Recurrent choroidal neovascularization after macular translocation surgery with 360-degree peripheral retinectomy.

PURPOSE: To evaluate the pattern of age-related macular degeneration in the new foveal location after macular translocation surgery with 360 degree peripheral retinectomy for neovascular age-related macular degeneration. METHODS: Clinical data, fundus photos, and fluorescein angiograms of patients in the Duke Macular Translocation Study were reviewed with 2-year follow-up data. RESULTS: With 56 patients completing follow-up, no patient developed de novo choroidal neovascularization (CNV), geographic atrophy, or drusen in the new subfoveal retinal pigment epithelium bed. By 2 years, 14 patients (25%) developed recurrent CNV and 13 of these 14 recurrences clearly arose from the old CNV bed. Of the 13 recurrences clearly arising from the old bed, 12 of them had recurrent CNV that involved the margin of the bed closest to the repositioned fovea. Smokers were 5.3 times (95% confidence interval: 1.2-24) more likely to develop recurrent CNV over 2 years. Despite treatment, median visual acuity for the 14 eyes with recurrent CNV was 20/200 compared with 20/80 in eyes without recurrence. CONCLUSIONS: Findings in this study support the hypotheses that the development of CNV occurs via a signaling mechanism from the fovea.

Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle - structure/function study of Xenopus IRBP.

BACKGROUND: Interphotoreceptor retinoid-binding protein's (IRBP) remarkable module structure may be critical to its role in mediating the transport of all-trans and 11-cis retinol, and 11-cis retinal between rods, cones, RPE and Müller cells during the visual cycle. We isolated cDNAs for Xenopus IRBP, and expressed and purified its individual modules, module combinations, and the full-length polypeptide. Binding of all-trans retinol, 11-cis retinal and 9-(9-anthroyloxy) stearic acid were characterized by fluorescence spectroscopy monitoring ligand-fluorescence enhancement, quenching of endogenous protein fluorescence, and energy transfer. Finally, the X-ray crystal structure of module-2 was used to predict the location of the ligand-binding sites, and compare their structures among modules using homology modeling. RESULTS: The full-length Xenopus IRBP cDNA codes for a polypeptide of 1,197 amino acid residues beginning with a signal peptide followed by four homologous modules each approximately 300 amino acid residues in length. Modules 1 and 3 are more closely related to each other than either is to modules 2 and 4. Modules 1 and 4 are most similar to the N- and C-terminal modules of the two module IRBP of teleosts. Our data are consistent with the model that vertebrate IRBPs arose through two genetic duplication events, but that the middle two modules were lost during the evolution of the ray finned fish. The sequence of the expressed full-length IRBP was confirmed by liquid chromatography-tandem mass spectrometry. The recombinant full-length Xenopus IRBP bound all-trans retinol and 11-cis retinaldehyde at 3 to 4 sites with Kd's of 0.2 to 0.3 microM, and was active in protecting all-trans retinol from degradation. Module 2 showed selectivity for all-trans retinol over 11-cis retinaldehyde. The binding data are correlated to the results of docking of all-trans-retinol to the crystal structure of Xenopus module 2 suggesting two ligand-binding sites. However, homology modeling of modules 1, 3 and 4 indicate that both sites may not be available for binding of ligands in all four modules. CONCLUSION: Although its four modules are homologous and each capable of supporting ligand-binding activity, structural differences between their ligand-binding domains, and interactions between the modules themselves will be critical to understanding IRBP's complex role in the visual cycle.