Epistemic_Statements  

CORD-19:8c51cf0cc444f6a851ad178040369984759ddfec JSONTXT 8 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-64 Epistemic_statement denotes MINIREVIEWS Retinopathies Associated with Antiretinal Antibodies
T2 66-289 Epistemic_statement denotes The identification of autoantibodies during the course of a disease has been shown to be useful in making a diagnosis, understanding mechanisms of pathogenesis, identifying therapeutic strategies, and monitoring treatments.
T3 575-721 Epistemic_statement denotes The maintenance of self-tolerance within the retina may be overcome by a combination of factors, including both genetic and environmental factors.
T4 722-828 Epistemic_statement denotes In this review we highlight retinopathies that are associated with the presence of antiretinal antibodies.
T5 829-973 Epistemic_statement denotes We should stress that we are not inferring that all of the antiretinal antibodies described in this review are actually inducing ocular disease.
T6 974-1107 Epistemic_statement denotes Rather, we wish to highlight the concept that one may utilize sera to identify immune reactivity in the posterior segment of the eye.
T7 1108-1215 Epistemic_statement denotes The detection of autoantibodies may allow one to subtype the disease according to its autoantibody profile.
T8 1216-1321 Epistemic_statement denotes This process may help to define specific subgroups of retinopathies in terms of pathogenesis and therapy.
T9 1322-1496 Epistemic_statement denotes When there is immune-mediated retinal damage, it may result from a combination of factors, such as antibodies, activation of T cells and macrophages, and cytokine production.
T10 1497-1656 Epistemic_statement denotes In fact, cytokines, chemokines, and adhesion molecules produced by infiltrating and ocular resident cells may contribute significantly to ocular tissue damage.
T11 1657-1768 Epistemic_statement denotes A variety of human and experimental retinopathies are associated with the production of antiretinal antibodies.
T12 1769-2035 Epistemic_statement denotes As is shown in Table 1 , these retinopathies can be categorized into three groups: (i) visual paraneoplastic disorders, frequently referred to as cancer-associated retinopathies (CAR), (ii) infection-associated retinopathies and (iii) retinal degenerative disorders.
T13 2236-2320 Epistemic_statement denotes Melanoma-associated retinopathy (MAR) can occur in patients with cutaneous melanoma.
T14 2518-2649 Epistemic_statement denotes In these patients, antibodies develop with reactivity to the retina, and this response is associated with rod and cone dysfunction.
T15 2650-2739 Epistemic_statement denotes Visual loss occurs over months and may even precede the identification of the malignancy.
T16 2740-2849 Epistemic_statement denotes This association between progressive blindness as a remote effect of cancer was first reported in 1976 (48) .
T17 2850-3058 Epistemic_statement denotes Subsequent studies have shown that autoimmune mechanisms in cancer-induced blindness may be operative since patients with antiretinal, antiphotoreceptor cell antibodies responded to corticosteroids (22, 28) .
T18 3470-3571 Epistemic_statement denotes Analysis of retinal antigens has revealed that a variety of antigens may be involved in this process.
T19 4337-4431 Epistemic_statement denotes We should point out that spontaneous recovery of vision in this disease has not been reported.
T20 4701-4872 Epistemic_statement denotes It is generally believed that if immunosuppressive treatment is begun early in the course of the degenerative process, visual improvement or stabilization may be achieved.
T21 4873-5005 Epistemic_statement denotes However, therapy is not likely to be beneficial once widespread retinal degeneration has occurred (Keltner and Thirkill, Editorial).
T22 5106-5210 Epistemic_statement denotes This can be followed by a confirmatory assay such as Western blot and enzyme-linked immunosorbent assay.
T23 5211-5307 Epistemic_statement denotes Monitoring the level of antiretinal antibodies during immunosuppressive therapy has been tested.
T24 5523-5673 Epistemic_statement denotes Clearly, additional studies are needed to carefully evaluate fluctuations of the antibody titer during the course of the disease and during treatment.
T25 5674-5866 Epistemic_statement denotes Multicenter studies should be initiated to share sera and clinical information in order to determine if antibody profiles can be used as a marker to start, continue, and discontinue treatment.
T26 5867-5989 Epistemic_statement denotes The CAR syndrome is probably the most extensively studied blinding disease that is associated with antiretinal antibodies.
T27 6188-6320 Epistemic_statement denotes suggested that a mutational event inactivating the p53 tumor suppressor gene may turn on the synthesis of a recoverin protein (30) .
T28 6321-6425 Epistemic_statement denotes Antibodies reactive to recoverin may result in the blockage of ion channels and cellular depolarization.
T29 6426-6476 Epistemic_statement denotes These events may lead to photoreceptor cell death.
T30 6477-6613 Epistemic_statement denotes The possible mechanisms involved in anti-recoverin antibody-induced photoreceptor cell death have been examined in three recent reports.
T31 7011-7132 Epistemic_statement denotes These studies suggest that antibody-mediated degeneration of photoreceptors can occur through apoptotic mechanisms (60) .
T32 7228-7327 Epistemic_statement denotes Progressive visual loss develops over months and is frequently associated with metastatic melanoma.
T33 8425-8573 Epistemic_statement denotes Third, retinal cell damage can be induced by the self-reactive antibodies in vitro, and there is evidence of passive transfer of disease to animals.
T34 8574-8710 Epistemic_statement denotes The second group of retinopathies associated with antiretinal antibodies is retinal disorders that are triggered by an infectious agent.
T35 8848-8922 Epistemic_statement denotes Only a limited number of studies of retinal disorders have been performed.
T36 8923-9178 Epistemic_statement denotes We will highlight two human diseases triggered by Onchocerca volvulus or Toxoplasma gondii and an experimental model referred to as experimental coronavirus retinopathy (ECOR), triggered by the murine coronavirus, mouse hepatitis virus (MHV) ( Table 3) .
T37 9195-9315 Epistemic_statement denotes Infection with the nematode parasite O. volvulus can result in severe eye disease, often referred to as river blindness.
T38 9751-9866 Epistemic_statement denotes It is generally believed that ocular pathology is a result of host-directed inflammatory responses to the nematode.
T39 10025-10121 Epistemic_statement denotes A number of studies indicate that this retinal disease process may involve autoimmune responses.
T40 11205-11293 Epistemic_statement denotes This was also associated with extensive breakdown of the posterior blood-ocular barrier.
T41 11294-11458 Epistemic_statement denotes These studies indicate that molecular mimicry between O. volvulus and the human RPE protein may contribute to the retinopathy found in patients with onchocerciasis.
T42 11740-11831 Epistemic_statement denotes Historically, ocular manifestations were thought to be the result of congenital infections.
T43 11832-12012 Epistemic_statement denotes However, recent evidence accumulated over the past 10 years indicates that infection via ingestion of the parasite from contaminated soil or meat may also result in ocular disease.
T44 12013-12129 Epistemic_statement denotes In patients with toxoplasma retinochoroiditis, T. gondii cysts can be identified within the retina and the RPE cell.
T45 13024-13093 Epistemic_statement denotes We feel that this screening dilution is probably inappropriately low.
T46 13442-13596 Epistemic_statement denotes Taken together, these reports suggest a high prevalence of antiretinal antibodies directed against the photoreceptor layer in T. gondii-infected patients.
T47 13597-13689 Epistemic_statement denotes There is no evidence that these antibodies are acting alone to induce retinal tissue damage.
T48 13690-13840 Epistemic_statement denotes However, we do know from in vitro studies that T. gondii infections of human RPE cells result in the upregulation of a variety of cytokines (36, 37) .
T49 14007-14171 Epistemic_statement denotes As suggested by Rose, the cytokine profile initiated during the infection may drive the progression from benign autoimmunity to pathogenic autoimmune disease (47) .
T50 14628-14670 Epistemic_statement denotes However, infectious virus cannot be found.
T51 15210-15312 Epistemic_statement denotes Virus infections in man have frequently been associated with the development of autoimmune reactivity.
T52 15313-15454 Epistemic_statement denotes ECOR is an animal model system, which was established to delineate the possible mechanisms operative in virus-triggered retinal degeneration.
T53 15455-15626 Epistemic_statement denotes Thus, ECOR provides a model which suggests that some human retinal degenerative diseases with genetic predisposition and autoimmune components may be triggered by viruses.
T54 15689-15870 Epistemic_statement denotes However, our ability to determine which of these have a viral trigger and which do not has been hampered by difficulty obtaining ocular samples at the initial stages of the disease.
T55 15871-16068 Epistemic_statement denotes An alternative approach may consist of correlative studies to determine if certain retinal degenerative processes are associated with specific antiretinal antibodies that may have a viral etiology.
T56 16069-16204 Epistemic_statement denotes The third group of retinopathies associated with antiretinal antibodies is classified as the retinal degenerative disorders (Table 4) .
T57 16205-16478 Epistemic_statement denotes We have subdivided these disorders into five classes: retinitis pigmentosa (RP) with cystoid macular edema, recoverin-associated retinopathy (RAR), age-related macular degeneration, idiopathic retinopathies, and retinopathies associated with autoimmune neurologic diseases.
T58 16563-16647 Epistemic_statement denotes However, up to 60% of patients do not have a family history of retinal degeneration.
T59 16809-16903 Epistemic_statement denotes showed that these antiretinal antibodies can be directed against a neurofilament protein (15).
T60 16904-17058 Epistemic_statement denotes Moreover, RPE cells within the retinas of these patients have been upregulated to express major histocompatibility complex class I and II molecules (12) .
T61 17059-17259 Epistemic_statement denotes Patients with RP have been shown to have a breakdown in the retinal-blood barrier, and it has been difficult to associate the development of antiretinal antibodies with specific retinal tissue damage.
T62 17290-17442 Epistemic_statement denotes attempted to identify subpopulations of RP patients and to determine if antiretinal antibodies are associated with selected disease processes (19, 20) .
T63 17668-17783 Epistemic_statement denotes They found a significant association between cystoid macular edema and antiretinal antibodies in RP patients (20) .
T64 18655-18781 Epistemic_statement denotes Thus, clinical, electrophysiological, and immunological data were all present despite the absence of an underlying malignancy.
T65 18898-19050 Epistemic_statement denotes These studies indicate that recoverin-associated retinopathy in the absence of cancer may be a more widespread phenomena than was previously recognized.
T66 19057-19214 Epistemic_statement denotes Age-related macular degeneration (ARMD) is the most common cause of blindness in the United States and yet the etiology of this disease is still not defined.
T67 19587-19825 Epistemic_statement denotes The cross-reactivity of the serum antibodies with a protein of 58 to 62 kDa, the lower band present in a bovine purified neurofilament-68-kDa protein preparation, suggests that this protein may be a component of the neuronal cytoskeleton.
T68 19826-19961 Epistemic_statement denotes It is unclear whether these autoantibodies play a direct role in the etiology of ARMD or simply represent a response to retinal damage.
T69 19986-20123 Epistemic_statement denotes A variety of idiopathic retinopathies and retinal degenerative diseases have been associated with the presence of antiretinal antibodies.
T70 20587-20653 Epistemic_statement denotes Here, the presence of antibodies correlated with disease activity.
T71 20654-20754 Epistemic_statement denotes It is also possible that antiretinal antibodies play a role in the retinal white dot syndromes (9) .
T72 20837-21000 Epistemic_statement denotes In these diseases, it is not clear if the antibodies preceded the retinal disease or if the immune reactivity is a consequence of the retinal degenerative process.
T73 21001-21074 Epistemic_statement denotes In either case, the autoantibodies may contribute to the disease process.
T74 21075-21186 Epistemic_statement denotes Ideally, further study and characterization of autoreactivity may allow the subclassification of retinopathies.
T75 21187-21264 Epistemic_statement denotes This analysis may then be instrumental in the design of treatment strategies.
T76 21265-21340 Epistemic_statement denotes A number of retinal antigens have been evaluated and implicated in uveitis.
T77 21383-21497 Epistemic_statement denotes Both of these retinal antigens appear to play a role in T-cellmediated disease processes within the eye (39, 41) .
T78 21561-21679 Epistemic_statement denotes Finally, recent studies have identified that a neurological disease may also present with immune-mediated retinopathy.
T79 21792-21907 Epistemic_statement denotes Stiff-man syndrome is a rare neurological disorder which is characterized by rigid axial and proximal limb muscles.
T80 21908-22055 Epistemic_statement denotes An autoimmune pathogenesis is suggested due to the presence of autoantibodies directed against glutamic acid decarboxylase (GAD) in these patients.
T81 22185-22368 Epistemic_statement denotes The patient sera contained anti-GAD antibodies, which reacted with GABA-ergic retinal structures, suggesting that this reactivity may be associated with the ophthalmic manifestations.
T82 22491-22570 Epistemic_statement denotes However, these antibodies are directed against a variety of different antigens.
T83 22686-22835 Epistemic_statement denotes It is obvious that standardization of antiretinal reactivity is critical to both research studies and to the development of diagnostic assay systems.
T84 23125-23232 Epistemic_statement denotes The pathogenetic involvement of antibodies or cellular immunity to retinal proteins in humans is not clear.
T85 23233-23372 Epistemic_statement denotes In this brief review, we have presented evidence that selected retinopathies are associated with the development of antiretinal antibodies.
T86 23623-23824 Epistemic_statement denotes In infection-associated retinopathies, antibodies directed against an infectious agent may cross-react with retinal proteins or the antibodies react with retinal antigens released during the infection.
T87 23940-24179 Epistemic_statement denotes In these diseases it is difficult to determine if the antiretinal antibodies initiated the disease process or if the retinal degeneration occurred first and an immune response was later triggered against selected released retinal antigens.
T88 24180-24335 Epistemic_statement denotes Irrespective of the initiating event, the presence of antiretinal antibodies may contribute to the pathologic processes involved in selected retinopathies.
T89 24462-24597 Epistemic_statement denotes Nevertheless, demonstration of these antibodies may be helpful as diagnostic and prognostic markers in patients with reti-nal diseases.
T90 24598-24846 Epistemic_statement denotes Analysis of immune-mediated vision loss is in its infancy, and a careful analysis and characterization of antiretinal antibody specificies will help in our understanding of the mechanisms and the diagnosis of patients with this form of vision loss.