Effects of Chymase on the Macular Region in Monkeys and Porcine Müller Cells: Probable Involvement of Chymase in the Onset of Idiopathic Macular Holes

Sugiyama, Tetsuya; Katsumura, Kozo; Nakamura, Kimitoshi; Kobayashi, Masato; Muramatsu, Michiko; Maruichi, Midori; Oku, Hidehiro; Miyazaki, Mizuo; Ikeda, Tsunehiko

doi:10.1159/000093072

Cited by 14 publications

(17 citation statements)

References 44 publications

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“…In a previous study, we performed immunostaining in cynomolgus monkey eyes for nestin, an NSC marker, in sections near the macula, mid-periphery, equator, and extreme periphery [10]. In that study, our comparison of nestin-positive cell density at each region clearly showed a higher density in the macula, but no significant differences among the other sites.…”

Section: Discussionmentioning

confidence: 82%

“…Since all retinal layers were excised in this present study, it is unclear which cells in the sensory retina expressed nestin. In our previous study that examined immunostaining for nestin in monkey eyes, many nestin-positive cells were observed in the inner nuclear layer and adjacent fovea [10]. This suggests that nestin may be expressed by Müller cells in the sensory retina or by Müller cell cones in the fovea.…”

Section: Discussionmentioning

confidence: 91%

“…In a previous study using tissue sections obtained from monkey eyes, we found strong positive staining in the fovea for the neural stem cell (NSC) marker nestin, and discussed its possible involvement in the onset of idiopathic macular holes [10]. In the present study, we also used monkey eyes to analyze the gene expression of the neural stem cell (NSC) markers nestin, PAX6, and SOX2 at different sites in the retina using real-time polymerase chain reaction (PCR).…”

Section: Introductionmentioning

confidence: 91%

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Expression Sites of Neural Stem Cell-Related Genes in the Monkey Retina

Shibata¹,

Ikeda²

2015

J Stem Cell Res Ther

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Objectives: Based on the hypothesis that undifferentiated retinal stem cell (RSC)-like cells exist in the fovea (the light-stressed, concave, avascular center of the retina where light is focused), we investigated the expression sites of neural stem cell (NSC)-related genes in the monkey retina.Methods: Cynomolgus monkeys were euthanized, and both eyes were then enucleated. Each eye was hemisected near the limbus, and flat-mounted retina samples were then prepared. Using a stereomicroscope, 1-mm x 1-mm blocks of the retina at the fovea, mid-periphery, and extreme periphery were then excised. These samples were used for real-time polymerase chain reaction analysis of the NSC-related gene (nestin, PAX6, and SOX2) expression at each site. Results:Nestin expression was high in the fovea, with a lower expression in the mid-periphery and extreme periphery. No differences in PAX6 gene expression were found in the fovea, mid-periphery, and extreme periphery. SOX2 expression was highest in the extreme periphery, with decreased expression in the mid-periphery and fovea. Conclusions:Our finding that nestin expression was highest in the fovea suggests that foveal retinal cells may have more undifferentiated characteristics that are different from retinal cells at other sites.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 91%

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Expression Sites of Neural Stem Cell-Related Genes in the Monkey Retina

Shibata¹,

Ikeda²

2015

J Stem Cell Res Ther

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“…16 This suggests that they originate from a metabolic dysfunction and supports the hypothesis of Müller cells implication in the pathogenesis of fullthickness MH. [17][18][19] In this study, we use en face OCT to characterize and quantify layer by layer, the perifoveal cystic cavities occurring around full-thickness MHs. To support the OCT findings, we used human and non-human primate macular flat-mounts and sections to visualize Müller cells stained with a glial marker.…”

mentioning

confidence: 99%

En Face Optical Coherence Tomography of Foveal Microstructure in Full-Thickness Macular Hole: A Model to Study Perifoveal Müller Cells

Matet¹,

Savastano²,

Rispoli³

et al. 2015

American Journal of Ophthalmology

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INTRODUCTIONEn-face optical coherence tomography (OCT) is an emerging imaging modality that facilitates the assessment of retinal structures transversely.1,2 Available since 2006 on certain OCT devices, the first retinal transverse scans were difficult to analyze interpret as only plane sections of the concave retina were available. 3 More recently, Spectral-Domain OCT technology with advanced alignment algorithm have adjusted sections to a reference curve, which has allowed layer-by-layer retinal imaging and provided a new investigation tool for a range of retinal disorders. 4-9The foveal microstructure is formed by a dense compaction of cone photoreceptors and their projected axons, which are intertwined with retinal glial Müller cells and follow a centrifugal course towards the inner layers at the edges of the fovea. Retinal glial Müller cells are critical for retinal homeostasis, providing metabolic support to neighboring neural cells, delivering neuroactive substances and retinoids to cones, and recycling waste compounds. 10,11 Müller cells are 5 times more abundant in the macula than in the peripheral retina.12 The "Z-shape" morphology of perifoveal Müller cells has been observed on histological sections in both animal and human models, where the cells adopt three consecutive orientations (Figure 1). 13,14 From the internal limiting membrane, perifoveal Müller cells run vertically to the inner nuclear layer, then turn inwards towards the foveal center across the outer plexiform layer and the Henle's fiber layer where their course is oblique and almost horizontal in the internal portion of the foveal pit. Then, at the junction with the outer nuclear layer, they take a vertical orientation again to reach the external limiting membrane (Figure 1). At the external limiting membrane of the primate retina, Omri et al. have previously shown that Müller cells and photoreceptors are bound by tight-like junctions, where the proteins occludin and zonula occludens-1 are expressed. 15Intraretinal fluid accumulation disrupts the foveal architecture, presenting an opportunity to examine its components in better detail. In full-thickness macular hole (MH), intraretinal cysts are frequently observed on OCT around the edges of the hole. On fluorescein angiography, no vascular leakage or filling of the cysts is usually observed. 16 This suggests that they originate from a metabolic dysfunction and supports the hypothesis of Müller cells implication in the pathogenesis of fullthickness MH. [17][18][19] In this study, we use en face OCT to characterize and quantify layer by layer, the perifoveal cystic cavities occurring around full-thickness MHs. To support the OCT findings, we used human and non-human primate macular flat-mounts and sections to visualize Müller cells stained with a glial marker. METHODS SubjectsThis observational case series adhered to the tenets of the Declaration of Helsinki, and the need of approval was waived by the Institutional Review Board of the Nuovo Regina Margherita Hospital, due to its retrospect...

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“…In addition, versican, through HA, reportedly binds to CD44, L-selectin, and P-selectin on cell membrane surfaces [30]. We previously reported the existence of more undifferentiated nestin-positive cells in the fovea than in other sites in the retina [31]. This suggests that in retinal ischemic diseases, such as diabetic retinopathy, HA-binding proteins such as CD44 and versican, which are not usually present in the fovea, increase with hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Expression of a hyaluronic acid-binding proteoglycan (versican) in the cynomolgus monkey eye

et al. 2016

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The expression of versican, a hyaluronic acid (HA)-binding protein, during the development and differentiation of the retina has been reported. In this study, we performed histochemical and immunohistological analysis of HA and versican from the ciliary body to the retina in cynomolgus monkey eyes. Paraffin-embedded sections of cynomolgus monkey eyes, including from the ciliary body to the macular region, were prepared. The distribution of versican and HA was examined by histochemical and immunohistochemical methods. The sites of HA expression and versican expression in the eye specimens were similar. Expression of HA and versican was observed in the peripheral retina and ciliary body, but not from the macular region to the mid-periphery of the retina. Versican was strongly expressed in the ciliary body, particularly in the non-pigmented ciliary epithelium. Expression in the retina from the periphery to posterior pole gradually decreased. Versican is expressed from the ciliary body to the peripheral retina, but this expression decreases toward the posterior pole. This suggests a physiological function for versican in the peripheral retina.

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Effects of Chymase on the Macular Region in Monkeys and Porcine Müller Cells: Probable Involvement of Chymase in the Onset of Idiopathic Macular Holes

Cited by 14 publications

References 44 publications

Expression Sites of Neural Stem Cell-Related Genes in the Monkey Retina

Expression Sites of Neural Stem Cell-Related Genes in the Monkey Retina

En Face Optical Coherence Tomography of Foveal Microstructure in Full-Thickness Macular Hole: A Model to Study Perifoveal Müller Cells

Expression of a hyaluronic acid-binding proteoglycan (versican) in the cynomolgus monkey eye

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