Structure of the macroglia of the retina: Sharing and division of labour between astrocytes and Müller cells

Holländer, Horstmar; Makarov, F. N.; Dreher, Zofia; Driel, Diana van; Chan‐Ling, Tailoi; Stone, Jonathan

doi:10.1002/cne.903130405

Cited by 187 publications

(122 citation statements)

References 40 publications

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“…One is the differences in energy sources between the inner and outer retinas. The outer retina is fed by the choriocapillaries, of a fenestrated type, located in the innermost part of the choroids [5,22]. With these characteristics, the outer blood-retinal barrier requires the pigment epithelium to be tightly bound by tight junctions to protect the neural retina from the open circulation in the choroid.…”

Section: Discussionmentioning

confidence: 99%

“…This characteristic of the horizontal cells can make them sensitive to any minute alteration in the capillaries, which are the deepest and the finest in the retinal vasculature [4]. The degenerative processes in the IPL are found mainly near the radial processes of the Müller cells, which constitute one component of the inner bloodretinal barrier in the INL [22]. Degenerative profiles at the neuronal level occur time sequentially, in proportion to their distance from the vasculature.…”

Section: Discussionmentioning

confidence: 99%

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Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

et al. 2003

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Aims/hypothesis. Neurodegenerative changes in the diabetic retina occurring before diabetic retinopathy could be inevitable by the altered energy (glucose) metabolism, in the sense that dynamic image-processing activity of the retinal neurons is exclusively dependent on glucose. We therefore investigated the morphological changes in the neural retina, including neuronal cell death, of a streptozotocin-induced model of diabetes. Methods. Streptozotocin was intravenously injected. Rats were maintained hyperglycaemic without insulin treatment for 1 week and 4, 8, 12, and 24 weeks, respectively. Diabetic retinas were processed for histology, electron microscopy, and immunohistochemistry using the TUNEL method. Results. A slight reduction in the thickness of the inner retina was observed throughout the diabetic retinas and a remarkable reduction was seen in the outer nuclear layer 24 weeks after the onset of diabetes.The post-synaptic processes of horizontal cells in the deep invaginations of the photoreceptors showed degeneration changes from 1 week onwards. A few necrotic ganglion cells were observed after 4 weeks. At 12 weeks, some amacrine cells and a few horizontal cells showed necrotic features. Three to seven cellular layers in the outer nuclear layer and nerve terminals, rolled by the fine processes of the Müller cells near the somata of the degenerated ganglion cells, were apparent at 24 weeks. Apoptosis appeared in a few photoreceptor cells at 4 weeks, and the number of apoptotic photoreceptors increased thereafter. Conclusion/interpretation. These findings suggest that the visual loss associated with diabetic retinopathy could be attributed to an early phase of substantial photoreceptor loss, in addition to later microangiopathy. [Diabetologia (2003[Diabetologia ( ) 46:1260[Diabetologia ( -1268

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

et al. 2003

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“…Astrocytes and Müller cells are variants of retinal macroglia. Both contribute to the formation of the glia limitans of the retina (inner limiting membrane [ILM]), blood vessels, and the glial sheaths of neurons (Hollander et al 1991). Specific cytoplasmic expression of GFAP was detected in the NFL including the ILM, along the GCL, and around blood vessels in the neuroretina.…”

Section: Ihc Of Davidson's Fixed Paraffin-embedded Minipig Eyesmentioning

confidence: 99%

Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs

et al. 2015

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There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybridization (ISH) markers to porcine eyes. In this study, OCT and OCT angiography (AngioOCT) were performed on adult Gö ttingen minipigs. To increase structural information on retinal and choroidal vasculature, OCT data were speckle denoized and choroidal blood vessels were segmented with threshold filtering. In addition, we established a set of IHC and ISH markers on Davidson's fixed paraffin-embedded minipig eyes: neurofilament-160, neuronal nuclei, calretinin, protein kinase C-a, vimentin, glial fibrillary acidic protein, glutamine synthetase, ionized calcium-binding adaptor molecule-1, rhodopsin, synaptophysin, postsynaptic density protein-95, retinal pigment epithelium (RPE)-specific protein-65, von Willebrand factor, a-smooth muscle actin, desmin, and Ki-67, thus enabling visualization of retinal neuronal and glial cells, photoreceptors, synapses, RPE, blood vessels, myocytes, macrophages, or cell proliferation. Using ISH, transcripts of vascular endothelial growth factor A, angiopoietin-2, and endothelial tyrosine kinase were visualized. This article describes for the first time in minipig eyes speckle noise-free OCT, AngioOCT, and a set of IHC/ISH markers on Davidson's fixed paraffin-embedded tissues and helps to establish the minipig for ocular toxicology and pharmacology studies.

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“…The glial changes described to date relate to the pattern and level of expression of glial fibrillary acidic protein (GFAP). This intermediate filament protein is expressed in the normal retina mostly by astrocytes (the glia confined to the innermost region of the retina) and minimally by Mü ller cells (the glia that share functions with astrocytes in the inner retina but span the whole thickness of the retina with their radial processes) (3). In diabetes, Mü ller cells acquire prominent GFAP immunoreactivity throughout the extension of their processes (4,5), whereas astrocytes progressively lose GFAP immunoreactivity (6) and may also decrease in number (7); the levels of GFAP measured in the whole retina are increased (4,5).…”

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confidence: 99%

A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat

Asnaghi

Gerhardinger²,

Hoehn³

et al. 2003

Diabetes

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We tested the hypothesis that the apoptosis of inner retina neurons and increased expression of glial fibrillary acidic protein (GFAP) observed in the rat after a short duration of diabetes are mediated by polyol pathway activity. Rats with 10 weeks of streptozotocininduced diabetes and GHb levels of 16 ؎ 2% (mean ؎ SD) showed increased retinal levels of sorbitol and fructose, attenuation of GFAP immunostaining in astrocytes, appearance of prominent GFAP expression in Mü ller glial cells, and a fourfold increase in the number of apoptotic neurons when compared with nondiabetic rats. The cells undergoing apoptosis were immunoreactive for aldose reductase. Sorbinil, an inhibitor of aldose reductase, prevented all abnormalities. Intensive insulin treatment also prevented most abnormalities, despite reducing GHb only to 12 ؎ 1%. Diabetic mice, known to have much lower aldose reductase activity in other tissues when compared with rats, did not accumulate sorbitol and fructose in the retina and were protected from neuronal apoptosis and GFAP changes in the presence of GHb levels of 14 ؎ 2%. This work documents discrete cellular consequences of polyol pathway activity in the retina, and it suggests that activation of the pathway and "retinal neuropathy" require severe hyperglycemia and/or high activity of aldose reductase. These findings have implications for how to evaluate the role of the polyol pathway in diabetic retinopathy.

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Structure of the macroglia of the retina: Sharing and division of labour between astrocytes and Müller cells

Cited by 187 publications

References 40 publications

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs

A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat

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