Ultrastructural lesions of retinal pericapillary Müller cells in streptozotocin-induced diabetic rats

Hori, Shingo; Mukai, Noritsugu

doi:10.1007/bf02391205

Cited by 30 publications

(18 citation statements)

References 13 publications

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“…Based on these results and considering that the phagocytic character of Müller cells manifested only in the NFL, it is highly likely that the debris from the delayed degeneration of nerve fibers is cleared by activated Müller end feet. This proposition remains equivocal, even though in vitro studies have reported a phagocytic function for Müller cells [38,39], and ultrastructural studies an increased lysosomal content in the Müller cells of streptozotocin-induced diabetic rats [40,41].…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2003

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“…Several other studies are in line with our observation that Müller cells die in a hyperglycemic environment. The first study to describe dying Müller cells in diabetic retinopathy was done using EM analysis[126]. Dying Müller cells are described as being hypertrophic consistent with the notion that during pyroptosis, cells swell rather than shrink as observed in apoptotic cell death[48].…”

Section: Müller Cell Loss In Diabetic Retinopathymentioning

confidence: 93%

“…On the bad side – Müller cell death will promote loss of retinal blood barrier integrity, increased vascular permeability, and loss of neuroprotection affecting both neurons and vascular cells. Loss of Müller cells in diabetes has also been associated with aneurysm formation, a clinical characteristic of diabetic retinopathy[126]. However, one can also argue that on the good side – removal of activated and pro-inflammatory Müller cells might be a “shut off” mechanism to deal with an increasing inflammatory environment in the diabetic retina.…”

Section: Müller Cell Loss In Diabetic Retinopathymentioning

confidence: 99%

Müller cells and diabetic retinopathy

2017

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Müller cells are one of the primary glial cell types found in the retina and play a significant role in maintaining retinal function and health. Since Müller cells are the only cell type to span the entire width of the retina and have contact to almost every cell type in the retina they are uniquely positioned to perform a wide variety of functions necessary to maintaining retinal homeostasis. In the healthy retina, Müller cells recycle neurotransmitters, prevent glutamate toxicity, redistribute ions by spatial buffering, participate in the retinoid cycle, and regulate nutrient supplies by multiple mechanisms. Any disturbance to the retinal environment is going to influence proper Müller cell function and well being which in turn will affect the entire retina. This is evident in a disease like diabetic retinopathy where Müller cells contribute to neuronal dysfunction, the production of pro-angiogenic factors leading to neovascularization, the set up of a chronic inflammatory retinal environment, and eventual cell death. In this review, we highlight the importance of Müller cells in maintaining a healthy and functioning retina and discuss various pathological events of diabetic retinopathy in which Müller cells seem to play a crucial role. The beneficial and detrimental effects of cytokine and growth factor production by Müller cells on the microvasculature and retinal neuronal tissue will be outlined. Understanding Müller cell functions within the retina and restoring such function in diabetic retinopathy should become a cornerstone for developing effective therapies to treat diabetic retinopathy.

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“…Previous studies have shown that after 7 months of diabetes, Müller cells are lost in the retinas of diabetic mice 16 and that Müller cell loss is associated with programmed cell death. 17–19 In vitro studies have shown that HG promotes Müller cell apoptosis by decreasing Akt activity. 20 Taken together, these studies provide evidence for Müller cell loss in the diabetic retina.…”

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confidence: 99%

High Glucose Induces Mitochondrial Dysfunction in Retinal Müller Cells: Implications for Diabetic Retinopathy

Tien

Zhang

Muto

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeTo investigate whether high glucose (HG) induces mitochondrial dysfunction and promotes apoptosis in retinal Müller cells.MethodsRat retinal Müller cells (rMC-1) grown in normal (N) or HG (30 mM glucose) medium for 7 days were subjected to MitoTracker Red staining to identify the mitochondrial network. Digital images of mitochondria were captured in live cells under confocal microscopy and analyzed for mitochondrial morphology changes based on form factor (FF) and aspect ratio (AR) values. Mitochondrial metabolic function was assessed by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a bioenergetic analyzer. Cells undergoing apoptosis were identified by differential dye staining and TUNEL assay, and cytochrome c levels were assessed by Western blot analysis.ResultsCells grown in HG exhibited significantly increased mitochondrial fragmentation compared to those grown in N medium (FF = 1.7 ± 0.1 vs. 2.3 ± 0.1; AR = 2.1 ± 0.1 vs. 2.5 ± 0.2; P < 0.01). OCR and ECAR were significantly reduced in cells grown in HG medium compared to those grown in N medium (steady state: 75% ± 20% of control, P < 0.02; 64% ± 22% of control, P < 0.02, respectively). These cells also exhibited a significant increase (∼2-fold) in the number of apoptotic cells compared to those grown in N medium (P < 0.01), with a concomitant increase in cytochrome c levels (247% ± 94% of control, P < 0.05).ConclusionsFindings indicate that HG-induced mitochondrial morphology changes and subsequent mitochondrial dysfunction may contribute to retinal Müller cell loss associated with diabetic retinopathy.

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Ultrastructural lesions of retinal pericapillary Müller cells in streptozotocin-induced diabetic rats

Cited by 30 publications

References 13 publications

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

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

Müller cells and diabetic retinopathy

High Glucose Induces Mitochondrial Dysfunction in Retinal Müller Cells: Implications for Diabetic Retinopathy

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