Inherited Chorioretinal DystrophiesA Textbook and Atlas /

XV, 488 p. 428 illus., 339 illus. in color.onlin

Cancer-associated retinopathy (CAR) with electronegative ERG: a case report

Cancer-associated retinopathy (CAR) should be suspected in patients who present with visual symptoms such as rapid unexplained visual loss and seeing shimmering lights, with an abnormal ERG. Electronegative ERG responses are not exclusive to melanoma-associated retinopathy (MAR) but may be seen in CAR as well. We describe a patient with CAR who presented with an electronegative ERG. A 67-year old woman, who presented with complaints of seeing shimmering lights, underwent an extensive ophthalmological and electrophysiological examination. Best-corrected visual acuity was 7/10 in the right and 9/10 in the left eye. Goldmann visual fields showed relative central scotomata and concentric narrowing. Slit-lamp and fundus examination were normal as was fluorescein angiography. Rod-specific ERG responses were severely reduced, with electronegative maximal combined rod-cone responses and delayed cone-responses with normal amplitudes. Melanoma-associated retinopathy was suspected. Extensive dermatological and internal evaluation eventually revealed an oat-cell carcinoma in the right lung. The patient died of pneumonia 2 years after presentation

Invasion of retinal pigment epithelial cells: N-cadherin, hepatocyte growth factor, and focal adhesion kinase

PURPOSE. To investigate the role of N-cadherin and hepatocyte growth factor (HGF) in the invasion of collagen type I by human retinal pigment epithelial (RPE) cells. METHODS. RPE sheets from eight human eyes were used for characterization through Western blot analysis of the expression of cadherin in total lysates or after immunoprecipitation with anti �-catenin antibody. First-passage primary cultures of RPE sheets were successfully established from 28 of 56 human eyes. First-passage primary RPE cell cultures on glass substrate, consisting of patches of cells, were used for immunocytochemistry. Fifteen first-passage primary RPE cell cultures in culture vessels were grown to confluence. Four of the 15 first-passage primary RPE cell cultures were investigated for cadherin expression by immunocytochemistry, and the other 11 were further subcultured for two to six passages. These 11 culture

Structure and function of the N-cadherin/catenin complex in retinoblastoma

PURPOSE. To identify in human retinoblastoma and normal retinal tissue the type of cadherin, its relationship with cytoplasmic catenins, and its participation in invasion. METHODS. The cadherin/catenin complex was characterized in surgical retinoblastoma. specimens from five patients and human retinas from four donor eyes by immunocytochemistry, flow cytometry, and coimmunoprecipitation with antibodies against N-cadherin, alpha-catenin, and beta-catenin, followed by Western blot analysis or autoradiography. Y79 and WERI-Rb-1 retinoblastoma cell lines serve the evaluation of the cadherin/ catenin complex in aggregation and Collagen type I invasion in vitro. The association of the cadherin/catenin complex with the cytoskeleton was examined by an antibody-capping assay. RESULTS. In retinoblastoma and normal retina N-cadherin associated with a-catenin and beta-catenin but not E- or P-cadhcrin. The N-cadherin/catenin complex formed a regular, linear, and continuous honeycomb pattern in normal retina that was irregular, clustered, and interrupted in retinoblastoma. The Ncadherin/catenin complex was found also in the retinoblastoma cell lines WERI-Rb and Y79, in which it also showed an irregular pattern. Both cell lines were invasive in Collagen type I, and invasion was inhibited by the GC-4 antibody, which functionally neutralizes N-cadherin. Less GC-4 antibody was needed to inhibit invasion of Y79 cells, which expressed N-cadherin at a lower level, than to inhibit invasion of WERI-Rb-1 cells. In both cell lines, antibody capping of the N-cadherin/ catenin complex indicated that its linkage with the cytoskeleton were weak or absent. CONCLUSIONS. Retinoblastoma cells, in contrast with normal retina, express an N-cadherin/catenin complex that is irregularly distributed and weakly linked to the cytoskeleton. In retinoblastoma, this complex acts as an invasion promoter

Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)

PURPOSE: To investigate the genetic basis of autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare, inherited retinal dystrophy that may be associated with defects of ocular development, including nanophthalmos. METHODS: A combination of linkage analysis and DNA sequencing in five families was used to identify disease-causing mutations in VMD2. The effect of these mutations on splicing was assessed using a minigene system. RESULTS: Three pathogenic sequence alterations in VMD2 were identified in five families with nanophthalmos associated with ADVIRC. All sequences showed simultaneous missense substitutions and exon skipping. CONCLUSIONS: VMD2 encodes bestrophin, a transmembrane protein located at the basolateral membrane of the RPE, that is also mutated in Best macular dystrophy. We support that each heterozygous affected individual produces three bestrophin isoforms consisting of the wild type and two abnormal forms: one containing a missense substitution and the other an in-frame deletion. The data showed that VMD2 mutations caused defects of ocular patterning, supporting the hypothesized role for the RPE, and specifically VMD2, in the normal growth and development of the ey