitreoretinal interface and associated ocular diseases.

  7. The role of stem cell therapies in degenerative lumbar spine disease: a review.

    PubMed

    Oehme, David; Goldschlager, Tony; Rosenfeld, Jeffrey V; Ghosh, Peter; Jenkin, Graham

    2015-07-01

    Degenerative conditions of the lumbar spine are extremely common. Ninety percent of people over the age of 60 years have degenerative change on imaging; however, only a small minority of people will require spine surgery (Hicks et al. Spine (Phila Pa 1976) 34(12):1301-1306, 2009). This minority, however, constitutes a core element of spinal surgery practice. Whilst the patient outcomes from spinal surgeries have improved in recent years, some patients will remain with pain and disability despite technically successful surgery. Advances in regenerative medicine and stem cell therapies, particularly the use of mesenchymal stem cells and allogeneic mesenchymal precursor cells, have led to numerous clinical trials utilising these cell-based therapies to treat degenerative spinal conditions. Through cartilage formation and disc regeneration, fusion enhancement or via modification of pain pathways, stem cells are well suited to enhance spinal surgery practice. This review will focus on the outcomes of lumbar spinal procedures and the role of stem cells in the treatment of degenerative lumbar conditions to enhance clinical practice. The current status of clinical trials utilising stem cell therapies will be discussed, providing clinicians with an overview of the various cell-based treatments likely to be available to patients in the near future.

  8. 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

  9. 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

  10. Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

    PubMed

    Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

    2014-01-01

    Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR.

  11. [The development of organization of medical care to patients with degenerative dystrophic diseases of lumbosacral section of spine].

    PubMed

    2012-01-01

    The article deals with issues of development of organizational technologies in the field of medical care of patients with degenerative dystrophic diseases of lumbosacral section of spine. The comprehensive evaluation of the process of medical care provision to this category of patients revealed the need in measures concerning the reconstruction and development of effectiveness of process. The model is elaborated concerning medical cary of patients with backache with the purpose to establish the succession between various stages of medical care provision. The issues of rational distribution of manpower resources and exclusion of duplication of activities on different stages of the process are considered.

  12. Retinal implants: a systematic review.

    PubMed

    Chuang, Alice T; Margo, Curtis E; Greenberg, Paul B

    2014-07-01

    Retinal implants present an innovative way of restoring sight in degenerative retinal diseases. Previous reviews of research progress were written by groups developing their own devices. This systematic review objectively compares selected models by examining publications describing five representative retinal prostheses: Argus II, Boston Retinal Implant Project, Epi-Ret 3, Intelligent Medical Implants (IMI) and Alpha-IMS (Retina Implant AG). Publications were analysed using three criteria for interim success: clinical availability, vision restoration potential and long-term biocompatibility. Clinical availability: Argus II is the only device with FDA approval. Argus II and Alpha-IMS have both received the European CE Marking. All others are in clinical trials, except the Boston Retinal Implant, which is in animal studies. Vision restoration: resolution theoretically correlates with electrode number. Among devices with external cameras, the Boston Retinal Implant leads with 100 electrodes, followed by Argus II with 60 electrodes and visual acuity of 20/1262. Instead of an external camera, Alpha-IMS uses a photodiode system dependent on natural eye movements and can deliver visual acuity up to 20/546. Long-term compatibility: IMI offers iterative learning; Epi-Ret 3 is a fully intraocular device; Alpha-IMS uses intraocular photosensitive elements. Merging the results of these three criteria, Alpha-IMS is the most likely to achieve long-term success decades later, beyond current clinical availability. PMID:24403565

  13. 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.

  14. 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.

  15. 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

  16. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis

    PubMed Central

    Feng, Yanming; Li, Jianli; Zhang, Wei; Wang, Jing; Lewis, Richard A.; Wong, Lee-Jun

    2016-01-01

    Purpose When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives. Methods We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy. Results Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42) of the unsolved cases. Conclusion Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases. PMID:27788217

  17. 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

  18. 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

  19. 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

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

    PubMed

    Barrey, Cédric; Jund, Jérôme; Noseda, Olivier; Roussouly, Pierre

    2007-09-01

    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 degrees and 51.6 degrees, respectively, versus 52 degrees 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

  1. 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

  2. [Retinal vascular changes--predictive and prognostic factor in systemic disease].

    PubMed

    Vicol, Anca Delia; Bogdănici, Tudor; Bogdănici, Camelia

    2014-01-01

    The retinal circulation represents a unique window for the direct, non invazive in vivo status of the systemic mycrocirculation, but it can also offer scientific support for theories related strictly to ocular diseases, such as glaucoma (vascular theory). The interaction between intraocular pressure, retinal vessels and cerebrospinal fluid pressure located at the retrolaminar part of the optic nerve has been of great interest for both ophthalmologists or neuroscientists, both clinicians and researchers. The retinal vascular bed has structural and functional similarities with other vascular teritories such as Central Nervous System (CNS), kidneys and heart, so as for the ophthalmologist any vascular change in the retina can signalize a systemic disease (diabetes mellitus, stroke, arterial hypertension) that is more or less symptomatic for the patient. The purpose of this meta-analysis was to reviview recent literature data related to the connections between different hemodynamic structures and their impact on the retinal blood flow.

  3. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 1: introduction and methodology.

    PubMed

    Kaiser, Michael G; Eck, Jason C; Groff, Michael W; Watters, William C; Dailey, Andrew T; Resnick, Daniel K; Choudhri, Tanvir F; Sharan, Alok; Wang, Jeffrey C; Mummaneni, Praveen V; Dhall, Sanjay S; Ghogawala, Zoher

    2014-07-01

    Fusion procedures are an accepted and successful management strategy to alleviate pain and/or neurological symptoms associated with degenerative disease of the lumbar spine. In 2005, the first version of the "Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine" was published in the Journal of Neurosurgery: Spine. In an effort to incorporate evidence obtained since the original publication of these guidelines, an expert panel of neurosurgical and orthopedic spine specialists was convened in 2009. Topics reviewed were essentially identical to the original publication. Selected manuscripts from the first iteration of these guidelines as well as relevant publications between 2005 through 2011 were reviewed. Several modifications to the methodology of guideline development were adopted for the current update. In contrast to the 2005 guidelines, a 5-tiered level of evidence strategy was employed, primarily allowing a distinction between lower levels of evidence. The qualitative descriptors (standards/guidelines/options) used in the 2005 recommendations were abandoned and replaced with grades to reflect the strength of medical evidence supporting the recommendation. Recommendations that conflicted with the original publication, if present, were highlighted at the beginning of each chapter. As with the original guideline publication, the intent of this update is to provide a foundation from which an appropriate treatment strategy can be formulated.

  4. Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease.

    PubMed

    Lee, Jee-Young; Kim, Jae Min; Ahn, Jeeyun; Kim, Han-Joon; Jeon, Beom S; Kim, Tae Wan

    2014-01-01

    Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.

  5. Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

    PubMed Central

    Mastropasqua, Rodolfo; Di Antonio, Luca; Di Staso, Silvio; Agnifili, Luca; Di Gregorio, Angela; Ciancaglini, Marco; Mastropasqua, Leonardo

    2015-01-01

    Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A. PMID:26491548

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Dietary hyperglycemia, glycemic index and metabolic retinal diseases.

    PubMed

    Chiu, Chung-Jung; Taylor, Allen

    2011-01-01

    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 (0-2h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4-6h). 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 as 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

  12. 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

  13. Analysis of the pre-retinal opacities in Gaucher Disease using spectral domain optical coherent tomography.

    PubMed

    Sheck, Leo H N; Wilson, Callum J; Vincent, Andrea L

    2012-12-01

    Fundal opacities have been reported in patients with Gaucher disease, a rare autosomal recessive lysosomal storage disease, prior to the advent of optical coherent tomography. This report provides a detailed analysis of the fundal opacities in a 14-year-old girl with genetically proven Gaucher disease using spectral domain optical coherent tomography. It illustrates clearly that these opacities were pre-retinal opacities located at the vitreo-retinal interface associated with localized posterior vitreous detachments, rather than vitreous opacities as previously suggested in the literature. PMID:22950450

  14. 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

  15. Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients.

    PubMed

    Staal, A; Meerwaldt, J D; van Dongen, K J; Mulder, P G; Busch, H F

    1990-03-01

    We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements. PMID:2358820

  16. Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients.

    PubMed

    Staal, A; Meerwaldt, J D; van Dongen, K J; Mulder, P G; Busch, H F

    1990-03-01

    We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Association of rs731236 polymorphism in the vitamin D receptor gene with degenerative disc disease: evidence from a meta-analysis

    PubMed Central

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

    2015-01-01

    The purpose of this study was to investigate the association between the rs731236 polymorphism in the vitamin D receptor gene and degenerative disc disease, especially in Chinese. We elaborately searched the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed and EMBASE databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. A total of 10 studies involving 1,220 cases and 1,225 controls were included in the present study. Overall, no evidence of significant risk between rs731236 polymorphism and degenerative disc disease was found in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by sample size in Chinese population show that sample size may be the primary source of heterogeneity. This meta-analysis suggested that the rs731236 polymorphism may not be associated with degenerative disc disease. However, for Asians, there existed some diversities, especially in Chinese population. Therefore, a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease. PMID:26309717

  3. The role of Toll-like receptors in retinal ischemic diseases

    PubMed Central

    Xu, Wen-Qin; Wang, Yu-Sheng

    2016-01-01

    Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia-reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells. Activation of TLRs in retina could initiate a complex signal transduction cascade, induce the production of inflammatory cytokines and regulate the level of co-stimulatory molecules, which play prominent roles in the pathogenesis of retinal ischemic diseases. In this review, we summarized current studies about the relationship between TLRs and ischemic retinopathy. A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions.

  4. The role of Toll-like receptors in retinal ischemic diseases.

    PubMed

    Xu, Wen-Qin; Wang, Yu-Sheng

    2016-01-01

    Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia-reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells. Activation of TLRs in retina could initiate a complex signal transduction cascade, induce the production of inflammatory cytokines and regulate the level of co-stimulatory molecules, which play prominent roles in the pathogenesis of retinal ischemic diseases. In this review, we summarized current studies about the relationship between TLRs and ischemic retinopathy. A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions. PMID:27672603

  5. The role of Toll-like receptors in retinal ischemic diseases

    PubMed Central

    Xu, Wen-Qin; Wang, Yu-Sheng

    2016-01-01

    Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia-reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells. Activation of TLRs in retina could initiate a complex signal transduction cascade, induce the production of inflammatory cytokines and regulate the level of co-stimulatory molecules, which play prominent roles in the pathogenesis of retinal ischemic diseases. In this review, we summarized current studies about the relationship between TLRs and ischemic retinopathy. A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions. PMID:27672603

  6. 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…

  7. 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 - ...

  8. Retinal microglia: just bystander or target for therapy?

    PubMed

    Karlstetter, Marcus; Scholz, Rebecca; Rutar, Matt; Wong, Wai T; Provis, Jan M; Langmann, Thomas

    2015-03-01

    Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.

  9. The Specificity of Colored Lenses as Visual Aids in Retinal Disease.

    ERIC Educational Resources Information Center

    Gawande, A.; And Others

    1992-01-01

    This study of the effects of lenses of different colors on the visual abilities and comfort of 20 patients with retinal disease found that, in home trials, the critical issue was density more than color. Office tests of visual acuity and contrast sensitivity with colored lenses did not predict subjective benefit. (Author/JDD)

  10. 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

  11. 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

  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.

  13. 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

  14. 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

  15. 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.

  16. Oleuropein Aglycone: A Possible Drug against Degenerative Conditions. In Vivo Evidence of its Effectiveness against Alzheimer's Disease.

    PubMed

    Casamenti, Fiorella; Grossi, Cristina; Rigacci, Stefania; Pantano, Daniela; Luccarini, Ilaria; Stefani, Massimo

    2015-01-01

    The amyloid plaques and neurofibrillary tangles found in the Alzheimer's disease (AD) brain arise as a result of self-assembly into fibrillar material of amyloid-β protein (Aβ) and hyperphosphorylated tau, respectively, through a pathological process starting with the appearance of aggregation nuclei and neurotoxic oligomers. Accordingly, the search of inhibitors of oligomer nucleation and growth is considered a promising target to prevent amyloid toxicity. In recent years, a number of dietary factors including antioxidants, vitamins, and polyphenols have been characterized for their ability to protect cells stressed by several factors including the presence of amyloid deposits as well as to inhibit amyloid self-assembly and cytotoxicity and some of them are currently in clinical trial. The present review summarizes the findings on the beneficial effects against neurodegeneration and other peripheral inflammatory and degenerative diseases of oleuropein aglycone (OLE), a natural phenol abundant in the extra virgin olive oil. The data presently available suggest that OLE could provide a protective and therapeutic effect against a number of pathologies, including AD as well as obesity, type 2 diabetes, non-alcoholic hepatitis, and other natural or experimentally-induced pathological conditions. Such a protection could result, at least in part, in a remarkable improvement of the pathological signs arising from stress conditions including oxidative stress, an excessive inflammatory response, and the presence of cytotoxic aggregated material. In particular, the recent data on the cellular and molecular correlates of OLE neuroprotection suggest it could also play a therapeutic role against AD.

  17. 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).

  18. 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

  19. Multi-resolution entropy analysis of gait symmetry in neurological degenerative diseases and amyotrophic lateral sclerosis.

    PubMed

    Liao, Fuyuan; Wang, Jue; He, Ping

    2008-04-01

    Gait rhythm of patients with Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) has been studied focusing on the fractal and correlation properties of stride time fluctuations. In this study, we investigated gait asymmetry in these diseases using the multi-resolution entropy analysis of stance time fluctuations. Since stance time is likely to exhibit fluctuations across multiple spatial and temporal scales, the data series were decomposed into appropriate levels by applying stationary wavelet transform. The similarity between two corresponding wavelet coefficient series in terms of their regularities at each level was quantified based on a modified sample entropy method and a weighted sum was then used as gait symmetry index. We found that gait symmetry in subjects with PD and HD, especially with ALS is significantly disturbed. This method may be useful in characterizing certain pathologies of motor control and, possibly, in monitoring disease progression and evaluating the effect of an individual treatment.

  20. Multi-resolution entropy analysis of gait symmetry in neurological degenerative diseases and amyotrophic lateral sclerosis.

    PubMed

    Liao, Fuyuan; Wang, Jue; He, Ping

    2008-04-01

    Gait rhythm of patients with Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) has been studied focusing on the fractal and correlation properties of stride time fluctuations. In this study, we investigated gait asymmetry in these diseases using the multi-resolution entropy analysis of stance time fluctuations. Since stance time is likely to exhibit fluctuations across multiple spatial and temporal scales, the data series were decomposed into appropriate levels by applying stationary wavelet transform. The similarity between two corresponding wavelet coefficient series in terms of their regularities at each level was quantified based on a modified sample entropy method and a weighted sum was then used as gait symmetry index. We found that gait symmetry in subjects with PD and HD, especially with ALS is significantly disturbed. This method may be useful in characterizing certain pathologies of motor control and, possibly, in monitoring disease progression and evaluating the effect of an individual treatment. PMID:17569571

  1. The Retinal Pigment Epithelium in Health and Disease

    PubMed Central

    Sparrrow, J.R.; Hicks, D.; Hamel, C.P.

    2014-01-01

    Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal cells that are strategically situated behind the photoreceptor (PR) cells. The inconspicuousness of this monolayer contrasts sharply with its importance [1]. The relationship between the RPE and PR cells is crucial to sight; this is evident from basic and clinical studies demonstrating that primary dysfunctioning of the RPE can result in visual cell death and blindness. RPE cells carry out many functions including the conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition. The magnitude of the demands imposed on this single layer of cells in order to execute these tasks, will become apparent to the reader of this review as will the number of clinical disorders that take origin from these cells. PMID:21091424

  2. Rod-cone interactions and analysis of retinal disease.

    PubMed Central

    Arden, G B; Hogg, C R

    1985-01-01

    Cone flicker threshold rises as the rods dark adapt, though the cone threshold to continuous light remains constant. The rise is normally about 1 log unit, but in certain patients who complain of night blindness it may be as great as 2.5 log units. In these persons the kinetics of the rod-cone interaction are those of the recovery of rod sensitivity. The rods impose a low-pass filter on the cones. This effect is absent in congenital nyctalopia and X-linked retinoschisis. We suggest that cone flicker is maintained through a feedback system involving horizontal cells, and when the rod dark current returns in dark adaptation this feedback is altered. Rod cone interaction thus tests rod dark current, and cases of abnormal interaction in patients with retinitis pigmentosa occur, which indicate that the transduction mechanism and the membrane dark current may be differentially affected. Images PMID:3873959

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

    PubMed

    Nopoulos, Peggy C

    2016-03-01

    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.

  4. An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases.

    PubMed

    Lorente-Cebrián, Silvia; Costa, André G V; Navas-Carretero, Santiago; Zabala, María; Laiglesia, Laura M; Martínez, J Alfredo; Moreno-Aliaga, María J

    2015-06-01

    Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome.

  5. An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases.

    PubMed

    Lorente-Cebrián, Silvia; Costa, André G V; Navas-Carretero, Santiago; Zabala, María; Laiglesia, Laura M; Martínez, J Alfredo; Moreno-Aliaga, María J

    2015-06-01

    Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome. PMID:25752887

  6. Potential new strategies for the treatment of ovarian infertility and degenerative diseases with autologous ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Copas, Pleas; Virant-Klun, Irma

    2006-04-01

    The 50-year-old and currently prevailing view that all oocytes in adult human ovaries persist from the fetal period of life is controversial as it clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal in adult human ovaries, and of the role of hormonal signals and third-party cells (tissue macrophages and T cells), could all be helpful in providing better understanding of the causes of ovarian infertility, its prevention and potential therapy. In addition, the authors recently reported differentiation of distinct cell types and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. It is possible that fertilisation of such eggs will open up new opportunities for providing genetically related children to infertile women for whom conventional in vitro fertilisation has failed. As ovarian stem cells appear to represent a new type of totipotent adult stem cell, they could also be utilised for autologous stem cell therapy of degenerative diseases, without any involvement of allogeneic embryonic stem cells and somatic cell nuclear transfer.

  7. Application of stable isotopic techniques in the prevention of degenerative diseases like obesity and NIDDM in developing societies.

    PubMed

    Shetty, Prakash; Iyengar, Venkatesh; Sawaya, Ana; Diaz, Erik; Ma, Guansheng; Hernandez-Triana, Manuel; Yajnik, Chittaranjan; Forrester, Terrence; Valencia, Mauro; Rush, Elaine; Adeyemo, Adebowale; Jahoor, Farook; Roberts, Susan

    2002-09-01

    Economic development in developing societies characterized by industrialization, urbanization, and globalization has seen the emergence of an epidemic of diet- and life-style-related chronic degenerative diseases. A research project was initiated under the aegis of the International Atomic Energy Agency (IAEA), Vienna, Austria under its Coordinated Research Programme (CRP) to promote the use of stable isotopic techniques to document the extent of the problem and to understand the determinants of this epidemic. The principal objectives of this CRP involving countries both in the North and the South are to define the magnitude of the problem of obesity and non-insulin dependent diabetes mellitus (NIDDM) in developing countries, to identify the vulnerable groups at increased risk, and to attempt to describe the metabolic and physiological mechanisms underlying this phenomenon. These comparative international studies of obesity and NIDDM are looking at the effects of childhood malnutrition (Brazil) and socioeconomic differentials (Mexico) on adult risk factors; the composition of the daily diet on obesity (Chile); levels of patterns of physical activity of older adults (China) as well as their influence on weight gain and obesity (Cuba, Nigeria); the impact of body composition and energy expenditure on the evolution frank diabetes from impaired glucose tolerance (Jamaica), and of body compositional changes and the role of inflammatory cytokines on impaired glucose tolerance (India). The last study conducted in New Zealand was aimed at comparing the energy expenditures of Maori (Pacific Island) with New Zealanders of European descent.

  8. Instrumented posterior lumbar interbody fusion (PLIF) with interbody fusion device (Cage) in degenerative disc disease (DDD): 3 years outcome.

    PubMed

    Ahsan, M K; Hossain, M A; Sakeb, N; Khan, S I; Zaman, N

    2013-10-01

    This prospective interventional study carried out at Bangabandhu Sheikh Mujib Medical University and a private hospital in Dhaka, Bangladesh during the period from October 2003 to September 2011. Surgical treatment of degenerative disc disease (DDD) should aim to re-expand the interbody space and stabilize until fusion is complete. The present study conducted to find out the efficacy of using interbody fusion device (Cage) to achieve interbody space re-expansion and fusion in surgical management of DDD. We have performed the interventional study on 53 patients, 42 female and 11 male, with age between 40 to 67 years. All the patients were followed up for 36 to 60 months (average 48 months). Forty seven patients were with spondylolisthesis and 06 with desiccated disc. All subjects were evaluated with regard to immediate and long term complications, radiological fusion and interbody space re-expansion and maintenance. The clinical outcome (pain and disability) was scored by standard pre and postoperative questionnaires. Intrusion, extrusion and migration of the interbody fusion cage were also assessed. Forty seven patients were considered to have satisfactory outcome in at least 36 months follow up. Pseudoarthrosis developed in 04 cases and 06 patients developed complications. In this series posterior lumbar interbody fusion (PLIF) with interbody cage and instrumentation in DDD showed significant fusion rate and maintenance of interbody space. Satisfactory outcome observed in 88.68% cases.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases.

    PubMed

    Williams, A C; Ramsden, D B

    2005-01-01

    Monkeys and man are very closely related genetically. Yet intellectually there are big differences and they suffer from a broad range of different diseases. For example, monkeys do not get Parkinson's or Alzheimer's disease. The former is surprising given that both get parkinsonism from MPTP poisoning and the latter initially less surprising as the cortex predominantly affected in Alzheimer's never developed as fully in the monkey. Man is an omnivore whilst other primates are predominantly herbivores. The one primate who was almost wholly carnivorous was Neanderthal man who became extinct. Red meat has a high content of Nicotinamide, Choline, and methyl donors. The enzyme NNMT converts nicotinamide to N-methyl-nicotinamide using SAM as the methyl donor. It is not present to any degree in herbivores. It has recently been shown to be present in human brain and up regulated in Parkinson's disease. Omnivores presumably need it for nicotinamide homeostasis but the production of N-methyl-nicotinamide will also be beneficial as it will reduce the export of Choline from neurones. Both will aid brain growth and development. However, as N-methyl-nicotinamide resembles MPTP it could cause parkinsonism later in life for man but not monkeys as they would be predicted not to have as much NNMT. Humans with a diet low in Nicotinamide,Choline or methyl donors early in life and low enzyme activity may be prone to Alzheimer's as their brain and therefore its reserves may never have developed as fully. The possession of NNMT plus a diet rich in Nicotinamide, Choline and methyl providers may explain many of the advantages but also the disadvantages of the human condition. One prediction is that a diet rich in these micronutrients whilst young will improve brain development and reduce the risk of Alzheimer's but that a lower dose later in life will reduce the risk of Parkinsonism. A second prediction is that it will become clear that dietary factors including vitamins are signalers and

  14. Ipsilateral atrophy of paraspinal and psoas muscle in unilateral back pain patients with monosegmental degenerative disc disease

    PubMed Central

    Ploumis, A; Michailidis, N; Christodoulou, P; Kalaitzoglou, I; Gouvas, G; Beris, A

    2011-01-01

    Objectives The aim of this study was to assess the cross-sectional area (CSA) of both paraspinal and psoas muscles in patients with unilateral back pain using MRI and to correlate it with outcome measures. Methods 40 patients, all with informed consent, with a minimum of 3 months of unilateral back pain with or without sciatica and one-level disc disease on MRI of the lumbosacral spine were included. Patients were evaluated with self-report measures regarding pain (visual analogue score) and disability (Oswestry disability index). The CSA of multifidus, erector spinae, quadratus lumborum and psoas was measured at the disc level of pathology and the two adjacent disc levels, bilaterally. Comparison of CSAs of muscles between the affected vs symptomless side was carried out with Student's t-test and correlations were conducted with Spearman's test. Results The maximum relative muscle atrophy (% decrease in CSA on symptomatic side) independent of the level was 13.1% for multifidus, 21.8% for erector spinae, 24.8% for quadratus lumborum and 17.1% for psoas. There was significant difference (p<0.05) between sides (symptomatic and asymptomatic) in CSA of multifidus, erector spinae, quadratus lumborum and psoas. However, no statistically significant correlation was found between the duration of symptoms (average 15.5 months), patient's pain (average VAS 5.3) or disability (average ODI 25.2) and the relative muscle atrophy. Conclusion In patients with long-standing unilateral back pain due to monosegmental degenerative disc disease, selective multifidus, erector spinae, quadratus lumborum and psoas atrophy develops on the symptomatic side. Radiologists and clinicians should evaluate spinal muscle atrophy of patients with persistent unilateral back pain. PMID:21081573

  15. A Multiplex High-Throughput Gene Expression Assay to Simultaneously Detect Disease and Functional Markers in Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium

    PubMed Central

    Ferrer, Marc; Corneo, Barbara; Davis, Janine; Wan, Qin; Miyagishima, Kiyoharu Joshua; King, Rebecca; Maminishkis, Arvydas; Marugan, Juan; Sharma, Ruchi; Shure, Michael; Temple, Sally; Miller, Sheldon

    2014-01-01

    There is continuing interest in the development of lineage-specific cells from induced pluripotent stem (iPS) cells for use in cell therapies and drug discovery. Although in most cases differentiated cells show features of the desired lineage, they retain fetal gene expression and do not fully mature into “adult-like” cells. Such cells may not serve as an effective therapy because, once implanted, immature cells pose the risk of uncontrolled growth. Therefore, there is a need to optimize lineage-specific stem cell differentiation protocols to produce cells that no longer express fetal genes and have attained “adult-like” phenotypes. Toward that goal, it is critical to develop assays that simultaneously measure cell function and disease markers in high-throughput format. Here, we use a multiplex high-throughput gene expression assay that simultaneously detects endogenous expression of multiple developmental, functional, and disease markers in iPS cell-derived retinal pigment epithelium (RPE). We optimized protocols to differentiate iPS cell-derived RPE that was then grown in 96- and 384-well plates. As a proof of principle, we demonstrate differential expression of eight genes in iPS cells, iPS cell-derived RPE at two different differentiation stages, and primary human RPE using this multiplex assay. The data obtained from the multiplex gene expression assay are significantly correlated with standard quantitative reverse transcription-polymerase chain reaction-based measurements, confirming the ability of this high-throughput assay to measure relevant gene expression changes. This assay provides the basis to screen for compounds that improve RPE function and maturation and target disease pathways, thus providing the basis for effective treatments of several retinal degenerative diseases. PMID:24873859

  16. Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects.

    PubMed

    Beach, Thomas G; Carew, Jeremiah; Serrano, Geidy; Adler, Charles H; Shill, Holly A; Sue, Lucia I; Sabbagh, Marwan N; Akiyama, Haruhiko; Cuenca, Nicolás

    2014-06-13

    Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N=9), dementia with Lewy bodies (DLB; N=3), Alzheimer's disease (N=3), progressive supranuclear palsy (N=2) as well as elderly normal control subjects (N=4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

  17. 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

  18. The yeast prions [PSI+] and [URE3] are molecular degenerative diseases.

    PubMed

    Wickner, Reed B; Edskes, Herman K; Bateman, David; Kelly, Amy C; Gorkovskiy, Anton

    2011-01-01

    The yeast prions [URE3] and [PSI] are not found in wild strains, suggesting they are not an advantage. Prion-forming ability is not conserved, even within Saccharomyces, suggesting it is a disease. Prion domains have non-prion functions, explaining some conservation of sequence. However, in spite of the sequence being constrained in evolution by these non-prion functions, the prion domains vary more rapidly than the remainder of the molecule, and these changes produce a transmission barrier, suggesting that these changes were selected to block prion infection. Yeast prions [PSI] and [URE3] induce a cellular stress response (Hsp104 and Hsp70 induction), suggesting the cells are not happy about being infected. Recently, we showed that the array of [PSI] and [URE3] prions includes a majority of lethal or very toxic variants, a result not expected if either prion were an adaptive cellular response to stress.

  19. Interspinous spacer decompression (X-STOP) for lumbar spinal stenosis and degenerative disk disease: a multicenter study with a minimum 3-year follow-up.

    PubMed

    Puzzilli, Fabrizio; Gazzeri, Roberto; Galarza, Marcelo; Neroni, Massimiliano; Panagiotopoulos, Konstantinos; Bolognini, Andrea; Callovini, Giorgio; Agrillo, Umberto; Alfieri, Alex

    2014-09-01

    Interspinous distraction devices provide an effective treatment for patients suffering from lumbar spinal stenosis and/or degenerative disk disease. The aim of this multicenter study was the prospective evaluation of patients treated for symptomatic lumbar spinal stenosis with interspinous process decompression (IPD) implants compared with a population of patients managed with conservative treatment. 542 patients affected by symptomatic lumbar spine degenerative disease were enrolled in a controlled trial. 422 patients underwent surgical treatment consisting of X-STOP device implantation, whereas 120 control cases were managed conservatively. Both patient groups underwent follow-up evaluations at 6, 12, 24, and 36 months using the Zurich Claudication Questionnaire, the Visual Analog Scale score and spinal lumbar X-rays, CT scans and MR imaging. One-year follow-up evaluation revealed positive good results in the 83.5% of patients treated with IPD with respect to 50% of the nonoperative group cases. During the first three years, in 38 out of the 120 control cases, a posterior decompression and/or spinal fixation was performed because of unsatisfactory results of the conservative therapy. In 24 of 422 patients, the IPD device had to be removed, and a decompression and/or pedicle screw fixation was performed because of the worsening of neurological symptoms. Our results support the effectiveness of surgery in patients with stenosis. IPD may offer an effective and less invasive alternative to classical microsurgical posterior decompression in selected patients with spinal stenosis and lumbar degenerative disk diseases.

  20. Novel endogenous glycan therapy for retinal diseases: safety, in vitro stability, ocular pharmacokinetic modeling, and biodistribution.

    PubMed

    Swaminathan, Shankar; Li, Huiling; Palamoor, Mallika; de Obarrio, Walter T Luchsinger; Madhura, Dorababu; Meibohm, Bernd; Jablonski, Monica M

    2014-03-01

    Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [(3)H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous > retina > sclera/choroid > aqueous humor > cornea > lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [(3)H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

  1. 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

  2. Therapeutic Opportunities for Caffeine and A2A Receptor Antagonists in Retinal Diseases.

    PubMed

    Boia, Raquel; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-01-01

    Caffeine, the major component of coffee, is the most consumed psychostimulant in the world. Caffeine is an adenosine analog and acts as a nonselective adenosine receptor antagonist. The majority of the effects of caffeine are mainly mediated by the blockade of adenosine receptors, and the proved neuroprotective effects of caffeine in brain disorders have been mimicked by the blockade of adenosine A2A receptor (A2AR). A growing body of evidence demonstrates that microglia-mediated neuroinflammation plays a key role in the pathophysiology of brain and retinal diseases. Moreover, the control of microglia reactivity by blocking A2AR has been proposed to be the mechanism underlying the observed protective effects of caffeine. Hence, it is conceivable that caffeine and A2AR antagonists offer therapeutic value for the treatment of retinal diseases, mainly those involving microglia-mediated neuroinflammation.

  3. Therapeutic Opportunities for Caffeine and A2A Receptor Antagonists in Retinal Diseases.

    PubMed

    Boia, Raquel; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-01-01

    Caffeine, the major component of coffee, is the most consumed psychostimulant in the world. Caffeine is an adenosine analog and acts as a nonselective adenosine receptor antagonist. The majority of the effects of caffeine are mainly mediated by the blockade of adenosine receptors, and the proved neuroprotective effects of caffeine in brain disorders have been mimicked by the blockade of adenosine A2A receptor (A2AR). A growing body of evidence demonstrates that microglia-mediated neuroinflammation plays a key role in the pathophysiology of brain and retinal diseases. Moreover, the control of microglia reactivity by blocking A2AR has been proposed to be the mechanism underlying the observed protective effects of caffeine. Hence, it is conceivable that caffeine and A2AR antagonists offer therapeutic value for the treatment of retinal diseases, mainly those involving microglia-mediated neuroinflammation. PMID:26959995

  4. 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

  5. Chronic kidney disease and the severity of coronary artery disease and retinal microvasculature changes: a cross-sectional study

    PubMed Central

    Au, Cheryl; Mitchell, Paul; Liew, Gerald; Plant, Adam J. H.; Wang, Sarah B.; Chiha, Joseph; Thiagalingam, Aravinda; Burlutsky, George; Gopinath, Bamini

    2016-01-01

    Background Prior studies have suggested the association between incidence of coronary artery disease (CAD) with chronic kidney disease (CKD) and poor glomerular filtration function. However to the best of our knowledge, few studies have specifically assessed this relationship based on the severity of CAD as quantified using Extent and Gensini scores. Methods Between June 2009 and January 2012, data were collected from 1,680 participants as part of the Australian Heart Eye Study (AHES) cohort. Coronary angiograms were scored according to Gensini (severity) and Extent scores. Retinal vessel calibres were measured using validated semi-automated software. Potential confounders were adjusted for using multivariate analysis. Results There were no significant associations found between CKD status with Extent and Gensini scores for CAD severity, both unadjusted and when adjusted for confounding factors. In unadjusted analyses, a significant association between CKD and narrower retinal arteriolar diameter was observed (P=0.0072). After multivariate adjustment, the association between CKD and retinal arteriolar diameter was attenuated and was no longer significant (P=0.1466). No associations were observed between retinal venular calibre and prevalent CKD. Conclusions The present study demonstrated no independent associations between CKD and CAD severity. These results warrant validation by future large, prospective longitudinal studies. PMID:27621866

  6. 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

  7. Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain.

    PubMed

    Heckman, Karin L; DeCoteau, William; Estevez, Ana; Reed, Kenneth J; Costanzo, Wendi; Sanford, David; Leiter, James C; Clauss, Jennifer; Knapp, Kylie; Gomez, Carlos; Mullen, Patrick; Rathbun, Elle; Prime, Kelly; Marini, Jessica; Patchefsky, Jamie; Patchefsky, Arthur S; Hailstone, Richard K; Erlichman, Joseph S

    2013-12-23

    Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease. The CeNPs are 2.9 nm in diameter, monodispersed and have a -23.5 mV zeta potential when stabilized with citrate/EDTA. This stabilizer coating resists being 'washed' off in physiological salt solutions, and the CeNPs remain monodispersed for long durations in high ionic strength saline. The plasma half-life of the CeNPs is ∼4.0 h, far longer than previously described, stabilized ceria nanoparticles. When administered intravenously to mice, the CeNPs were well tolerated and taken up by the liver and spleen much less than previous nanoceria formulations. The CeNPs were also able to penetrate the brain, reduce reactive oxygen species levels, and alleviate clinical symptoms and motor deficits in mice with a murine model of multiple sclerosis. Thus, CeNPs may be useful in mitigating tissue damage arising from free radical accumulation in biological systems.

  8. Lumbar Interbody Fusion Outcomes in Degenerative Lumbar Disease : Comparison of Results between Patients Over and Under 65 Years of Age

    PubMed Central

    Jo, Dae-Jean; Jun, Jae-Kyun; Kim, Ki-Tack

    2010-01-01

    Objective To evaluate the clinical and radiological outcomes of lumbar interbody fusion and its correlation with various factors (e.g., age, comorbidities, fusion level, bone quality) in patients over and under 65 years of age who underwent lumbar fusion surgery for degenerative lumbar disease. Methods One-hundred-thirty-three patients with lumbar degenerative disease underwent lumbar fusion surgery between June 2006 and June 2007 and were followed for more than one year. Forty-eight (36.1%) were older than 65 years of age (group A) and 85 (63.9%) were under 65 years of age (group B). Diagnosis, comorbidities, length of hospital stay, and perioperative complications were recorded. The analysis of clinical outcomes was based on the visual analogue scale (VAS). Radiological results were evaluated using plain radiographs. Clinical outcomes, radiological outcomes, length of hospital stay, and complication rates were analyzed in relation to lumbar fusion level, the number of comorbidities, bone mineral density (BMD), and age. Results The mean age of the patients was 61.2 years (range, 33-86 years) and the mean BMD was -2.2 (range, -4.8 to -2.8). The mean length of hospital stay was 15.0 days (range, 5-60 days) and the mean follow-up was 23.0 months (range, 18-30 months). Eighty-five (64.0%) patients had more than one preoperative comorbidities. Perioperative complications occurred in 27 of 133 patients (20.3%). The incidence of overall complication was 22.9% in group A, and 18.8% in group B but there was no statistical difference between the two groups. The mean VAS scores for the back and leg were significantly decreased in both groups (p < 0.05), and bony fusion was achieved in 125 of 133 patients (94.0%). There was no significant difference in bony union rates between groups A and B (91.7% in group A vs. 95.3% in group B, p = 0.398). In group A, perioperative complications were more common with the increase in fusion level (p = 0.027). Perioperative complications in

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Current and future perspectives on lumbar degenerative disc disease: a UK survey exploring specialist multidisciplinary clinical opinion

    PubMed Central

    McGregor, Alison H

    2016-01-01

    Objectives Despite lumbar degenerative disc disease (LDDD) being significantly associated with non-specific low back pain and effective treatment remaining elusive, specialist multidisciplinary clinical stakeholder opinion remains unexplored. The present study examines the views of such experts. Design A reliable and valid electronic survey was designed to establish trends using theoretical constructs relating to current assessment and management practices. Clinicians from the Society of Back Pain Research (SBPR) UK were invited to take part. Quantitative data were collated and coded using Bristol Online Surveys (BOS) software, and content analysis was used to systematically code and categorise qualitative data. Setting Specialist multidisciplinary spinal interest group in the UK. Participants 38/141 clinically active, multidisciplinary SBPR members with specialist spinal interest participated. Among them, 84% had >9 years postgraduate clinical experience. Interventions None. Outcome measures Frequency distributions were used to establish general trends in quantitative data. Qualitative responses were coded and categorised in relation to each theme and percentage responses were calculated. Results LDDD symptom recurrence, in the absence of psychosocial influence, was associated with physical signs of joint stiffness (26%), weakness (17%) and joint hypermobility (6%), while physical factors (21%) and the ability to adapt (11%) were postulated as reasons why some experience pain and others do not. No one management strategy was supported exclusively or with consensus. Regarding effective modalities, there was no significant difference between allied health professional and medic responses (p=0.1–0.8). The future of LDDD care was expressed in terms of improvements in patient communication (35%), patient education (38%) and treatment stratification (24%). Conclusions Results suggest that multidisciplinary expert spinal clinicians appear to follow UK

  15. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials.

    PubMed

    Oehme, David; Goldschlager, Tony; Ghosh, Peter; Rosenfeld, Jeffrey V; Jenkin, Graham

    2015-01-01

    Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed. PMID:26074979

  16. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    PubMed Central

    Oehme, David; Goldschlager, Tony; Ghosh, Peter; Rosenfeld, Jeffrey V.; Jenkin, Graham

    2015-01-01

    Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed. PMID:26074979

  17. Translating Induced Pluripotent Stem Cells from Bench to Bedside: Application to Retinal Diseases

    PubMed Central

    Cramer, Alona O.; MacLaren, Robert E.

    2013-01-01

    Induced pluripotent stem cells (iPSc) are a scientific and medical frontier. Application of reprogrammed somatic cells for clinical trials is in its dawn period; advances in research with animal and human iPSc are paving the way for retinal therapies with the ongoing development of safe animal cell transplantation studies and characterization of patient-specific and disease-specific human iPSc. The retina is an optimal model for investigation of neural regeneration; amongst other advantageous attributes, it is the most accessible part of the CNS for surgery and outcome monitoring. A recent clinical trial showing a degree of visual restoration via a subretinal electronic prosthesis implies that even a severely degenerate retina may have the capacity for repair after cell replacement through potential plasticity of the visual system. Successful differentiation of neural retina from iPSc and the recent generation of an optic cup from human ESc in-vitro increase the feasibility of generating an expandable and clinically suitable source of cells for human clinical trials. In this review we shall present recent studies that have propelled the field forward and discuss challenges in utilizing iPS cell derived retinal cells as reliable models for clinical therapies and as a source for clinical cell transplantation treatment for patients suffering from genetic retinal disease. PMID:23320477

  18. [Adult Refsum disease. A retinal dystrophy with therapeutic options].

    PubMed

    Rüther, K

    2005-08-01

    Adult Refsum disease is one of the few forms of tapetoretinal degenerations accessible for therapy. The disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety tissues. Beside tapetoretinal degeneration, additional symptoms are chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, skeletal malformations, and cardiac abnormalities. A diet low in phytanic acid leads to an amelioration of polyneuropathy and ataxia and slows or even stops the other manifestations. This beneficial effect of dietary precautions requires the need to get hold of as much patients as possible but better all of them. The ophthalmologist plays a crucial role to this end because of the early manifestation of the tapetoretinal degeneration. A delay of 11 years between the appearance of first symptoms and the diagnosis of Refsum disease, as reported in the literature, is not acceptable.

  19. 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.

  20. What can we learn about age-related macular degeneration from other retinal diseases?

    PubMed

    Zack, D J; Dean, M; Molday, R S; Nathans, J; Redmond, T M; Stone, E M; Swaroop, A; Valle, D; Weber, B H

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  1. Receptor-associated prorenin system in the pathogenesis of retinal diseases.

    PubMed

    Satofuka, Shingo; Kanda, Atsuhiro; Ishida, Susumu

    2012-06-01

    Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanisms whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling through the receptor. Although we found significant involvement of angiotensin II type 1 receptor (AT1-R) in intraocular inflammation and neovascularization, central pathologies of age-related macular degeneration and diabetic retinopathy, the association of RAPS with these vision-threatening disorders has not been defined. (P)RR blockade to murine disease models led to significant suppression of laser-induced choroidal neovascularization and diabetes-induced retinal inflammation together with the upregulation of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor (VEGF). Either the genetic ablation or the pharmacological blockade of AT1-R exhibited significant reduction of choroidal and retinal abnormalities, both of which were further suppressed by (P)RR blockade. (P)RR blockade inhibited ERK activation and the production of VEGF and MCP-1, but not ICAM-1, in AT1-R-deficient mice with retinal and choroidal disorders. These recent findings indicate significant contribution of RAPS to the pathogenesis of age-related macular degeneration and diabetic retinopathy.

  2. 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

  3. 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.

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

    PubMed Central

    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

    2016-01-01

    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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies.

    PubMed

    Herrero-Vanrell, Rocío; Bravo-Osuna, Irene; Andrés-Guerrero, Vanessa; Vicario-de-la-Torre, Marta; Molina-Martínez, Irene Teresa

    2014-09-01

    Pathologies affecting the posterior segment of the eye are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Successful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance maintained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future.

  11. Effect of posterior subsidence on cervical alignment after anterior cervical corpectomy and reconstruction using titanium mesh cages in degenerative cervical disease.

    PubMed

    Jang, Jae-Won; Lee, Jung-Kil; Lee, Jung-Heon; Hur, Hyuk; Kim, Tae-Wan; Kim, Soo-Han

    2014-10-01

    Subsidence after anterior cervical reconstruction using a titanium mesh cage (TMC) has been a matter of debate. The authors investigated and analyzed subsidence and its effect on clinical and radiologic parameters after cervical reconstruction using a TMC for degenerative cervical disease. Thirty consecutive patients with degenerative cervical spine disorders underwent anterior cervical corpectomy followed by reconstruction with TMC. Twenty-four patients underwent a single-level corpectomy, and six patients underwent a two-level corpectomy. Clinical outcomes were assessed using a Visual Analogue Scale (VAS), the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). Fusion status, anterior and posterior subsidence of the TMC, segmental angle (SA) and cervical sagittal angle (CSA) were assessed by lateral and flexion-extension radiographs of the neck. The mean follow-up period was 27.6 months (range, 24 to 49 months). The VAS, NDI and JOA scores were all significantly improved at the last follow-up. No instances of radiolucency or motion-related pseudoarthrosis were detected on radiographic analysis, yielding a fusion rate of 100%. Subsidence occurred in 28 of 30 patients (93.3%). The average anterior subsidence of the cage was 1.4 ± 0.9 mm, and the average posterior subsidence was 2.9 ± 1.2 mm. The SA and CSA at the final follow-up were significantly increased toward a lordotic angle. Anterior cervical reconstruction using TMC and plating in patients with cervical degenerative disease provides good clinical and radiologic outcomes. Cage subsidence occurred frequently, especially at the posterior part of the cage. Despite the prominent posterior subsidence of the TMC, SA and CSA were improved on final follow-up radiographs, suggesting that posterior subsidence may contribute to cervical lordosis.

  12. 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

  13. 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

  14. 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

  15. 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

    2016-08-29

    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.

  16. 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.

  17. 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

  18. 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 ...

  19. Photovoltaic retinal prosthesis with high pixel density

    NASA Astrophysics Data System (ADS)

    Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I.; Galambos, Ludwig; Smith, Richard; Harris, James S.; Sher, Alexander; Palanker, Daniel

    2012-06-01

    Retinal degenerative diseases lead to blindness due to loss of the `image capturing' photoreceptors, while neurons in the `image-processing' inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating the surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems that deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation is produced in normal and degenerate rat retinas, with pulse durations of 0.5-4 ms, and threshold peak irradiances of 0.2-10 mW mm-2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 µm bipolar pixel, demonstrating the possibility of a fully integrated photovoltaic retinal prosthesis with high pixel density.

  20. Photovoltaic Retinal Prosthesis with High Pixel Density.

    PubMed

    Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I; Galambos, Ludwig; Smith, Richard; Harris, James S; Sher, Alexander; Palanker, Daniel

    2012-06-01

    Retinal degenerative diseases lead to blindness due to loss of the "image capturing" photoreceptors, while neurons in the "image processing" inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm(2), two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density.

  1. Photovoltaic Retinal Prosthesis with High Pixel Density

    PubMed Central

    Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I.; Galambos, Ludwig; Smith, Richard; Harris, James S.; Sher, Alexander; Palanker, Daniel

    2012-01-01

    Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image processing” inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density. PMID:23049619

  2. [The use of minimally invasive instrumental spinal surgical technique in lumbar diseases of degenerative or traumatic origin].

    PubMed

    Schwarcz, Attila; Kasó, Gábor; Büki, András; Dóczi, Tamás

    2013-03-30

    Paradigm change has recently taken place in spine surgery with the application of minimally invasive techniques. Minimally invasive techniques have several advantages over the open traditional techniques: less blood loss, preservation of spine muscle integrity, shorter hospitalization, early mobilization, reduced pain levels, lower risk of infection. The presented cases cover following lumbar pathologies: segmental spinal instability, LV-SI grade II. spondylolisthesis, degenerative spondylolisthesis, spine trauma. Unilateral or bilateral mini-open technique was employed in the degenerative cases, depending on symptoms and signes. If unilateral symptoms--pathology was identified, screws and rod were implanted percutaneously on the side contralateral to the pathology. The segmental fusion between vertebral bodies was always assured by a cage and autologous bone. The presented trauma case involved combined AO type A2 and B fractures. The anterior column was strengthened with vertebral body stents filled with bone cement, the posterior column was fixed with a percutaneously implanted screw rod system. Insertion of stents in the collapsed vertebra significantly increased the vertebral body height and also improved the stability of the spine. Minimally invasive spine surgery techniques appear more advantageous over the traditional open spine surgery that necessitates for large midline approaches. PMID:23750428

  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. 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

  5. Effect of a Complex Lutein Formula in an Animal Model for Light-Induced Retinal Degeneration.

    PubMed

    Cheng, Yin-Pin; Ke, Chia-Ying; Kuo, Chih-Chieh; Lee, Yih-Jing

    2016-08-31

    Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure. PMID:27426260

  6. 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

  7. Cellular and 3D optical coherence tomography assessment during the initiation and progression of retinal degeneration in the Ccl2/Cx3cr1-deficient mouse.

    PubMed

    Zhou, Yongdong; Sheets, Kristopher G; Knott, Eric J; Regan, Cornelius E; Tuo, Jingsheng; Chan, Chi-Chao; Gordon, William C; Bazan, Nicolas G

    2011-11-01

    Retinal pathologies common to human eye diseases, including abnormal retinal pigment epithelial (RPE) cells, drusen-like accumulation, photoreceptor atrophy, and choroidal neovascularization, have been reported in the Ccl2/Cx3cr1-deficient mouse. The Ccl2 gene encodes the pro-inflammatory chemokine CCL2 (MCP-1), which is responsible for chemotactic recruitment of monocyte-derived macrophages to sites of inflammation. The Cx3cr1 gene encodes the fractalkine receptor, CX3CR1, and is required for accumulation of monocytes and microglia recruited via CCL2. Chemokine-mediated inflammation is implicated in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and uveoretinitis, and proper chemokine signaling from the RPE, Müller glia, and astrocytes is necessary to regulate leukocyte trafficking. Therefore, this mouse, possessing aberrant chemokine signaling coupled with retinal degenerative pathologies, presents an ideal opportunity to investigate the effect of altered signaling on retinal homeostasis and photoreceptor degeneration. Since this mouse is a recent development, more data covering the onset, location, and progression rate of pathologies is needed. In the present study we establish these parameters and show two photoreceptor cell death processes. Our observations of decreased glutamine synthetase and increased glial fibrillary acidic protein suggest that Müller cells respond very early within regions where lesions are forming. Finally, we suggest that retinal angiomatous proliferation contributes to pathological angiogenesis in this Ccl2/Cx3cr1-deficient mouse.

  8. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 11: interbody techniques for lumbar fusion.

    PubMed

    Mummaneni, Praveen V; Dhall, Sanjay S; Eck, Jason C; Groff, Michael W; Ghogawala, Zoher; Watters, William C; Dailey, Andrew T; Resnick, Daniel K; Choudhri, Tanvir F; Sharan, Alok; Wang, Jeffrey C; Kaiser, Michael G

    2014-07-01

    Interbody fusion techniques have been promoted as an adjunct to lumbar fusion procedures in an effort to enhance fusion rates and potentially improve clinical outcome. The medical evidence continues to suggest that interbody techniques are associated with higher fusion rates compared with posterolateral lumbar fusion (PLF) in patients with degenerative spondylolisthesis who demonstrate preoperative instability. There is no conclusive evidence demonstrating improved clinical or radiographic outcomes based on the different interbody fusion techniques. The addition of a PLF when posterior or anterior interbody lumbar fusion is performed remains an option, although due to increased cost and complications, it is not recommended. No substantial clinical benefit has been demonstrated when a PLF is included with an interbody fusion. For lumbar degenerative disc disease without instability, there is moderate evidence that the standalone anterior lumbar interbody fusion (ALIF) has better clinical outcomes than the ALIF plus instrumented, open PLF. With regard to type of interbody spacer used, frozen allograft is associated with lower pseudarthrosis rates compared with freeze-dried allograft; however, this was not associated with a difference in clinical outcome.

  9. The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson’s disease and other degenerative parkinsonisms

    PubMed Central

    Cannas, Antonino; Borghero, Giuseppe; Floris, Gian Luca; Solla, Paolo; Chiò, Adriano; Traynor, Bryan J.; Calvo, Andrea; Restagno, Gabriella; Majounie, Elisa; Costantino, Emanuela; Piras, Valeria; Lavra, Loredana; Pani, Carla; Orofino, Gianni; Di Stefano, Francesca; Tacconi, Paolo; Mascia, Marcello Mario; Muroni, Antonella; Murru, Maria Rita; Tranquilli, Stefania; Corongiu, Daniela; Rolesu, Marcella; Cuccu, Stefania; Marrosu, Francesco; Marrosu, Maria Giovanna

    2013-01-01

    Background Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie PD and/or other forms of degenerative parkinsonism on this Mediterranean island. Design We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases), and 604 unrelated controls for the c.1144G>A (p.A382T) missense mutation of the TARDBP gene. Results The p.A382T mutation was identified in 9 patients with parkinsonism. Of these, 5 (0.9% of PD patients) presented a typical PD (2 with familiar forms), while 4 patients (6.0% of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in 8 Sardinian controls (1.3%) consistent with a founder mutation in the island population. Conclusions Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD. PMID:23546887

  10. "To perpetuate blindness!": attitudes of UK patients with inherited retinal disease towards genetic testing.

    PubMed

    Potrata, Barbara; McKibbin, Martin; Lim, Jennifer Nw; Hewison, Jenny

    2014-07-01

    Availability and accuracy of genetic testing in ophthalmology has increased yet the benefits are unclear especially for those conditions where cure or treatments are limited. To explore attitudes to and patients' understanding of possible advantages and disadvantages of genetic testing for inherited retinal disease, we undertook focus groups in three West Yorkshire towns in the UK. Most of our participants had retinitis pigmentosa and one of the focus groups consisted of participants from (British) Asian ethnic background. Here, we report only those attitudes which were common in all three focus groups. Some of the attitudes have already been reported in the literature. Novel findings include attitudes held towards informed choice and life planning, particularly among more severely affected participants. For example, participants appreciated that genetic testing increases informed choice and enables life planning, but these understandings tended to be in a specific sense: informed choice whether to have children and family planning in order to prevent illness recurrence. We conclude that even though these patients are not a homogeneous group, their attitudes tend to be underpinned by deep anxiety of passing their visual impairment onto their children. In this respect, they differ importantly from a small minority of the deaf who would prefer to have children with hearing loss, and from the more general population who do not believe that blindness is a "severe" enough disability to warrant avoiding having children. PMID:24366860

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

    PubMed Central

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

    2015-01-01

    Abstract 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

  12. 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

  13. Assessment of Hereditary Retinal Degeneration in the English Springer Spaniel Dog and Disease Relationship to an RPGRIP1 Mutation

    PubMed Central

    Narfström, Kristina; Jeong, Manbok; Hyman, Jennifer; Madsen, Richard W.; Bergström, Tomas F.

    2012-01-01

    Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA), is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). Recent molecular studies in the English Springer Spaniel (ESS) dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG) is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention. PMID:22550515

  14. Clinical outcomes of lumbar degenerative disc disease treated with posterior lumbar interbody fusion allograft spacer: a prospective, multicenter trial with 2-year follow-up.

    PubMed

    Arnold, Paul M; Robbins, Stephen; Paullus, Wayne; Faust, Stephen; Holt, Richard; McGuire, Robert

    2009-07-01

    The clinical benefits and complications of posterior lumbar interbody fusion (PLIF) have been studied over the past 60 years. In recent years, spine surgeons have had the option of treating low back pain caused by degenerative disc disease using PLIF with machined allograft spacers and posterior pedicle fixation. The purpose of this clinical series was to assess the clinical benefits of using a machined PLIF allograft spacer and posterior pedicle fixation to treat degenerative disc disease, both in terms of fusion rates and patient outcomes, and to compare these results with those in previous studies using autograft and metal interbody fusion devices. Results were also compared with results from studies using transverse process fusion. This prospective, nonrandomized clinical series was conducted at 10 US medical centers. Eighty-nine (55 male, 34 female) patients underwent PLIF with a presized, machined allograft spacer and posterior pedicle fixation between January 2000 and April 2003. Their outcomes were compared with outcomes in previous series described in the literature. All patients had experienced at least 6 months of low back pain that had been unresponsive to nonsurgical treatment. Physical examinations were performed before surgery, after surgery, and at 4 follow-up visits (6 weeks, 6 months, 12 months, 24 months). At each interval, we obtained radiographs and patient outcome measures, including SF-36 Bodily Pain Score, visual analog scale pain rating, and Oswestry Disability Index. The primary outcome was fusion results at 12 and 24 months; the secondary outcomes were pain, disability, function/quality of life, and satisfaction. One-level PLIFs were performed in 65 patients, and 2-level PLIFs in 24 patients. Flexion-extension radiographs at 12 and 24 months revealed a 98% fusion rate. Of the 72 patients who reached the 12-month follow-up, 86% reported decreased pain and disability as measured with the Oswestry Disability Index. Decreased pain as measured

  15. 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

  16. 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

  17. 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

  18. Serum levels of BMP-2, 4, 7 and AHSG in patients with degenerative joint disease requiring total arthroplasty of the hip and temporomandibular joints.

    PubMed

    Albilia, Jonathan B; Tenenbaum, Howard C; Clokie, Cameron M L; Walt, David R; Baker, Gerald I; Psutka, David J; Backstein, David; Peel, Sean A F

    2013-01-01

    To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ≥8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

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

    PubMed Central

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

    2013-01-01

    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

  5. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 2: assessment of functional outcome following lumbar fusion.

    PubMed

    Ghogawala, Zoher; Resnick, Daniel K; Watters, William C; Mummaneni, Praveen V; Dailey, Andrew T; Choudhri, Tanvir F; Eck, Jason C; Sharan, Alok; Groff, Michael W; Wang, Jeffrey C; Dhall, Sanjay S; Kaiser, Michael G

    2014-07-01

    Assessment of functional patient-reported outcome following lumbar spinal fusion continues to be essential for comparing the effectiveness of different treatments for patients presenting with degenerative disease of the lumbar spine. When assessing functional outcome in patients being treated with lumbar spinal fusion, a reliable, valid, and responsive outcomes instrument such as the Oswestry Disability Index should be used. The SF-36 and the SF-12 have emerged as dominant measures of general health-related quality of life. Research has established the minimum clinically important difference for major functional outcomes measures, and this should be considered when assessing clinical outcome. The results of recent studies suggest that a patient's pretreatment psychological state is a major independent variable that affects the ability to detect change in functional outcome.

  6. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 5: correlation between radiographic outcome and function.

    PubMed

    Dhall, Sanjay S; Choudhri, Tanvir F; Eck, Jason C; Groff, Michael W; Ghogawala, Zoher; Watters, William C; Dailey, Andrew T; Resnick, Daniel K; Sharan, Alok; Mummaneni, Praveen V; Wang, Jeffrey C; Kaiser, Michael G

    2014-07-01

    In an effort to diminish pain or progressive instability, due to either the pathological process or as a result of surgical decompression, one of the primary goals of a fusion procedure is to achieve a solid arthrodesis. Assuming that pain and disability result from lost mechanical integrity of the spine, the objective of a fusion across an unstable segment is to eliminate pathological motion and improve clinical outcome. However, conclusive evidence of this correlation, between successful fusion and clinical outcome, remains elusive, and thus the necessity of documenting successful arthrodesis through radiographic analysis remains debatable. Although a definitive cause and effect relationship has not been demonstrated, there is moderate evidence that demonstrates a positive association between radiographic presence of fusion and improved clinical outcome. Due to this growing body of literature, it is recommended that strategies intended to enhance the potential for radiographic fusion are considered when performing a lumbar arthrodesis for degenerative spine disease.

  7. [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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Enhancing human nucleus pulposus cells for biological treatment approaches of degenerative intervertebral disc diseases: a systematic review.

    PubMed

    Mern, Demissew Shenegelegn; Beierfuß, Anja; Thomé, Claudius; Hegewald, Aldemar Andres

    2014-12-01

    Intervertebral disc (IVD) degeneration has been described as an aberrant, cell-mediated, age- and genetics-dependent molecular degeneration process, which can be accelerated by nutritional, mechanical and toxic factors. Collective involvement of these factors can result in structural failures, which are often associated with pain. Current treatment approaches are restricted to symptomatic therapies, not addressing options of restoring structural or biological deterioration of the IVD as the underlying problem. Therapeutic potentials of IVD cell transplantation, biomaterials, inhibiting or activating bioactive factors, including gene-therapeutic approaches, have been shown in vitro or in small animal models. Since human degenerative IVD cells display distinctive features with regard to cell biology and regenerative potential, we attempted a systematic review, investigating the in vitro response of human nucleus pulposus cells to different stimuli. Therefore, we conducted an electronic database search on Medline through July 2011 to identify, compare and discuss publications concerning the effects of cell-cell stimulation, bioactive factors, biomaterials and combinations thereof in terms of cell isolation, proliferation, differentiation and matrix protein synthesis. This survey and discussion might serve as a source for designing future biological treatment strategies for the human IVD.

  13. Contralateral interlaminar approach for intraforaminal lumbar degenerative disease with special emphasis on L5-S1 level: A technical note

    PubMed Central

    Zekaj, Edvin; Menghetti, Claudia; Saleh, Christian; Isidori, Alessandra; Bona, Alberto R.; Aimar, Enrico; Servello, Domenico

    2016-01-01

    Background: Intraforaminal disc herniations at the L5-S1 level are extremely surgically challenging lesions. Intracanal approaches frequently require partial or total facetectomy, which may lead to instability. Solely extraforaminal approaches may offer limited visualization of the more medial superiorly exiting and inferiorly exiting nerve roots; this approach is also more complicated at L5-S1 due to the often large L5 transverse process and the iliac wing. Methods: Nine patients with intraforaminal L5-S1 disc herniations, foraminal stenosis, or synovial cysts underwent contralateral interlaminar approaches for lesion resection. Preoperative and postoperative visual analog scale scores were evaluated, and complications were reviewed. Results: All 9 patients demonstrated immediate postoperative clinical improvement. None of the patients exhibited complications and none developed instability or neuropathic disorders. Conclusions: Although the number of cases in our sample was very small (9 in total), the contralateral interlaminar approach appeared to effectively address multiple degenerative L5-S1 foraminal pathologies. Large studies are needed to further evaluate the pros and cons of this approach. PMID:27713854

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Line bisection in Parkinson's disease: investigation of contributions of visual field, retinal vision, and scanning patterns to visuospatial function.

    PubMed

    Laudate, Thomas M; Neargarder, Sandy; Cronin-Golomb, Alice

    2013-04-01

    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.

  19. 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

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

    PubMed

    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; Ambrósio, António F

    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.

  1. Hybrid vitronectin-mimicking polycaprolactone scaffolds for human retinal progenitor cell differentiation and transplantation.

    PubMed

    Lawley, Elodie; Baranov, Petr; Young, Michael

    2015-01-01

    Many advances have been made in an attempt to treat retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. The irreversible loss of photoreceptors is common to both, and currently no restorative clinical treatment exists. It has been shown that retinal progenitor and photoreceptor precursor cell transplantation can rescue the retinal structure and function. Importantly, retinal progenitor cells can be collected from the developing neural retina with further expansion and additional modification in vitro, and the delivery into the degenerative host can be performed as a single-cell suspension injection or as a complex graft transplantation. Previously, we have described several polymer scaffolds for culture and transplantation of retinal progenitor cells of both mouse and human origin. This tissue engineering strategy increases donor cell survival and integration. We have also shown that biodegradable poly(ɛ-caprolactone) induces mature photoreceptor differentiation from human retinal progenitor cells. However, poor adhesive properties limit its use, and therefore it requires additional surface modification. The aim of this work was to study vitronectin-mimicking oligopeptides (Synthemax II-SC) poly(ɛ-caprolactone) films and their effects on human retinal progenitor cell adhesion, proliferation, and differentiation. Here, we show that the incorporation of vitronectin-mimicking oligopeptide into poly(ɛ-caprolactone) leads to dose-dependent increases in cell adhesion; the optimum dose identified as 30 µg/ml. Inhibition of human retinal progenitor cells proliferation was seen on poly(ɛ-caprolactone) and was maintained with the hybrid scaffold. This has been shown to be beneficial for driving cell differentiation. Additionally, we observed equal expression of Nrl, rhodopsin, recoverin, and rod outer membrane 1 after differentiation on the hybrid scaffold as compared to the standard fibronectin coating of poly

  2. 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.

  3. Photovoltaic retinal prosthesis: implant fabrication and performance.

    PubMed

    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.

  4. New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review

    PubMed Central

    Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

    2015-01-01

    The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments ‘on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice. PMID:26113499

  5. 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.

  6. [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

  7. 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

  8. 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.

  9. 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

  10. Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer's disease

    PubMed Central

    Polo, V; Garcia-Martin, E; Bambo, M P; Pinilla, J; Larrosa, J M; Satue, M; Otin, S; Pablo, L E

    2014-01-01

    Background To evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer's disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects. Methods AD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed. Results Retinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration. Conclusions Fourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration. PMID:24625377

  11. Veterinary Medicine and Multi-Omics Research for Future Nutrition Targets: Metabolomics and Transcriptomics of the Common Degenerative Mitral Valve Disease in Dogs.

    PubMed

    Li, Qinghong; Freeman, Lisa M; Rush, John E; Huggins, Gordon S; Kennedy, Adam D; Labuda, Jeffrey A; Laflamme, Dorothy P; Hannah, Steven S

    2015-08-01

    Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences.

  12. 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

  13. 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

  14. 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

  15. Early retinal function deficit without prominent morphological changes in the R6/2 mouse model of Huntington's disease.

    PubMed

    Ragauskas, Symantas; Leinonen, Henri; Puranen, Jooseppi; Rönkkö, Seppo; Nymark, Soile; Gurevicius, Kestutis; Lipponen, Arto; Kontkanen, Outi; Puoliväli, Jukka; Tanila, Heikki; Kalesnykas, Giedrius

    2014-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder that primarily affects the medium-size GABAergic neurons of striatum. The R6/2 mouse line is one of the most widely used animal models of HD. Previously the hallmarks of HD-related pathology have been detected in photoreceptors and interneurons of R6/2 mouse retina. Here we aimed to explore the survival of retinal ganglion cells (RGCs) and functional integrity of distinct retinal cell populations in R6/2 mice. The pattern electroretinography (PERG) signal was lost at the age of 8 weeks in R6/2 mice in contrast to the situation in wild-type (WT) littermates. This defect may be attributable to a major reduction in photopic ERG responses in R6/2 mice which was more evident in b- than a-wave amplitudes. At the age of 4 weeks R6/2 mice had predominantly the soluble form of mutant huntingtin protein (mHtt) in the RGC layer cells, whereas the aggregated form of mHtt was found in the majority of those cells from the 12-week-old R6/2 mice and onwards. Retinal astrocytes did not contain mHtt deposits. The total numbers of RGC layer cells, retinal astrocytes as well as optic nerve axons did not differ between 18-week-old R6/2 mice and their WT controls. Our data indicate that mHtt deposition does not cause RGC degeneration or retinal astrocyte loss in R6/2 mice even at a late stage of HD-related pathology. However, due to functional deficits in the rod- and cone-pathways, the R6/2 mice suffer progressive deficits in visual capabilities starting as early as 4 weeks; at 8 weeks there is severe impairment. This should be taken into account in any behavioral testing conducted in R6/2 mice. PMID:25469887

  16. 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

  17. 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.

  18. Age and disease-related structural changes in the retinal pigment epithelium

    PubMed Central

    Bonilha, Vera L

    2008-01-01

    As the retinal pigment epithelium (RPE) ages, a number of structural changes occur, including loss of melanin granules, increase in the density of residual bodies, accumulation of lipofuscin, accumulation of basal deposits on or within Bruch’s membrane, formation of drusen (between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane), thickening of Bruch’s membrane, microvilli atrophy and disorganization of the basal infoldings. Although these changes are well known, the basic mechanisms involved in them are frequently poorly understood. These age-related changes progress slowly and vary in severity in different individuals. These changes are also found in age-related macular degeneration (AMD), a late onset disease that severely impacts the RPE, but they are much more pronounced than during normal aging. However, the changes in AMD lead to severe loss of vision. Given the many supporting functions which the RPE serves for the retina, it is important to decipher the age-related changes in this epithelium in order to understand age-related changes in vision. PMID:19668732

  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. Topographic optic disc analysis by Heidelberg retinal tomography in ocular Behçet's disease

    PubMed Central

    Berker, Nilufer; Elgin, Ufuk; Ozdal, Pinar; Batman, Aygen; Soykan, Emel; Ozkan, Seyhan S

    2007-01-01

    Aim To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). Methods This prospective study included 47 eyes of 47 patients with ocular BD who were being followed‐up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non‐parametric Mann‐Whitney U test. Results The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup‐to‐disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). Conclusion A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs. PMID:17475703

  1. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

    PubMed Central

    Yan, Naihong; Cheng, Lin; Cho, Kinsang; Malik, Muhammad Taimur A.; Xiao, Lirong; Guo, Chenying; Yu, Honghua; Zhu, Ruilin; Rao, Rajesh C.; Chen, Dong Feng

    2016-01-01

    Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy. PMID:27677711

  2. Retinal macroglia changes in a triple transgenic mouse model of Alzheimer’s disease

    PubMed Central

    Edwards, Malia M.; Rodríguez, José J.; Lanza, Raquel Gutierrez; Yates, Joseph; Verkhratsky, Alexei; Lutty, Gerard A.

    2014-01-01

    The retinas of Alzheimer’s disease (AD) patients and transgenic AD animal models display amyloid beta deposits and degeneration of ganglion cells. Little is known, however, about the glial changes in the AD retina. The present study used a triple transgenic mouse model (3xTG-AD), which carries mutated human amyloid precursor protein, tau, and presenilin 1 genes and closely mimics the human brain pathology, to investigate retinal glial changes in AD. AD cognitive symptoms are known to begin in the 3xTG-AD mice at four months of age but plaques and tangles are not seen until six to twelve months. Müller cells in 3xTG-AD animals were GFAP-positive, indicating activation, at the earliest time point investigated, nine months. Astrocyte activation was also suggested in the 3xTG-AD mice by an apparent increase in size and process number. Another glial marker, S100, was expressed by astrocytes in both the non-transgenic (NTG) controls and 3xTG-AD retinas. Labeling was predominantly nuclear in nine month non-transgenic (NTG) control mice but was also seen in the cytoplasm and processes at 18 months of age. Interestingly, the nuclear localization was not as prominent in the 3xTG-AD retina even at nine months with labeling observed in astrocyte processes. The diffusion of S100 suggests the possible secretion of this protein, as is seen in the brain, with age and, more profoundly, associated with AD. Several dense, abnormally shaped, opaque structures were noted in all 3xTG-AD mice investigated. These structures, which were enveloped by GFAP and S100-positive astrocytes and Müller cells, were positive for amyloid beta, suggesting that they are amyloid plaques. Staining control retinas with amyloid showed similar structures in 30% of NTG animals but these were fewer in number and not associated with glial activation. The results herein indicate retinal glia activation in the 3xTG-AD mouse retina. PMID:25149907

  3. Retinal pigment epithelial cell proliferation

    PubMed Central

    Temple, Sally

    2015-01-01

    The human retinal pigment epithelium forms early in development and subsequently remains dormant, undergoing minimal proliferation throughout normal life. Retinal pigment epithelium proliferation, however, can be activated in disease states or by removing retinal pigment epithelial cells into culture. We review the conditions that control retinal pigment epithelial proliferation in culture, in animal models and in human disease and interpret retinal pigment epithelium proliferation in context of the recently discovered retinal pigment epithelium stem cell that is responsible for most in vitro retinal pigment epithelial proliferation. Retinal pigment epithelial proliferation-mediated wound repair that occurs in selected macular diseases is contrasted with retinal pigment epithelial proliferation-mediated fibroblastic scar formation that underlies proliferative vitreoretinopathy. We discuss the role of retinal pigment epithelial proliferation in age-related macular degeneration which is reparative in some cases and destructive in others. Macular retinal pigment epithelium wound repair and regression of choroidal neovascularization are more pronounced in younger than older patients. We discuss the possibility that the limited retinal pigment epithelial proliferation and latent wound repair in older age-related macular degeneration patients can be stimulated to promote disease regression in age-related macular degeneration. PMID:26041390

  4. Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy.

    PubMed

    Greenlee, M Heather West; Smith, Jodi D; Platt, Ekundayo M; Juarez, Jessica R; Timms, Leo L; Greenlee, Justin J

    2015-01-01

    Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.

  5. 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

  6. Retinal dystrophies, genomic applications in diagnosis and prospects for therapy

    PubMed Central

    Nash, Benjamin M.; Wright, Dale C.; Grigg, John R.; Bennetts, Bruce

    2015-01-01

    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

  7. 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.

  8. Non-diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship.

    PubMed

    Prakash, J; Gupta, T; Prakash, S; Bhushan, P; Usha; Sivasankar, M; Singh, S P

    2015-01-01

    Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Non-diabetic renal disease (NDRD), is known to occur in diabetic patients. The renal and retinal relationship in type 2 diabetes mellitus (T2DM) with nephropathy is not uniform. This study was carried to study the histological spectrum of nephropathy in type 2 diabetic patients with proteinuria and its relationship with diabetic retinopathy (DR). Total 31 (males - 26; females - 5) proteinuric type 2 diabetic patients were studied. Average age of patients was 50.7 years. Nephrotic syndrome was noted in 21 (67.7%) patients. Overall, isolated DN, NDRD and NDRD superimposed on DN (mixed lesion) were observed in 12 (38.7%), 13 (41.9%) and 6 (19.4%) cases, respectively. DR was absent in 21/31 (67.7%) cases. The spectrum of nephropathy in patients without DR included: DN in 6 (28.57%), NDRD in 12 (57.14%) and mixed lesion in 3 (14.29%). Kidney histology in patients with DR (n-10) revealed DN in 6 (60%), NDRD in 1 (10%) and mixed lesion in 3 (30%) patients. Thus, absence of DR favors NDRD but does not exclude DN because isolated DN was noted in 28.57% cases in absence of DR. Similarly biopsy proven NDRD (pure NDRD; 10% and mixed lesion; 30%) was noted in 40% of cases in presence of DR. In summary, patients with T2DM had higher incidence of NDRD. DR is less frequent (32.3%) in type 2 diabetes and is a poor predictor of type of nephropathy. Hence, renal biopsy is essential for precise diagnosis of nephropathy in patients with T2DM.

  9. Non-diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship

    PubMed Central

    Prakash, J.; Gupta, T.; Prakash, S.; Bhushan, P.; Usha; Sivasankar, M.; Singh, S. P.

    2015-01-01

    Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Non-diabetic renal disease (NDRD), is known to occur in diabetic patients. The renal and retinal relationship in type 2 diabetes mellitus (T2DM) with nephropathy is not uniform. This study was carried to study the histological spectrum of nephropathy in type 2 diabetic patients with proteinuria and its relationship with diabetic retinopathy (DR). Total 31 (males - 26; females - 5) proteinuric type 2 diabetic patients were studied. Average age of patients was 50.7 years. Nephrotic syndrome was noted in 21 (67.7%) patients. Overall, isolated DN, NDRD and NDRD superimposed on DN (mixed lesion) were observed in 12 (38.7%), 13 (41.9%) and 6 (19.4%) cases, respectively. DR was absent in 21/31 (67.7%) cases. The spectrum of nephropathy in patients without DR included: DN in 6 (28.57%), NDRD in 12 (57.14%) and mixed lesion in 3 (14.29%). Kidney histology in patients with DR (n-10) revealed DN in 6 (60%), NDRD in 1 (10%) and mixed lesion in 3 (30%) patients. Thus, absence of DR favors NDRD but does not exclude DN because isolated DN was noted in 28.57% cases in absence of DR. Similarly biopsy proven NDRD (pure NDRD; 10% and mixed lesion; 30%) was noted in 40% of cases in presence of DR. In summary, patients with T2DM had higher incidence of NDRD. DR is less frequent (32.3%) in type 2 diabetes and is a poor predictor of type of nephropathy. Hence, renal biopsy is essential for precise diagnosis of nephropathy in patients with T2DM. PMID:26199473

  10. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 14: brace therapy as an adjunct to or substitute for lumbar fusion.

    PubMed

    Dailey, Andrew T; Ghogawala, Zoher; Choudhri, Tanvir F; Watters, William C; Resnick, Daniel K; Sharan, Alok; Eck, Jason C; Mummaneni, Praveen V; Wang, Jeffrey C; Groff, Michael W; Dhall, Sanjay S; Kaiser, Michael G

    2014-07-01

    The utilization of orthotic devices for lumbar degenerative disease has been justified from both a prognostic and therapeutic perspective. As a prognostic tool, bracing is applied prior to surgery to determine if immobilization of the spine leads to symptomatic relief and thus justify the performance of a fusion. Since bracing does not eliminate motion, the validity of this assumption is questionable. Only one low-level study has investigated the predictive value of bracing prior to surgery. No correlation between response to bracing and fusion outcome was observed; therefore a trial of preoperative bracing is not recommended. Based on low-level evidence, the use of bracing is not recommended for the prevention of low-back pain in a general working population, since the incidence of low-back pain and impact on productivity were not reduced. However, in laborers with a history of back pain, a positive impact on lost workdays was observed when bracing was applied. Bracing is recommended as an option for treatment of subacute low-back pain, as several higher-level studies have demonstrated an improvement in pain scores and function. The use of bracing following instrumented posterolateral fusion, however, is not recommended, since equivalent outcomes have been demonstrated with or without the application of a brace. PMID:24980591

  11. Posterior Transpedicular Dynamic Stabilization versus Total Disc Replacement in the Treatment of Lumbar Painful Degenerative Disc Disease: A Comparison of Clinical Results

    PubMed Central

    Oktenoglu, Tunc; Ozer, Ali Fahir; Sasani, Mehdi; Ataker, Yaprak; Gomleksiz, Cengiz; Celebi, Irfan

    2013-01-01

    Study Design. Prospective clinical study. Objective. This study compares the clinical results of anterior lumbar total disc replacement and posterior transpedicular dynamic stabilization in the treatment of degenerative disc disease. Summary and Background Data. Over the last two decades, both techniques have emerged as alternative treatment options to fusion surgery. Methods. This study was conducted between 2004 and 2010 with a total of 50 patients (25 in each group). The mean age of the patients in total disc prosthesis group was 37,32 years. The mean age of the patients in posterior dynamic transpedicular stabilization was 43,08. Clinical (VAS and Oswestry) and radiological evaluations (lumbar lordosis and segmental lordosis angles) of the patients were carried out prior to the operation and 3, 12, and 24 months after the operation. We compared the average duration of surgery, blood loss during the surgery and the length of hospital stay of both groups. Results. Both techniques offered significant improvements in clinical parameters. There was no significant change in radiologic evaluations after the surgery for both techniques. Conclusion. Both dynamic systems provided spine stability. However, the posterior dynamic system had a slight advantage over anterior disc prosthesis because of its convenient application and fewer possible complications. PMID:23401784

  12. 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

  13. Segmental mobility, disc height and patient-reported outcomes after surgery for degenerative disc disease: a prospective randomised trial comparing disc replacement and multidisciplinary rehabilitation.

    PubMed

    Johnsen, L G; Brinckmann, P; Hellum, C; Rossvoll, I; Leivseth, G

    2013-01-01

    This prospective multicentre study was undertaken to determine segmental movement, disc height and sagittal alignment after total disc replacement (TDR) in the lumbosacral spine and to assess the correlation of biomechanical properties to clinical outcomes.A total of 173 patients with degenerative disc disease and low back pain for more than one year were randomised to receive either TDR or multidisciplinary rehabilitation (MDR). Segmental movement in the sagittal plane and disc height were measured using distortion compensated roentgen analysis (DCRA) comparing radiographs in active flexion and extension. Correlation analysis between the range of movement or disc height and patient-reported outcomes was performed in both groups. After two years, no significant change in movement in the sagittal plane was found in segments with TDR or between the two treatment groups. It remained the same or increased slightly in untreated segments in the TDR group and in this group there was a significant increase in disc height in the operated segments. There was no correlation between segmental movement or disc height and patient-reported outcomes in either group.In this study, insertion of an intervertebral disc prosthesis TDR did not increase movement in the sagittal plane and segmental movement did not correlate with patient-reported outcomes. This suggests that in the lumbar spine the movement preserving properties of TDR are not major determinants of clinical outcomes.

  14. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 14: brace therapy as an adjunct to or substitute for lumbar fusion.

    PubMed

    Dailey, Andrew T; Ghogawala, Zoher; Choudhri, Tanvir F; Watters, William C; Resnick, Daniel K; Sharan, Alok; Eck, Jason C; Mummaneni, Praveen V; Wang, Jeffrey C; Groff, Michael W; Dhall, Sanjay S; Kaiser, Michael G

    2014-07-01

    The utilization of orthotic devices for lumbar degenerative disease has been justified from both a prognostic and therapeutic perspective. As a prognostic tool, bracing is applied prior to surgery to determine if immobilization of the spine leads to symptomatic relief and thus justify the performance of a fusion. Since bracing does not eliminate motion, the validity of this assumption is questionable. Only one low-level study has investigated the predictive value of bracing prior to surgery. No correlation between response to bracing and fusion outcome was observed; therefore a trial of preoperative bracing is not recommended. Based on low-level evidence, the use of bracing is not recommended for the prevention of low-back pain in a general working population, since the incidence of low-back pain and impact on productivity were not reduced. However, in laborers with a history of back pain, a positive impact on lost workdays was observed when bracing was applied. Bracing is recommended as an option for treatment of subacute low-back pain, as several higher-level studies have demonstrated an improvement in pain scores and function. The use of bracing following instrumented posterolateral fusion, however, is not recommended, since equivalent outcomes have been demonstrated with or without the application of a brace.

  15. 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

    2015-07-31

    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.

  16. Degenerative alterations of the cementum-periodontal ligament complex and early tooth loss in a young patient with periodontal disease.

    PubMed

    Petruţiu, S A; Buiga, Petronela; Roman, Alexandra; Danciu, Theodora; Mihu, Carmen Mihaela; Mihu, D

    2012-01-01

    Premature exfoliation of primary or permanent teeth in children or adolescents is extremely rare and it can be a manifestation of an underlying systemic disease. This study aims to present the histological aspects associated with early tooth loss in a case of periodontal disease developed without local inflammation and with minimal periodontal pockets and attachment loss. The maxillary left second premolar was extracted together with a gingival collar attached to the root surface. The histological analysis recorded the resorption of the cementum in multiple areas of the entire root surface with the connective tissue of the desmodontium invading the lacunae defects. The connective tissue rich in cells occupied the periodontal ligamentar space and the resorptive areas. No inflammation was obvious in the periodontal ligament connective tissue. This report may warn clinicians about the possibility of the association of cemental abnormalities with early tooth loss.

  17. Deletion of RBP-J in adult mice leads to the onset of aortic valve degenerative diseases.

    PubMed

    Li, Zhi; Feng, Lei; Wang, Chun-Mei; Zheng, Qi-Jun; Zhao, Bi-Jun; Yi, Wei; Zhang, Jin-Zhou; Wang, Yue-Min; Guo, Hai-Tao; Yi, Ding-Hua; Han, Hua

    2012-04-01

    Transcription factor RBP-J-mediated Notch signaling has been implicated in several inherited cardiovascular diseases including aortic valve diseases (AVD). But whether Notch signal plays a role in AVD in adults has been unclear. This study aims to test whether the deletion of RBP-J in adult mice would lead to AVD and to investigate the underlying mechanisms. Cre-LoxP-mediated gene deletion was employed to disrupt Notch signal in adult mice. Immunofluorescence and electron microscope observations showed that deletion of RBP-J in adult mice led to early morphological changes of AVD. The size of aortic valve was enlarged. The endothelial homeostasis was perturbed, probably due to the up-regulation of VEGFR2. The endothelial cells exhibited increased proliferation and loose endothelial junctions. The valvular mesenchyme displayed significant fibrosis, consistent with the up-regulation of TGF-β1 and activation of endothelial-mesenchymal transition. We observed melanin-producing cells in aortic valves. The number of melanin-producing cells increased significantly, and their location changed from the mesenchyme to subendothelial layer of valve cusps in RBP-J deficient mice. These results suggest that RBP-J-mediated Notch signaling in aortic valves may be critically involved in valve homeostasis and valve diseases as well. These findings will be helpful for the understanding of the molecular mechanisms of AVD in adults.

  18. Modern retinal laser therapy.

    PubMed

    Kozak, Igor; Luttrull, Jeffrey K

    2015-01-01

    Medicinal lasers are a standard source of light to produce retinal tissue photocoagulation to treat retinovascular disease. The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study were large randomized clinical trials that have shown beneficial effect of retinal laser photocoagulation in diabetic retinopathy and have dictated the standard of care for decades. However, current treatment protocols undergo modifications. Types of lasers used in treatment of retinal diseases include argon, diode, dye and multicolor lasers, micropulse lasers and lasers for photodynamic therapy. Delivery systems include contact lens slit-lamp laser delivery, indirect ophthalmocope based laser photocoagulation and camera based navigated retinal photocoagulation with retinal eye-tracking. Selective targeted photocoagulation could be a future alternative to panretinal photocoagulation. PMID:25892934

  19. 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

  20. 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

  1. 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

  2. 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

  3. Computer-aided diagnosis of plus disease via measurement of vessel thickness in retinal fundus images of preterm infants.

    PubMed

    Oloumi, Faraz; Rangayyan, Rangaraj M; Casti, Paola; Ells, Anna L

    2015-11-01

    Changes in the characteristics of retinal vessels such as width and tortuosity can be signs of the presence of several diseases such retinopathy of prematurity (ROP) and diabetic retinopathy. Plus disease is an indicator of ROP which requires treatment and is signified by an increase in posterior venular width. In this work, we present image processing techniques for the detection, segmentation, tracking, and measurement of the width of the major temporal arcade (MTA), which is the thickest venular branch in the retina. Several image processing techniques have been employed, including the use of Gabor filters to detect the MTA, morphological image processing to obtain its skeleton, Canny's method to detect and select MTA vessel-edge candidates, least-squares fitting to interpolate the MTA edges, and geometrical procedures to measure the width of the MTA. The results, obtained using 110 retinal fundus images of preterm infants, indicate a statistically highly significant difference in MTA width of normal cases as compared to cases with plus disease (p<0.01). The results provide good accuracy in computer-aided diagnosis (CAD) of plus disease with an area under the receiver operating characteristic curve of 0.76. The proposed methods may be used in CAD of plus disease and timely treatment of ROP in a clinical or teleophthalmological setting.

  4. Multifunctional PEG Retinylamine Conjugate Provides Prolonged Protection against Retinal Degeneration in Mice

    PubMed Central

    2015-01-01

    A polyethylene glycol (PEG) retinylamine (Ret-NH2) conjugate PEG-GFL-NH-Ret with a glycine-phenylalanine-leucine (GFL) spacer was synthesized for controlled oral delivery of Ret-NH2 to treat retinal degenerative diseases, including Stargardt disease (STGD) and age-related macular degeneration (AMD). The peptide spacer was introduced for sustained release of the drug by digestive enzymes in the gastrointestinal tract. The pharmacokinetics experiments showed that the PEG conjugate could control the sustained drug release after oral administration and had much lower nonspecific liver drug accumulation than the free drug in wild-type female C57BL mice. In the mean time, the conjugate maintained the same concentration of Ret-NH2 in the eye as the free drug. Also, PEG-GFL-NH-Ret at a Ret-NH2 equivalent dose of 25 mg/kg produced complete protection of Abca4–/–Rdh8–/– mouse retinas against light-induced retinal degeneration for 3 days after oral administration, as revealed by OCT retina imaging, whereas free Ret-NH2 did not provide any protection under identical conditions. The polymer conjugate PEG-GFL-NH-Ret has great potential for controlled delivery of Ret-NH2 to the eye for effective protection against retinal degenerative diseases. PMID:25390360

  5. Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.

    PubMed

    He, Chang; Zhao, Chen; Kumar, Anil; Lee, Chunsik; Chen, Mingquan; Huang, Lijuan; Wang, Jing; Ren, Xiangrong; Jiang, Yida; Chen, Wei; Wang, Bin; Gao, Zhiqin; Zhong, Zheng; Huang, Zijing; Zhang, Fan; Huang, Bing; Ding, Hao; Ju, Rong; Tang, Zhongshu; Liu, Yizhi; Cao, Yihai; Li, Xuri; Liu, Xialin

    2014-10-14

    Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.

  6. Multifunctional PEG retinylamine conjugate provides prolonged protection against retinal degeneration in mice.

    PubMed

    Yu, Guanping; Wu, Xueming; Ayat, Nadia; Maeda, Akiko; Gao, Song-Qi; Golczak, Marcin; Palczewski, Krzysztof; Lu, Zheng-Rong

    2014-12-01

    A polyethylene glycol (PEG) retinylamine (Ret-NH2) conjugate PEG-GFL-NH-Ret with a glycine-phenylalanine-leucine (GFL) spacer was synthesized for controlled oral delivery of Ret-NH2 to treat retinal degenerative diseases, including Stargardt disease (STGD) and age-related macular degeneration (AMD). The peptide spacer was introduced for sustained release of the drug by digestive enzymes in the gastrointestinal tract. The pharmacokinetics experiments showed that the PEG conjugate could control the sustained drug release after oral administration and had much lower nonspecific liver drug accumulation than the free drug in wild-type female C57BL mice. In the mean time, the conjugate maintained the same concentration of Ret-NH2 in the eye as the free drug. Also, PEG-GFL-NH-Ret at a Ret-NH2 equivalent dose of 25 mg/kg produced complete protection of Abca4(-/-)Rdh8(-/-) mouse retinas against light-induced retinal degeneration for 3 days after oral administration, as revealed by OCT retina imaging, whereas free Ret-NH2 did not provide any protection under identical conditions. The polymer conjugate PEG-GFL-NH-Ret has great potential for controlled delivery of Ret-NH2 to the eye for effective protection against retinal degenerative diseases.

  7. [Clinical associations between retinal vascular diseases and cardiovascular diseases in patients with systemic atheromatosis].

    PubMed

    Stefănescu-Dima, Alin; Bătăiosu, Constantin; Sas, Teodor; Puianu, Mihaela

    2013-01-01

    A clinical study was conducted on a sample of 48 patients examined within 3 months. Of these, 27 patients were recruited by ophtalmologic criteria and 21 recruited by cardiologic criteria, 25% of these patients coming for routine check. They were investigated by ophthalmic examination, cardiological examination, imaging and laboratory examination. Testing has shown a strong link between cardiovascular disease and the eye of the patients investigated. The study demonstrated the need for interdisciplinary consultation for patients with vascular complaints in the carotid territory and a close correlation between the vascular and ophthalmologic pathology at this level.

  8. Quantitative Genetic Analysis of Retinal Degeneration in the Blind Cavefish Astyanax mexicanus

    PubMed Central

    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 F2 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

  9. Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged Mice: An Immunohistochemical Study.

    PubMed

    Kim, Chan-Sik; Park, Sok; Chun, Yoonseok; Song, Wook; Kim, Hee-Jae; Kim, Junghyun

    2015-01-01

    In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control). Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks). The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress. PMID:26404251

  10. 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

  11. 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

  12. 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

  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. Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

    PubMed Central

    2013-01-01

    Background Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains. PMID:23586671

  15. Induced pluripotent stem cells as custom therapeutics for retinal repair: progress and rationale.

    PubMed

    Wright, Lynda S; Phillips, M Joseph; Pinilla, Isabel; Hei, Derek; Gamm, David M

    2014-06-01

    Human pluripotent stem cells have made a remarkable impact on science, technology and medicine by providing a potentially unlimited source of human cells for basic research and clinical applications. In recent years, knowledge gained from the study of human embryonic stem cells and mammalian somatic cell reprogramming has led to the routine production of human induced pluripotent stem cells (hiPSCs) in laboratories worldwide. hiPSCs show promise for use in transplantation, high throughput drug screening, "disease-in-a-dish" modeling, disease gene discovery, and gene therapy testing. This review will focus on the first application, beginning with a discussion of methods for producing retinal lineage cells that are lost in inherited and acquired forms of retinal degenerative disease. The selection of appropriate hiPSC-derived donor cell type(s) for transplantation will be discussed, as will the caveats and prerequisite steps to formulating a clinical Good Manufacturing Practice (cGMP) product for clinical trials.

  16. 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

  17. Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

    PubMed

    Rah, HyungChul; Maggs, David J; Lyons, Leslie A

    2006-10-01

    An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Methylnitrosourea (MNU)-induced Retinal Degeneration and Regeneration in the Zebrafish: Histological and Functional Characteristics

    PubMed Central

    Maurer, Ellinor; Tschopp, Markus; Tappeiner, Christoph; Sallin, Pauline; Jazwinska, Anna; Enzmann, Volker

    2014-01-01

    Retinal degenerative diseases, e.g. retinitis pigmentosa, with resulting photoreceptor damage account for the majority of vision loss in the industrial world. Animal models are of pivotal importance to study such diseases. In this regard the photoreceptor-specific toxin N-methyl-N-nitrosourea (MNU) has been widely used in rodents to pharmacologically induce retinal degeneration. Previously, we have established a MNU-induced retinal degeneration model in the zebrafish, another popular model system in visual research. A fascinating difference to mammals is the persistent neurogenesis in the adult zebrafish retina and its regeneration after damage. To quantify this observation we have employed visual acuity measurements in the adult zebrafish. Thereby, the optokinetic reflex was used to follow functional changes in non-anesthetized fish. This was supplemented with histology as well as immunohistochemical staining for apoptosis (TUNEL) and proliferation (PCNA) to correlate the developing morphological changes. In summary, apoptosis of photoreceptors occurs three days after MNU treatment, which is followed by a marked reduction of cells in the outer nuclear layer (ONL). Thereafter, proliferation of cells in the inner nuclear layer (INL) and ONL is observed. Herein, we reveal that not only a complete histological but also a functional regeneration occurs over a time course of 30 days. Now we illustrate the methods to quantify and follow up zebrafish retinal de- and regeneration using MNU in a video-format. PMID:25350292

  3. 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

  4. 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

  5. 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)

  6. 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

  7. [Actualities regarding the degenerative valvular heart].

    PubMed

    Ionescu, Simona Daniela; Sandru, V; Burdujan, Alina

    2002-01-01

    The degenerative valvular heart disease became prioritary from the epidemiological point of view by contrast with the rheumatismal one, as a consequence of the increase of the economic standard and of average life expectancy. The calcific aortic stenosis is the most frequently encountered among the valvular heart lesions. Since the history of this disease is not well known, many efforts have been made in order to research all its aspects from the etiology to therapeutical and prophylactic methods.

  8. 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

  9. Evaluating retinal ganglion cell loss and dysfunction.

    PubMed

    Mead, Ben; Tomarev, Stanislav

    2016-10-01

    Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity.

  10. Systolic arterial blood pressure in small-breed dogs with degenerative mitral valve disease: a prospective study of 103 cases (2007-2012).

    PubMed

    Petit, A M; Gouni, V; Tissier, R; Trehiou-Sechi, E; Misbach, C; Pouchelon, J-L; Lefebvre, H P; Chetboul, V

    2013-09-01

    The objective of this prospective observational study was to assess systolic arterial blood pressure (SABP) in small-breed dogs with degenerative mitral valve disease (MVD) from different International Small Animal Cardiac Health Council (ISACHC) heart failure classes. For this purpose, 103 client-owned dogs weighing <20 kg (mean ± standard deviation, 8.5 ± 3.0 kg; aged 9.8 ± 2.9 years) and presenting with MVD diagnosed by echo-Doppler examination were enrolled. Nineteen healthy dogs (9.9 ± 2.3 years; 8.7 ± 4.2 kg) were concurrently recruited as controls. SABP was measured in unsedated dogs using the Doppler method according to the recommendations in the American College of Veterinary Medicine consensus statement. SABP was significantly increased in dogs in ISACHC class 1 (n=53; median, interquartile range 140 mmHg, 130-150 mmHg) and class 2 (n=21; 140 mmHg, 130-150 mmHg), compared to the control group (n=19; 130 mmHg, 120-140 mmHg; P<0.01 and P<0.05, respectively), but remained within the reference interval (≤ 160 mmHg). Conversely, dogs in ISACHC class 3 showed a significantly lower SABP (n=29, 120 mmHg, 110-130 mmHg) than those from all other ISACHC classes (P<0.001) and the controls (P<0.05). Additionally, SABP<120 mmHg was recorded in 13/103 dogs (13%). The 13 dogs were all ISACHC class 3 (3a or 3b) and were under medical treatment for heart failure. In conclusion, MVD was often associated with SABP values that were within the reference interval, but at its upper end. However, a significant decrease in SABP was observed in dogs with ISACHC heart failure class 3. Whether such low SABP values resulted from an MVD-related decrease in cardiac output, an afterload reduction owing to cardiac treatment, or both, remains to be determined.

  11. Clinical outcome of stand-alone ALIF compared to posterior instrumentation for degenerative disc disease: A pilot study and a literature review.

    PubMed

    Udby, Peter M; Bech-Azeddine, Rachid

    2015-06-01

    The objective of the article was to: a) present results from a case cohort pilot study comparing stand-alone ALIF and TLIF and, b) review the literature on studies comparing the clinical outcome of stand-alone ALIF with posterior instrumentation including TLIF or PLIF, in patients with disabling low back pain resulting from degenerative disc disease. ALIF surgery has previously been linked with certain high risk complications and unfavorable long term fusion results. Newer studies suggest that stand-alone ALIF can possibly be advantageous compared to other types of posterior instrumented interbody fusion for a selected group of DDD patients. The methods and material consisted of a cohort pilot study of patients, with DDD treated with stand-alone ALIF or TLIF followed by a literature review conducted through a comprehensive PubMed database search of the English literature. Studies comparing stand-alone ALIF with posterior instrumented interbody fusion were selected and reviewed. Results from the pilot study, n = 21, showed a reduced perioperative blood loss, shorter operative time and a trend towards better pain reduction and decreased use of opioid analgesics in patients undergoing stand-alone ALIF compared to posterior instrumented fusion with TLIF. The literature review included three studies, n = 630. All three studies were retrospective cohort studies. The average patient follow-up was 2-years but with heterogeneous selected outcomes. Two of three articles documented significant advantages when using stand-alone ALIF on outcomes such as ODI, VAS, surgical time, blood loss and patient satisfaction. No study found stand-alone ALIF inferior in chosen outcomes including fusion. In conclusion the pilot study and the literature review, finds similar clinical outcomes and fusion rates after stand-alone ALIF and posterior interbody fusion. Stand-alone ALIF was associated with a shorter duration of surgery, less perioperative blood loss and a faster improvement post

  12. 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

  13. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation

    PubMed Central

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S.

    2016-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties. PMID:26793063

  14. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation.

    PubMed

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S

    2015-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

  15. Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation.

    PubMed

    Goo, Yong Sook; Park, Dae Jin; Ahn, Jung Ryul; Senok, Solomon S

    2015-01-01

    Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties. PMID:26793063

  16. 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.

  17. 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

  18. Ultra-high resolution adaptive optics: optical coherence tomography for in vivo imaging of healthy and diseased retinal structures

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Zhang, Yan; Jones, Steven M.; Choi, Stacey S.; Cense, Barry; Evans, Julia W.; Miller, Donald T.; Olivier, Scot S.; Werner, John S.

    2008-02-01

    Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.

  19. 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

  20. 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

  1. Photovoltaic retinal prosthesis: implant fabrication and performance

    PubMed Central

    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

    2012-01-01

    Objective To develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. Approach 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 (280μm, 140 μm, and 70 μm) with active electrodes of 80 μm, 40 μm and 20 μm in diameter were fabricated. Main results The turn-on voltages of one-, two- and three-series-connected photodiode structures are approximately 0.6V, 1.2V and 1.8V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ~0.36 A/W, 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. Significance 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. PMID:22791690

  2. 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

  3. 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

  4. Stereotypic behaviors in degenerative dementias.

    PubMed

    Prioni, S; Fetoni, V; Barocco, F; Redaelli, V; Falcone, C; Soliveri, P; Tagliavini, F; Scaglioni, A; Caffarra, P; Concari, L; Gardini, S; Girotti, F

    2012-11-01

    Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

  5. [Degenerative adult scoliosis].

    PubMed

    García-Ramos, C L; Obil-Chavarría, C A; Zárate-Kalfópulos, B; Rosales-Olivares, L M; Alpizar-Aguirre, A; Reyes-Sánchez, A A

    2015-01-01

    Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance. PMID:27012088

  6. [Degenerative adult scoliosis].

    PubMed

    García-Ramos, C L; Obil-Chavarría, C A; Zárate-Kalfópulos, B; Rosales-Olivares, L M; Alpizar-Aguirre, A; Reyes-Sánchez, A A

    2015-01-01

    Adult scoliosis is a complex three-dimensional rotational deformity of the spine, resulting from the progressive degeneration of the vertebral elements in middle age, in a previously straight spine; a Cobb angle greater than 10° in the coronal plane, which also alters the sagittal and axial planes. It originates an asymmetrical degenerative disc and facet joint, creating asymmetrical loads and subsequently deformity. The main symptom is axial, radicular pain and neurological deficit. Conservative treatment includes drugs and physical therapy. The epidural injections and facet for selectively blocking nerve roots improves short-term pain. Surgical treatment is reserved for patients with intractable pain, radiculopathy and/ or neurological deficits. There is no consensus for surgical indications, however, it must have a clear understanding of the symptoms and clinical signs. The goal of surgery is to decompress neural elements with restoration, modification of the three-dimensional shape deformity and stabilize the coronal and sagittal balance.

  7. 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

  8. Retinal detachment

    PubMed Central

    2010-01-01

    Introduction Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, cryotherapy, daunorubicin, fluorouracil plus low molecular weight heparin, laser photocoagulation, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy. PMID:21406128

  9. 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

  10. 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

  11. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration.

    PubMed

    Gómez-Vicente, Violeta; Lax, Pedro; 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.

  12. 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.

  13. 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

  14. Olfactory dysfunction in degenerative ataxias.

    PubMed

    Connelly, T; Farmer, J M; Lynch, D R; Doty, R L

    2003-10-01

    Several lines of evidence suggest that the cerebellum may play a role in higher-order olfactory processing. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT), a standardised test of olfactory function, to patients with ataxias primarily due to cerebellar pathology (spinocerebellar ataxias and related disorders) and to patients with Friedreich ataxia, an ataxia associated mainly with loss of afferent cerebellar pathways. UPSIT scores were slightly lower in both patient groups than in the control subjects, but no differences were noted between the scores of the Friedreich and the other ataxia patients. Within the Friedreich ataxia group, the smell test scores did not correlate with the number of pathologic GAA repeats (a marker of genetic severity), disease duration, or categorical ambulatory ability. UPSIT scores did not correlate with disease duration, although they correlated marginally with ambulatory status in the patients with cerebellar pathology. This study suggests that olfactory dysfunction may be a subtle clinical component of degenerative ataxias, in concordance with the hypothesis that the cerebellum or its afferents plays some role in central olfactory processing.

  15. Surgical removal of fragmented coronoid processes and fractured anconeal process in an older dog with evidence of severe degenerative joint disease.

    PubMed

    Flo, G L

    1998-12-15

    A 10-year-old Labrador Retriever was admitted because of severe unilateral (left) forelimb lameness of 6 weeks' duration. Computerized tomography revealed bilateral fragmented coronoid processes (FCP) and unilateral fracture of the anconeal process. Surgery on the left elbow to remove the loose anconeal process and FCP resolved the severe lameness and improved the dog's overall activity, compared with that of the preceding 2 years. Unstable FCP can develop late in life, and a degenerative anconeal process may fracture. Surgical removal of loose fragments in a severely arthritic joint may be beneficial. PMID:9861974

  16. Germ-line mutations in the neurofibromatosis 2 gene: Correlations with disease severity and retinal abnormalities

    SciTech Connect

    Parry, D.M.; Kaiser-Kupfer, M.; Eldridge, R.

    1996-09-01

    Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P {le} .05) for nearly every variable. Patients with nonsense or frameshift mutations were younger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study. 58 refs., 2 tabs.

  17. 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

  18. Degenerative mitral valve regurgitation: best practice revolution

    PubMed Central

    Adams, David H.; Rosenhek, Raphael; Falk, Volkmar

    2010-01-01

    Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation. PMID:20624767

  19. 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

  20. 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

  1. 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

  2. Genetic and degenerative disorders primarily causing other movement disorders.

    PubMed

    Pavese, Nicola; Tai, Yen F

    2016-01-01

    In this chapter, we will discuss the contributions of structural and functional imaging to the diagnosis and management of genetic and degenerative diseases that lead to the occurrence of movement disorders. We will mainly focus on Huntington's disease, Wilson's disease, dystonia, and neurodegeneration with brain iron accumulation, as they are the more commonly encountered clinical conditions within this group. PMID:27432681

  3. Retinal cartography.

    PubMed

    Mosier, M A

    1982-10-01

    This paper analyses retinal cartography in terms of its reflection of anatomic data and its relation to several forms of geographic methods of map-making. It shows that the distances between anatomic landmarks of the eye are reasonably similar to the relative distances on the retinal drawing chart currently used. Two forms of geographic cartography--azimuth equidistant and orthographic--are described and compared with retinal cartography. The retinal drawing chart currently used most closely approximates an azimuth equidistant projection, which suffers from circumferential distortion, a fact that retinal surgeons must keep in mind. It is therefore recommended that the chart be modified to have equally spaced concentric circles and clearer identification of the ora serrata; the present accurate marking of anatomic landmarks, such as the equator and the posterior border of the ciliary body, should be preserved.

  4. Attracting retinal cells to electrodes for high-resolution stimulation

    NASA Astrophysics Data System (ADS)

    Palanker, Daniel V.; Huie, Philip; Vankov, Alexander B.; Freyvert, Yev; Fishman, Harvey; Marmor, Michael F.; Blumenkranz, Mark S.

    2004-07-01

    Development of the electronic retinal prosthesis for restoration of sight in patients suffering from the degenerative retinal diseases faces many technological challenges. To achieve significant improvement in the low vision patients the visual acuity of 20/80 would be desirable, which corresponds to the pixel size of 20μm in the retinal implant. Stimulating current strongly (quadratically) depends on distance between electrode and cell. To achieve uniformity in stimulation thresholds, to avoid erosion of the electrodes and overheating of tissue, and to reduce the cross-talk between the neighboring pixels the neural cells should not be separated from electrodes by more than a few micrometers. Achieving such a close proximity along the whole surface of an implant is one of the major obstacles for the high resolution retinal implant. To ensure proximity of cells and electrodes we have developed a technique that prompts migration of retinal cells towards stimulating sites. The device consists of a multilayered membrane with an array of perforations of several (5-15) micrometers in diameter in which addressable electrodes can be embedded. In experiments in-vitro using explants of the whole retina of P7 rats, and in-vivo using adult rabbits and RCS rats the retinal tissue grew into the pores when membranes were positioned on the sub-retinal side. Histology has demonstrated that migrating cells preserve synaptic connections with cells outside the pores, thus allowing for signal transduction into the retina above the implant. Intimate proximity of cells to electrodes achieved with this technique allows for reduction of the stimulation current to 2μA at the 10μm electrode. A 3mm disk array with 18,000 pixels can stimulate cells with 0.5 ms pulses at 50Hz while maintaining temperature rise at the implant surface below 0.3°C. Such an implant can, in principle, provide spatial resolution geometrically corresponding to the visual acuity of 20/80 in a visual field of 10°.

  5. 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

  6. Animal models and different therapies for treatment of retinitis pigmentosa.

    PubMed

    Rivas, Miren Agurtzane; Vecino, Elena

    2009-10-01

    Retinitis pigmentosa (RP) is a heterogeneous group of retinal degenerative diseases initially affecting the rod photoreceptor. Patients present with night blindness, loss of peripheral vision and finally the loss of central vision, as a consequence of death of cone photoreceptors. RP is a genetic disease, showing inheritance of autosomal dominant (AD), autosomal recessive (AR) or X-linked (XL) recessive traits, although some patients have no family history of RP (simplex RP). Many animal models of RP are available and have led to a better understanding of the pathology of the disease, and to the development of therapeutic strategies aimed at curing or slowing down the genetic disorder. In this review, we describe the selected animal models (natural and transgenic) and their phenotypes and genotypes, as well as the advantages and disadvantages of the use of each animal. Also, we look at different therapeutic strategies being studied worldwide and report the latest results. Nevertheless, many obstacles will have to be overcome before most of these strategies can be applied to humans. PMID:19688697

  7. 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.

  8. 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.

  9. Disease Gene Candidates Revealed by Expression Profiling of Retinal Ganglion Cell Development

    PubMed Central

    Wang, Jack T.; Kunzevitzky, Noelia J.; Dugas, Jason C.; Cameron, Meghan; Barres, Ben A.; Goldberg, Jeffrey L.

    2010-01-01

    To what extent do postmitotic neurons regulate gene expression during development or after injury? We took advantage of our ability to highly purify retinal ganglion cells (RGCs) to profile their pattern of gene expression at 13 ages from embryonic day 17 through postnatal day 21. We found that a large proportion of RGC genes are regulated dramatically throughout their postmitotic development, although the genes regulated through development in vivo generally are not regulated similarly by RGCs allowed to age in vitro. Interestingly, we found that genes regulated by developing RGCs are not generally correlated with genes regulated in RGCs stimulated to regenerate their axons. We unexpectedly found three genes associated with glaucoma, optineurin, cochlin, and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), previously thought to be primarily expressed in the trabecular meshwork, which are highly expressed by RGCs and regulated through their development. We also identified several other RGC genes that are encoded by loci linked to glaucoma. The expression of glaucoma-linked genes by RGCs suggests that, at least in some cases, RGCs may be directly involved in glaucoma pathogenesis rather than indirectly involved in response to increased intraocular pressure. Consistent with this hypothesis, we found that CYP1B1 overexpression potentiates RGC survival. PMID:17687037

  10. Lens opacity induced by lipid peroxidation products as a model of cataract associated with retinal disease.

    PubMed

    Babizhayev, M A; Deyev, A I

    1989-07-17

    The cataractous lenses of patients with retinitis pigmentosa have been studied by electron microscopy. The posterior subcapsular opacities showed common ultrastructural features. Large areas of disruption of the lens fibre pattern were observed which showed an increase in the number of fibre membranes per unit area. In many regions an elaborate and regular folding of membranes was noted which produced complex 'figure-of-eight' and 'tramline' patterns, as well as membranous lamellar bodies. Masses of various size globules were also identified. It has been established that injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing lipid peroxidation products induces the development of posterior subcapsular cataract. Such modelling of cataract is based on a type of clouding of the crystalline lens similar to that observed in cataract resulting from diffusion of toxic lipid peroxidation products from the retina to the lens through the vitreous body on degeneration of the photoreceptors. Saturated liposomes (prepared from beta-oleoyl-gamma-palmitoyl-L-alpha-phosphatidylcholine) do not cause clouding of the lens, which demonstrates the peroxide mechanism of the genesis of this form of cataract. Clouding of the lens is accompanied by accumulation of fluorescing lipid peroxidation products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of reduced glutathione in the lens. From the results it is concluded that lipid peroxidation may initiate the development of cataract. PMID:2742866

  11. 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

  12. 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

  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. 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

  15. 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

  16. 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

  17. Retinal prosthetic strategy with the capacity to restore normal vision

    PubMed Central

    Nirenberg, Sheila; Pandarinath, Chethan

    2012-01-01

    Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20–25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their best hope is through prosthetic devices [reviewed in Chader et al. (2009) Prog Brain Res 175:317–332]. Current prosthetics, however, are still very limited in the vision that they provide: for example, they allow for perception of spots of light and high-contrast edges, but not natural images. Efforts to improve prosthetic capabilities have focused largely on increasing the resolution of the device’s stimulators (either electrodes or optogenetic transducers). Here, we show that a second factor is also critical: driving the stimulators with the retina’s neural code. Using the mouse as a model system, we generated a prosthetic system that incorporates the code. This dramatically increased the system’s capabilities—well beyond what can be achieved just by increasing resolution. Furthermore, the results show, using 9,800 optogenetically stimulated ganglion cell responses, that the combined effect of using the code and high-resolution stimulation is able to bring prosthetic capabilities into the realm of normal image representation. PMID:22891310

  18. Retinal prosthetic strategy with the capacity to restore normal vision.

    PubMed

    Nirenberg, Sheila; Pandarinath, Chethan

    2012-09-11

    Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20-25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their best hope is through prosthetic devices [reviewed in Chader et al. (2009) Prog Brain Res 175:317-332]. Current prosthetics, however, are still very limited in the vision that they provide: for example, they allow for perception of spots of light and high-contrast edges, but not natural images. Efforts to improve prosthetic capabilities have focused largely on increasing the resolution of the device's stimulators (either electrodes or optogenetic transducers). Here, we show that a second factor is also critical: driving the stimulators with the retina's neural code. Using the mouse as a model system, we generated a prosthetic system that incorporates the code. This dramatically increased the system's capabilities--well beyond what can be achieved just by increasing resolution. Furthermore, the results show, using 9,800 optogenetically stimulated ganglion cell responses, that the combined effect of using the code and high-resolution stimulation is able to bring prosthetic capabilities into the realm of normal image representation.

  19. [Progress of research in retinal image registration].

    PubMed

    Yu, Lun; Wei, Lifang; Pan, Lin

    2011-10-01

    The retinal image registration has important applications in the processes of auxiliary diagnosis and treatment for a variety of diseases. The retinal image registration can be used to measure the disease process and the therapeutic effect. A variety of retinal image registration techniques have been studied extensively in recent years. However, there are still many problems existing and there are numerous research possibilities. Based on extensive investigation of existing literatures, the present paper analyzes the feature of retinal image and current challenges of retinal image registration, and reviews the transformation models of the retinal image registration technology and the main research algorithms in current retinal image registration, and analyzes the advantages and disadvantages of various types of algorithms. Some research challenges and future developing trends are also discussed.

  20. 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.

  1. 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

  2. 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