Autoantibodies to transducin in a patient with melanoma-associated retinopathy.

PURPOSE: To report novel immunoreactivity in a patient with melanoma-associated retinopathy. DESIGN: Retrospective case report and experimental study. METHODS: A 32-year-old woman with a history of metastatic melanoma presented with bilateral decreased visual acuity. Electroretinography, Goldmann perimetry, immunohistochemistry, and Western blotting of her serum were performed. RESULTS: Electroretinography showed a "negative" B-wave. Paracentral and central scotomas were observed on Goldmann perimetry. Antibodies to a retinal transducin were demonstrated by Western blotting. No immunoreactivity to retinal bipolar cells was detected by immunohistochemistry. CONCLUSION: Melanoma-associated retinopathy can be related to a variety of antiretinal antibodies. Recognition of transducin, a novel melanoma-associated retinopathy antigen, may be important for identifying and treating patients with night blindness and melanoma.

[Melanoma-associated retinopathy with night blindness. Case report]. / Melanom-assoziierte Retinopathie (MAR) mit Nachtblindheit. Fallbericht.

BACKGROUND: Night blindness is usually symptomatic of retinal dysfunction. However, apart from congenital forms of night blindness such as congenital stationary night blindness (CSNB) and pigmentary retinopathy without clumping of pigment, the acquired forms of night blindness present a particular diagnostic challenge to the ophthalmologist. CASE REPORT: A 51-year-old patient with formerly healthy eyes presented with malignant skin melanoma and sudden night blindness. Along with reduced acuity, concentric visual field limitation, and a marked decrease in sensitivity of the retinal rods and cones in adaptometrical tests, significantly reduced b waves and intact a waves were registered in the flash-ERG of both eyes with otherwise inconspicuous morphologic findings. Furthermore, serum levels of antibodies (IgG) against retinal bipolar cells were found to be increased. CONCLUSION: Results indicate the presence of melanoma-associated retinopathy (MAR), which-like carcinoma-associated retinopathy (CAR)-ranks among the tumor-associated diseases of the retina. CAR, MAR, and CSNB can be differentiated immunohistochemically by serum autoantibody determination and electrophysiologically by flash-ERG. As opposed to CAR, the immune response in the case of MAR is not to antigens of photoreceptors and ganglion cells, but to retinal so-called ON-depolarizing bipolar cells mainly connected in series to the rods. In addition, a waves are intact and b waves extinct, resembling the situation of CSNB.

Acquired unilateral night blindness associated with a negative electroretinogram waveform.

PURPOSE: The authors performed clinical, electrophysiologic, psychophysical, and immunologic studies in a patient who presented with an acquired night blindness in one eye to better define the clinical and functional changes in this rare disorder. METHODS: In addition to an ophthalmologic examination, the patient underwent the measurement of electroretinogram responses, dark-adapted thresholds using a Tübingen perimeter (Oculus, Tubingen, Germany), color vision assessment, kinetic visual-field testing using a Goldman perimeter, and immunologic testing to determine if the serum contained autoantibodies to retinal bipolar cells. RESULTS: Fundus examination showed no clinically apparent abnormality in either eye. The patient showed a selective reduction in the b-wave amplitude of the rod electroretinogram and an abnormality of the cone electroretinogram ON response in the affected left eye, whereas the rod and cone electroretinograms of the right eye were normal. Rod thresholds in the affected eye were elevated markedly, whereas rod thresholds in the right eye were normal centrally and slightly elevated in the far periphery. Immunologic testing did not show circulating autoantibodies to retinal cells. CONCLUSIONS: The patient examined in this study showed phenotypic similarities to patients with congenital stationary night blindness and to patients with an acquired form of night blindness associated with cutaneous melanoma (MAR syndrome). The electroretinogram findings from the patient are consistent with an acquired defect in signal transmission from photoreceptors to ON-type bipolar cells. However, the etiology of this unique form of unilateral night blindness remains obscure.

Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy.

PURPOSE: This study's goal was to determine the pathophysiology of the retinopathy that occurs in patients with metastatic cutaneous melanoma and sudden onset of night blindness, the so-called melanoma-associated retinopathy (MAR) syndrome. We tested the hypothesis that sera from two MAR patients contained autoantibodies that reacted with "on" bipolar cells of the human retina. METHODS: Immunofluorescence was performed on cryostat sections of unfixed normal human retinas. Sera and IgG fractions were tested from the two MAR patients and 38 control subjects (28 patients with metastatic melanoma, but no visual symptoms; two patients with non-MAR retinopathy; and eight normal subjects). RESULTS: The sera and IgG fractions from both MAR patients but from none of the control subjects produced heavy immunostaining of bipolar cells, which were identified as rod bipolars by a double labeling procedure using anti-protein kinase C. CONCLUSIONS: We hypothesize that MAR patients generate autoantibodies against a melanoma antigen that cross react with bipolar cells of the retina. These antibodies, by an unknown mechanism, may cause abnormalities of the rod and cone systems that are characteristic of MAR.

Role of autoimmunity in retinitis pigmentosa.

Twenty-five cases of retinitis pigmentosa were investigated to assess the cell-mediated immunity and for evidence of autoimmunity by measuring peripheral blood T-cell rosette count, cutaneous DTH response to recall antigens (Candida and purified protein derivative [PPD]), and 2:4 dinitrochlorobenzene (DNCB) and antiretinal antibody by tanned red cell hemagglutination technique. It was observed that cell-mediated immunity was significantly depressed, and antiretinal antibody was found in 60% of the cases, which correlated with the duration and severity of the disease. We conclude that although retinitis pigmentosa is genetically determined, patients develop autoimmunity against retinal tissue due to suppression of cell-mediated immunity. Association of rheumatoid factor in 8% of the cases further confirms the loss of homeostatic control owing to suppressed cell-mediated immunity.