Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating antibodies specific to retinal proteins have been associated with retinal dysfunction in patients with retinopathy. Anti-recoverin antibodies found in patients with cancer-associated retinopathy (CAR) represent a unique model to study the relationship between retinal degeneration and autoimmunity. A body of evidence from in vitro and in vivo studies indicates that anti-recoverin autoantibodies are cytotoxic to retinal cells and induce apoptotic death of retinal photoreceptor cells, which leads to the degeneration of the photoreceptor cell layer. Similar to anti-recoverin autoantibodies, antibodies with other retinal specificities induce their target retinal cell death by activating a caspase 3-dependent apoptotic pathway. Thus, autoantibody-induced apoptosis may be a common pathway that leads to retinal death and blindness.
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PMID:Autoantibody-induced apoptosis as a possible mechanism of autoimmune retinopathy. 1284 60

A 60-year-old man was admitted for progressive visual loss in both eyes. He was diagnosed with retinopathy and chest computed tomography revealed an invasive thymoma. In western blot analysis, serum autoantibodies against recoverin, photoreceptor-specific calcium-binding protein, and heat shock cognate protein 70 which were identified as the cause of cancer-associated retinopathy (CAR). Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case.
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PMID:Invasive thymoma with paraneoplastic retinopathy. 1287 70

The goal of the present study was to analyze serum and tumor tissue of a patient with non-small cell lung cancer (NSCLC) for the presence of autoantibodies against recoverin (anti-Rc) and recoverin expression, correspondingly. Using immunoblotting with recombinant recoverin as an antigen, we have detected anti-Rc in serum of the patient. At the same time, the patient did not manifest any signs of cancer-associated retinopathy (CAR). Polyclonal (monospecific) antibodies against recoverin used for immunohistochemical analysis of the patient's tumor revealed recoverin expression in the tumor sections. To our knowledge, this is the first case of the presence of serum anti-Rc in NSCLC patients in the absence of paraneoplastic retina degeneration.
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PMID:Antirecoverin autoantibodies in the patient with non-small cell lung cancer but without cancer-associated retinopathy. 2759 42

Autoantibodies against recoverin are found in the sera of patients with cancer-associated retinopathy syndrome, a paraneoplastic disease associated with retinal degeneration. We have previously shown that anti-recoverin autoantibodies induced photoreceptor apoptotic cell death after injection into the vitreous of Lewis rats. Ciliary neurotrophic factor (CNTF) has been shown to promote the survival of a number of neuronal cell types, including photoreceptors. In this study, we examined whether an adeno-associated virus (AAV)-mediated delivery of gene encoding the human CNTF protected photoreceptor cells from anti-recoverin antibody-induced death. One month after subretinal injection of the AAV-CNTF gene into one eye and a control vector into the other eye, an anti-recoverin antibody was injected to induce retinal cell death in Lewis rats. Subretinal administration of the virus led to an efficient transduction of photoreceptors, as indicated by immunostaining of retinas with anti-CNTF. Histological examination of the corresponding retinas showed that photoreceptor cells were significantly protected from apoptotic death in the CNTF-treated eyes. CNTF treatment of the retinas resulted in a time-dependent activation of STAT 3. The present study shows that an AAV-mediated delivery of CNTF may protect photoreceptors from antibody-induced cell death through the activation of STAT3 and the suppression of caspase 3 activity, a key caspase leading to apoptosis. Thus, CNTF may be a useful treatment for human antibody-mediated retinal degeneration.
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PMID:Anti-apoptotic effects of CNTF gene transfer on photoreceptor degeneration in experimental antibody-induced retinopathy. 1293 81

Autoantibodies against alpha-enolase are often associated with visual loss in patients with autoimmune retinopathy. Anti-recoverin autoantibodies have been the most extensively studied for their pathologic association with cancer-associated retinopathy (CAR). It has been shown that anti-recoverin antibodies penetrate retinal layers corresponding to the cellular location of recoverin and cause the death of photoreceptors and bipolar cells. However, the pathogenic effects of anti-alpha-enolase antibodies have not been studied. In this study, we tested the labeling and apoptotic effects of such autoantibodies on retinal cells. Serum antibodies against alpha-enolase from patients with autoimmune retinopathy were tested ex vivo and in vivo in Sprague-Dawley rats. Autoantibodies to alpha-enolase specifically labeled the retinal ganglion cells and inner nuclear layer cells. Using ex vivo experiments and intravitreal injections, we observed that antibodies were capable of penetrating retinal tissue to target ganglion cell and inner nuclear layers and, consequently, were able to induce cell death through an apoptotic process. The apoptotic nuclei detected by a DNA fragmentation assay and caspase 3-positive cells were co-localized in the ganglion cell layer and inner nuclear layer. The results showed that antibodies against alpha-enolase target antigens in these layers and induce the apoptotic death of sensitive cells. Rat retinal explants and the intravitreal injection of antibodies provide us with a good model to identify antibody pathogenic targets in the retina. Such identification may help explain the complex of clinical symptoms for autoimmune retinopathy mediated by autoantibody and may help guide treatment strategies.
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PMID:Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy. 1532 34

We report the case of a patient who presented with cancer-associated retinopathy and small cell carcinoma of the lung, which was treated surgically because the initial diagnostic biopsy finding was squamous cell carcinoma. The patient then underwent chemotherapy and radiation therapy. We discuss the characteristics and pathogenesis of this paraneoplastic syndrome as well as its association with the lung tumor's aberrant production of a protein that competes with retinal recoverin at the photoreceptors of the retinal cone.
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PMID:[Small cell lung cancer and cancer-associated retinopathy]. 1571 5

Autoantibodies against recoverin, a Ca2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca2+. Intracellular Ca2+ was measured using the Ca2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca2+ channel blocker, significantly suppressed the increase of Ca2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca2+ is at least in part dependent on extracellular Ca2+. Nifedipine was found to inhibit the entry of Ca2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca2+ blockers in the treatment of the CAR syndrome.
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PMID:Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. 1642 15

In photoreceptor cells the Ca(2+) -binding protein recoverin controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1). It can also serve as a paraneoplastic antigen in the development of retinal degeneration in some patients with cancer. The aberrant expression of recoverin in cancer cells and the presence of autoantibodies against recoverin are essential for the occurrence of cancer-associated retinopathy, which finally results in the apoptosis of photoreceptor cells. Noteworthy in cancer patients, the aberrant recoverin expression and the appearance of autoantibodies against recoverin are more frequent than paraneoplastic syndromes. We suggest the term "cancer-retina antigens" for this kind of proteins like recoverin that are solely expressed in retina and tumor tissues and evoke antibodies and/or T cells in patients with cancer. The rare development of a paraneoplastic syndrome is possibly caused by this immune response and probably depends on further events allowing to overcome the blood-retina barrier and the immune privileged status of the retina. It is still unknown whether aberrantly expressed recoverin could have a specific function in cancer cells, though it is suggested that it can be functionally associated with G-protein-coupled receptor kinases. This paper reviews the present knowledge on paraneoplastic syndromes associated with the aberrant expression of recoverin. A possible application of recoverin as a potential target for immunotherapy of cancer is discussed.
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PMID:Recoverin as a cancer-retina antigen. 1644 17

Reports on cancer-associated retinopathies (CAR) have increased in recent years as the autoimmune reactions responsible have become better understood. The 23-kDalton autoantigen 'recoverin' was the first retinal antigen implicated in CAR, but others have since been described. We report an additional case involving an autoantigen other than recoverin, with five-year follow-up of a 50-year-old woman suffering from the CAR syndrome, with ocular abnormalities restricted to cone dysfunction. The patient had a history of laryngeal carcinoma surgically removed 18 months prior to presenting to the ophthalmologist with photophobia and decreased vision in both eyes. The patient's abnormal retinal hypersensitivity included antibody activity with two retinal antigens approximating 40 kD, located within the outer segments of the photoreceptor layer. To our knowledge, this is the first description of a cancer-associated, cone-specific dystrophy involving an abnormal amount of immunologic activity with two retinal proteins approximating 40 kD, that may prove to be isoforms of the same antigen.
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PMID:Cone dysfunction as a paraneoplastic syndrome associated with retinal antigens approximating 40 kiloDalton. 1675 7

We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.
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PMID:Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy. 1737 19


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