Müller cells and diabetic retinopathy

Coughlin, Brandon; Feenstra, Derrick; Mohr, Susanne

doi:10.1016/j.visres.2017.03.013

Cited by 253 publications

(210 citation statements)

References 116 publications

Supporting

Mentioning

200

Contrasting

Unclassified

Order By: Relevance

“…Diabetes-induced retinal vascular damages have been extensively studied by several laboratories [75][76][77]. Activation of the Muller glia is shown to be closely related to neurovascular changes in the diabetic retina [59,[78][79][80]. However, since the focus of our present study is solely on diabetes-induced neurodegeneration in the retina, we have not evaluated these changes in response to SMOX inhibition.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

View full text Add to dashboard Cite

Purpose Deregulation of polyamine metabolism has been implicated in various neurodegenerative disease and injury conditions. Studies from our laboratory have demonstrated that polyamine oxidation is a critical mediator of both neuronal and vascular injury in a mouse model of retinopathy of prematurity (Narayanan et al 2014; Patel et al 2016). The current study was undertaken to investigate the role of the polyamine oxidase spermine oxidase (SMO) in mediating neuronal damage and dysfunction in the diabetic retina. Methods Mice (8 weeks old, C57BL6J) were made diabetic by injection of streptozotocin (STZ, 65 mg/kg, pH 4.5, i.p.) and compared to age‐matched controls after 4 to 15 weeks of diabetes. Following the onset of hyperglycemia, mice were treated with either vehicle (normal saline) or SMO inhibitor, MDL 72527 (20 mg/kg of body weight, in saline, intra‐peritoneal, 3 times/week). Retinal neuronal function in living mice was determined by electroretinography (ERG). Retinal structure in the same mice was analyzed by Spectral Domain‐Optical Coherence Tomography (SD‐OCT). Following ERG and SD‐OCT analyses, mice were humanely euthanized, and retinas were collected and processed for immunofluorescence and western blot analyses. Results Western blot analysis showed that expression of SMO was increased in the diabetic retinas compared to controls. Inner retinal function studied by dark‐adapted electroretinography showed that the positive (pSTR) and negative (nSTR) scotopic threshold responses (measured at 110 ms and 200 ms), were significantly reduced (p<0.01, N=5–12) in the diabetic (4–12 weeks) mice as compared with the controls. The pSTR, but not the nSTR amplitudes were greatly improved in the MDL‐treated diabetic mice (p<0.05, N=5–10). The amplitude at 110 ms was dominated by the b‐wave at higher intensities and was significantly stronger in the MDL72527‐treated mice than in the vehicle‐treated diabetic mice. SD‐OCT analysis demonstrated a significant thinning of retina in the diabetic mice (p<0.01, N=5–12), which was improved in the MDL‐treated group. These data demonstrate a partial rescue of inner retinal function and retinal structure by SMO inhibition in the diabetic retina. Studies on the impact of MDL72527 treatment on neuronal survival are currently in progress. Conclusion Our results show the specific involvement of Spermine Oxidase in mediating neuronal injury in the diabetic retina and demonstrate its potential as a therapeutic target for mitigating neuronal injury in diabetic retinopathy. Support or Funding Information These studies supported by the National Eye Institute (1R01EY028569 to S.P.N) and Augusta University Culver Vision Discovery institute pilot grant to S.P.N. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…Although MGCs are highly resistant cells, they can activate the caspase‐1 pathway, leading to pyroptosis, an infrequent cell death program. The Mohr group suggested that pyroptosis could be a mechanism to eliminate MGCs secreting IL‐1β, in order to decrease retinal inflammation (Coughlin, Feenstra, & Mohr, ).…”

Section: Diabetic Retinopathymentioning

confidence: 99%

A journey into the retina: Müller glia commanding survival and death

Subirada

Paz

Ridano

et al. 2018

Eur J of Neuroscience

View full text Add to dashboard Cite

Müller glial cells (MGCs) are known to participate actively in retinal development and to contribute to homoeostasis through many intracellular mechanisms. As there are no homologous cells in other neuronal tissues, it is certain that retinal health depends on MGCs. These macroglial cells are located at the centre of the columnar subunit and have a great ability to interact with neurons, astrocytes, microglia and endothelial cells in order to modulate different events. Several investigations have focused their attention on the role of MGCs in diabetic retinopathy, a progressive pathology where several insults coexist. As expected, data suggest that MGCs display different responses according to the severity of the stimulus, and therefore trigger distinct events throughout the course of the disease. Here, we describe physiological functions of MGCs and their participation in inflammation, gliosis, synthesis and secretion of trophic and antioxidant factors in the diabetic retina. We invite the reader to consider the protective/deleterious role of MGCs in the early and late stages of the disease. In the light of the results, we open up the discussion around and ask the question: Is it possible that the modulation of a single cell type could improve or even re-establish retinal function after an injury?

show abstract

“…Recent studies, however, have demonstrated that retinal neurodegeneration is a critical feature associated with the progression of the disease and that early retinal neuronal injury actually precedes microangiopathy (18)(19)(20)(21)(22)(23). Indeed, all retinal layers (ganglion, bipolar, amacrine, and photoreceptor cell), demonstrate altered functions (as assessed by electroretinography and central vision analysis under reduced contrast and luminance conditions) prior to observable micropathy lesions (as assessed by fundus photography) (24)(25)(26)(27)(28)(29). Therefore, defining diabetic retinopathy simply as a "microvascular complication of diabetes" is a misnomer and restricts our understanding of the condition as well as potential therapeutic approaches to address it.…”

Section: Introductionmentioning

confidence: 99%

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Sinclair

Schwartz

2019

Front. Endocrinol.

View full text Add to dashboard Cite

Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

show abstract

Müller cells and diabetic retinopathy

Cited by 253 publications

References 116 publications

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

A journey into the retina: Müller glia commanding survival and death

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Contact Info

Product

Resources

About