scholarly journals The Absence of Indoleamine 2,3-Dioxygenase Inhibits Retinal Capillary Degeneration in Diabetic Mice

2018 ◽  
Vol 59 (5) ◽  
pp. 2042 ◽  
Author(s):  
Rooban B. Nahomi ◽  
Sruthi Sampathkumar ◽  
Angela M. Myers ◽  
Lynda Elghazi ◽  
Dawn G. Smith ◽  
...  
Keyword(s):  
Diabetic Mice ◽  
Indoleamine 2,3 Dioxygenase ◽  
Retinal Capillary ◽  
Capillary Degeneration

scholarly journals Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer’s disease

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Haoshen Shi ◽  
Yosef Koronyo ◽  
Dieu-Trang Fuchs ◽  
Julia Sheyn ◽  
Kolja Wawrowsky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tight Junction ◽  
Immunofluorescent Staining ◽  
Vascular Changes ◽  
Wild Type ◽  
Blood Retinal Barrier ◽  
Retinal Capillary ◽  
Capillary Degeneration ◽  
Pericyte Loss

AbstractExtensive effort has been made studying retinal pathology in Alzheimer’s disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal vascular changes and their possible relationships with vascular amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, vascular amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P < 0.0001). This small vessel degeneration reached significance in 8-month-old mice (P = 0.0035), with males more susceptible than females. Degeneration of retinal capillaries also progressively increased with age in healthy mice (P = 0.0145); however, the phenomenon was significantly worse during AD-like progression (P = 0.0001). A substantial vascular PDGFRβ deficiency (~ 50% reduction, P = 0.0017) along with prominent vascular Aβ deposition was further detected in the retina of ADtg mice, which inversely correlated with the extent of degenerated capillaries (Pearson’s r = − 0.8, P = 0.0016). Importantly, tight-junction alterations such as claudin-1 downregulation and increased BRB permeability, demonstrated in vivo by retinal fluorescein imaging and ex vivo following injection of FITC-dextran (2000 kD) and Texas Red-dextran (3 kD), were found in ADtg mice. Overall, the identification of age- and Alzheimer’s-dependent retinal capillary degeneration and compromised BRB integrity starting at early disease stages in ADtg mice could contribute to the development of novel targets for AD diagnosis and therapy.

scholarly journals Deletion of Aldose Reductase from Mice Inhibits Diabetes-Induced Retinal Capillary Degeneration and Superoxide Generation

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62081 ◽  
Author(s):  
Jie Tang ◽  
Yunpeng Du ◽  
J. Mark Petrash ◽  
Nader Sheibani ◽  
Timothy S. Kern
Keyword(s):  
Aldose Reductase ◽  
Superoxide Generation ◽  
Retinal Capillary ◽  
Capillary Degeneration

Immunoprotection and Functional Improvement of Allogeneic Islets in Diabetic Mice, Using a Stable Indoleamine 2,3-Dioxygenase Producing Scaffold

2015 ◽  
Vol 99 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
Azadeh Hosseini-Tabatabaei ◽  
Reza Baradar Jalili ◽  
Mohsen Khosravi-Maharlooei ◽  
Ryan Hartwell ◽  
Ruhangiz T. Kilani ◽  
...  
Keyword(s):  
Functional Improvement ◽  
Diabetic Mice ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals RORγt Inhibitor-SR1001 Halts Retinal Inflammation, Capillary Degeneration, and the Progression of Diabetic Retinopathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3547
Author(s):  
Thomas E. Zapadka ◽  
Sarah I. Lindstrom ◽  
Brooklyn E. Taylor ◽  
Chieh A. Lee ◽  
Jie Tang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Microvascular Disease ◽  
Orphan Receptor ◽  
Vascular Pathology ◽  
Diabetic Mice ◽  
Molecule Inhibitor ◽  
Working Age ◽  
Endothelial Cell Death ◽  
Retinal Inflammation ◽  
Capillary Degeneration

Diabetic retinopathy is a diabetes-mediated retinal microvascular disease that is the leading cause of blindness in the working-age population worldwide. Interleukin (IL)-17A is an inflammatory cytokine that has been previously shown to play a pivotal role in the promotion and progression of diabetic retinopathy. Retinoic acid-related orphan receptor gammaT (RORγt) is a ligand-dependent transcription factor that mediates IL-17A production. However, the role of RORγt in diabetes-mediated retinal inflammation and capillary degeneration, as well as its potential therapeutic attributes for diabetic retinopathy has not yet been determined. In the current study, we examined retinal inflammation and vascular pathology in streptozotocin-induced diabetic mice. We found RORγt expressing cells in the retinal vasculature of diabetic mice. Further, diabetes-mediated retinal inflammation, oxidative stress, and retinal endothelial cell death were all significantly lower in RORγt−/− mice. Finally, when a RORγt small molecule inhibitor (SR1001) was subcutaneously injected into diabetic mice, retinal inflammation and capillary degeneration were ameliorated. These findings establish a pathologic role for RORγt in the onset of diabetic retinopathy and identify a potentially novel therapeutic for this blinding disease.

scholarly journals Connective Tissue Growth Factor Is Necessary for Retinal Capillary Basal Lamina Thickening in Diabetic Mice

2008 ◽  
Vol 56 (8) ◽  
pp. 785-792 ◽  
Author(s):  
Esther J. Kuiper ◽  
Rogier van Zijderveld ◽  
Peggy Roestenberg ◽  
Karen M. Lyons ◽  
Roel Goldschmeding ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Basal Lamina ◽  
Tissue Growth ◽  
Diabetic Mice ◽  
Retinal Capillary

Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus

2007 ◽  
Vol 23 (2) ◽  
pp. 152-156 ◽  
Author(s):  
Rachel Miller-Lotan ◽  
Benjamin Miller ◽  
Farid Nakhoul ◽  
Doron Aronson ◽  
Roy Asaf ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Genetically Modified ◽  
Membrane Thickness ◽  
Diabetic Mice ◽  
Basement Membrane Thickness ◽  
Capillary Basement Membrane ◽  
Retinal Capillary

scholarly journals Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability

2015 ◽  
Vol 29 (5) ◽  
pp. 2194-2204 ◽  
Author(s):  
Yunpeng Du ◽  
Megan Cramer ◽  
Chieh Allen Lee ◽  
Jie Tang ◽  
Arivalagan Muthusamy ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Diabetic Mice ◽  
Superoxide Generation ◽  
Capillary Degeneration

scholarly journals Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes

2013 ◽  
Vol 93 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Ramaprasad Talahalli ◽  
Simona Zarini ◽  
Jie Tang ◽  
Guangyuan Li ◽  
Robert Murphy ◽  
...  
Keyword(s):  
Diabetic Mouse ◽  
Retinal Capillary ◽  
Capillary Degeneration

scholarly journals Aryl Hydrocarbon Receptor Agonist VAF347 Impedes Retinal Pathogenesis in Diabetic Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 4335
Author(s):  
Thomas E. Zapadka ◽  
Sarah I. Lindstrom ◽  
Julia C. Batoki ◽  
Chieh A. Lee ◽  
Brooklyn E. Taylor ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Aryl Hydrocarbon Receptor ◽  
Proliferative Diabetic Retinopathy ◽  
Proinflammatory Cytokine ◽  
Primary Source ◽  
Dendritic Cell Maturation ◽  
Diabetic Mice ◽  
Aryl Hydrocarbon ◽  
Aryl Hydrocarbon Receptor Agonist ◽  
Capillary Degeneration

Diabetic retinopathy is the leading cause of blindness in the working-age population worldwide. Although the cause of diabetic retinopathy is multifactorial, IL-17A is a prevalent inflammatory cytokine involved in the promotion of diabetes-mediated retinal inflammation and the progression of diabetic retinopathy. The primary source of IL-17A is Th17 cells, which are T helper cells that have been differentiated by dendritic cells in a proinflammatory cytokine environment. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can manipulate dendritic cell maturation, halt the production of IL-6 (a proinflammatory cytokine), and suppress Th17 cell differentiation. In the current study, we examined the efficacy of an AhR agonist, VAF347, as a potential therapeutic for the onset of non-proliferative diabetic retinopathy in streptozotocin (STZ)-induced diabetic C57BL/6 mice. We determined that diabetes-mediated leukostasis, oxidative stress, and inflammation in the retina of STZ-diabetic mice were all significantly lower when treated with the AhR agonist VAF347. Furthermore, when VAF347 was subcutaneously injected into STZ-diabetic mice, retinal capillary degeneration was ameliorated, which is the hallmark of non-proliferative diabetic retinopathy in this diabetes murine model. Collectively, these findings provide evidence that the AhR agonist VAF347 could be a potentially novel therapeutic for non-proliferative diabetic retinopathy.

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