Macular Degeneration: Sato T

Wang J, Ohno-Matsui K, Yoshida T, Shimada N, Ichinose S, Sato T, Mochizuki M, Morita I. · Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan. · J Cell Physiol. · Pubmed #19277984 No free full text.

Abstract: One of the earliest signs of age-related macular degeneration (AMD) is the formation of drusen which are extracellular deposits beneath the retinal pigmented epithelium (RPE). To investigate the relationship between drusen and AMD, we focused on amyloid beta (Abeta), a major component of drusen and also of senile plaques in the brain of Alzheimer's patients. We previously reported that Abeta was accumulated in drusen-like structure in senescent neprilysin gene-disrupted mice. The purpose of this study was to investigate the influence of Abeta on factor B, the main activator of the complement alternative pathway. The results showed that Abeta did not directly modulate factor B expression in RPE cells, but increased the production of monocyte chemoattractant protein-1 (MCP-1). Abeta also increased the production of IL-1beta and TNF-alpha in macrophages/microglia, and exposure of RPE cells to IL-1beta and TNF-alpha significantly up-regulated factor B. Co-cultures of RPE cells and macrophages/microglia in the presence of Abeta significantly increased the expression of factor B in RPE. These findings indicate that cytokines produced by macrophages/microglia that were recruited by MCP-1 produced in RPE cells stimulated by Abeta up-regulate factor B in RPE cells. Thus, a combined mechanism exists for Abeta-induced for the activation of the complement alternative pathway in the subretinal space; cytokine-induced up-regulation of activator factor B and dysfunction of the inhibitor factor I by direct binding to Abeta as suggested in our earlier study.

Yoshida T, Ohno-Matsui K, Ichinose S, Sato T, Iwata N, Saido TC, Hisatomi T, Mochizuki M, Morita I. · Department of Ophthalmology and Visual Science and Instrumental Analysis Research Center, Tokyo Medical and Dental University, Tokyo, Japan. · J Clin Invest. · Pubmed #16167083 links to  free full text

Abstract: Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition Abeta. The results showed that Abeta treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Abeta-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Abeta reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.

Sato T, Iida T, Hagimura N, Kishi S. · Department of Ophthalmology, Gunma University School of Medicine, Maebashi, Gunma, Japan. · Retina. · Pubmed #15579989 No free full text.

Abstract: PURPOSE: To correlate optical coherence tomography (OCT) with angiographic signs of choroidal neovascularization (CNV) in retinal pigment epithelial detachment (PED) associated with age-related macular degeneration (ARMD). METHODS: Prospectively, the authors performed OCT in 35 eyes of 35 patients (30 men and 5 women with a mean age of 71.6 years [range, 56-76 years]) with ARMD. All 35 eyes had CNV in the area of PED or adjacent to it, which was shown by fluorescein or indocyanine green angiography. Cross-sectional images were obtained by the OCT scanning line through the CNV and PED. RESULTS: In 10 (56%) of 18 eyes in which the CNV was at the margin of the PED, a small PED was adjacent to the central, dome-shaped PED. There was a notch between the central and small mounds of PED. In 13 (76%) of 17 eyes in which the CNV was within the PED, a notch was seen in the dome-shaped PED, resulting in a contour with 2 mounds. One of the 2 mounds contained a highly reflective mass immediately beneath the detached retinal pigment epithelium in 8 (62%) of the 13 eyes. CONCLUSION: A tomographic notch in the PED may be diagnostically important as an indication of CNV beneath the detached retinal pigment epithelium in eyes with ARMD.

Sato T, Kanda T, Iida T, Takahashi T, Kishi S, Hoshino Y. · Department of Ophthalmology, Gunma University School of Medicine, Gunma, Japan. · J Int Med Res. · Pubmed #14587307 No free full text.

Abstract: We carried out an immunohistochemical investigation of the choroidal neovascular membranes from 12 eyes surgically excised as a result of age-related macular degeneration (n = 6) or idiopathic choroidal neovascularization (n = 6). Immunohistochemical staining was performed with antibodies specific for basic transcriptional element binding protein-2, actin or smooth muscle cell 1. In all membranes, the endothelial cells and stromal components around the vessels were immunoreactive for expression of basic transcriptional element binding protein-2, while immunoreactive expression of actin and smooth muscle cell type 1 was found in the surrounding stromal cells. These results suggest that basic transcriptional element binding protein-2, a zinc finger transcription factor, may contribute to the establishment of the choroidal neovascularization observed in the pathogenesis of age-related macular degeneration and idiopathic choroidal neovascularization.