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Purpose: To determine whether vasohibin, an antiangiogenic factor produced by vascular endothelial cells, is expressed in the choroidal neovascular (CNV) membranes obtained from human eyes with age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). Design: Retrospective, interventional case series. Methods: The medical charts of 21 eyes of 21 patients with AMD or PCV who underwent surgical removal of the CNV membrane were reviewed. The removed tissues were immunostained for von Willebrand Factor (vWF), vascular endothelial growth factor (VEGF), and vasohibin. The levels of the messenger ribonucleic acid of VEGF, VEGFR2, and vasohibin were determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from the CNV membranes excised from nine AMD and nine PCV patients. Results: The patients were divided into three groups; four patients were placed in the most active group (Group H), 13 in the less active group (Group E), and four in the nonactive group (Group S). Immunohistochemistry showed that vasohibin, vWF, and VEGF were expressed in the vascular endothelial cells in the CNV membranes and in the polypoidal vessels. RT-PCR showed that there was a strong correlation between the level of expression of VEGFR2 and vasohibin (P = .0002). Eyes with a lower vasohibin-to-VEGF ratio tended to have larger subretinal hemorrhages or vitreous hemorrhages, whereas eyes with higher vasohibin-to-VEGF ratio had subretinal fibrosislike lesions. Statistical analysis of the vasohibin-to-VEGF ratio among the three groups was significant (P = .0209). Conclusions: Vasohibin is expressed in human CNV membranes. Our results indicate that the vasohibin-to-VEGF ratio may be related with the activity of the CNV. [Copyright &y& Elsevier]

Abstract: The transplantation of different types of cells into the eye to treat retinal diseases has advanced in the past 20 years. One of the types of cells used for transplantation is the iris pigment epithelial (IPE) cell, because autologous IPE cells are easily obtained and their properties are similar to those of retinal pigment epithelial (RPE) cells and retinal cells. IPE cells are transplanted as; freshly isolated or cultured cells to replace defective or diseased RPE cells, genetically modified IPE cells for delivering target molecules to the retina or RPE, and retinal progenitor cells. IPE cells have also been transplanted for non-retinal disorders. The survival of the transplanted cells in the host is an important factor for the success of transplantation. Autologous IPE cells have been found in the transplanted subretinal space and were able to phagocytose rod outer segments even 6 months after transplantation. Allogeneic and xenogenic cells will not remain in the region longer than autologous cells. Allogenic cells transplanted into the subretinal space are rejected in humans. Thus, we have transplanted cultured autologous IPE cells in 56 patients with age-related macular degeneration. The long-term results (more than 2 years with a maximum of 8 years) showed that the visual acuity (VA) was significantly improved over the pre-transplantation VA, although a slight decrease of VA was observed 2 weeks after the transplantation. One patient showed a vasculitis-like lesion. IPE cells that were transduced with neurotrophic factors by plasmid or viral vectors have also been transplanted in animals. We have transduced several neurotrophic factor genes into IPE cells with a plasmid vector, adeno-associated virus, or adenovirus. Transplantation of these transduced IPE cells into the subretinal space rescued photoreceptor cells from several types of photoreceptor toxicities. In addition, transduction of a gene into the IPE cells suppressed the systemic dissemination of the viral genome. The neuroprotective effects of the IPE cells were different for the different types of neurotrophic factor, and some of the neurotrophic factors may enhance systemic immune reaction after transplantation. IPE cells have also been used as retinal progenital cells because they originate from the same cell lines that give rise to the neural retina and RPE cells. The transduction of the photoreceptor-related homeobox gene was reported to induce photoreceptor phenotypes in IPE cells. Furthermore, transplantations of IPE cells have been performed to treat central nervous system disorders. In this review, we summarize recent progress on IPE transplantation. [Copyright &y& Elsevier]

Purpose: To determine whether hypothermia of 8°C can protect cultured human retinal pigment epithelial (ARPE-19) cells and rat retinal ganglion cells (RGC-5) against trypan blue (TB) toxicity. Design: Laboratory investigation. Methods: ARPE-19 cells and RGC-5 were exposed to balanced salt solution as controls, and 0.05% and 0.5% TB at 37°C, and at 8°C for one minute. The percentage of surviving cells was determined by the resazurin test. Results: TB induced a statistically significant decrease in the percentage of ARPE-19 cells surviving at 0.5% TB at 37°C (P < .01). Conversely, TB induced a statistically significant decrease in the percentage of RGC-5 surviving at all conditions except for 0.05% TB at 8°C (0.05% 37°C; P < .05, 0.5% 37°C and 8°C; P < .01). Conclusions: These results indicate that reducing the temperature to 8°C has a protective effect against the TB toxicity for ARPE-19 cells and RGC-5 in culture. [Copyright &y& Elsevier]

Purpose: To determine whether polymorphisms in the ARMS2 (LOC387715) gene and the lysyl oxidase–like 1 (LOXL1) gene are associated with age-related macular degeneration (AMD) in Japanese patients. Design: Clinically relevant laboratory investigation. Methods: Forty-one unrelated Japanese subjects with dry AMD, 50 subjects with exudative (wet) AMD, and 60 subjects with polypoidal choroidal vasculopathy (PCV) were studied. The single nucleotide polymorphisms (SNPs), p.Ala69Ser of the ARMS2 gene and p.Arg141Leu of the LOXL1 gene, were amplified by polymerase chain reaction, directly sequenced, and genotyped. Results: For the ARMS2 gene, the genotype frequency of the p.Ala69Ser single nucleotide polymorphism in eyes with dry AMD was not significantly different from that in the controls (P = .04), but the frequency was significantly higher in the exudative AMD group (P = 3.1 × 10−8) and PCV group (P = 6.9 × 10−3). For the LOXL1 gene, the genotype frequency of the p.Arg141Leu single nucleotide polymorphism was not statistically higher in the dry AMD and PCV groups than in the control group (dry AMD, P = .05; PCV, P = .16), but was statistically higher in the exudative AMD group (P = 6.8 × 10−3). Regression analyses showed significant associations between the ARMS2 gene and LOXL1 gene in patients with exudative AMD. Conclusions: The p.Ala69Ser polymorphism of the ARMS2 gene is strongly associated with exudative AMD and PCV and is associated marginally with dry AMD. The polymorphisms in the LOXL1 gene did not predispose the individual to dry AMD and PCV. These findings suggest that there is a significant association between the ARMS2 gene and LOXL1 gene in exudative AMD. [Copyright &y& Elsevier]