Topical Administration of Bosentan Prevents Retinal Neurodegeneration in Experimental Diabetes

@article{Bogdanov2018TopicalAO,
  title={Topical Administration of Bosentan Prevents Retinal Neurodegeneration in Experimental Diabetes},
  author={Patricia Bogdanov and Olga Sim{\'o}-Servat and Joel Sampedro and Cristina Sol{\`a}-Adell and Marta Garc{\'i}a-Ram{\'i}rez and Hugo Ramos and Marta Guerrero and Josep Maria Su{\~n}{\'e}-Negre and Josep Ram{\'o}n Tic{\'o} and Bruno Montoro and Vicente Dur{\'a}n and Luis Arias and Cristina Hern{\'a}ndez and Rafael Sim{\'o}},
  journal={International Journal of Molecular Sciences},
  year={2018},
  volume={19}
}
Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes. The main aim of the present study was to assess the usefulness of… 

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References

SHOWING 1-10 OF 30 REFERENCES
Endothelin Antagonism Prevents Diabetic Retinopathy in NOD Mice: A Potential Role of the Angiogenic Factor Adrenomedullin
TLDR
The therapeutic potential of long-term selective blockade of the ET-1A receptor (ETRA) to prevent the development of retinopathy in a genetic mouse model of nonobese type 1 diabetes is evaluated and ETRA antagonists may provide a novel therapeutic strategy to slow or prevent progression of retinal microvascular damage and proliferation in patients for whom there is clear evidence of activation of theET-1 system.
Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes
TLDR
These findings demonstrate for the first time that CaD exerts neuroprotection in an experimental model of diabetic retinopathy and provide first evidence thatCaD prevents the overexpression of ET-1 and its receptors in the diabetic retina.
Endothelin receptor-A antagonist attenuates retinal vascular and neuroretinal pathology in diabetic mice.
TLDR
Endothelin-A receptor blockade using atrasentan significantly reduces the vascular and neuroretinal complications in diabetic mice and is a promising therapeutic target in diabetic retinopathy.
Effect of Endothelin Dual Receptor Antagonist on VEGF Levels in Streptozotocin-Induced Diabetic Rat Retina
TLDR
It is concluded that an ETA/B dual receptor antagonist could reverse the expression level of VEGF in the diabetic retina while failing to normalize the upregulated ICAM-1 expression.
Diabetes-induced vascular dysfunction in the retina: role of endothelins
TLDR
The results from this study indicate that the endothelin system is of importance in mediating retinal changes in diabetes although mechanisms of the endethelin system alteration as well as their effects might vary depending on the duration of diabetes.
Role of the ETB receptor in retinal ganglion cell death in glaucoma.
TLDR
It is suggested that ocular ET-1 acts through ETB receptors to mediate apoptosis of retinal ganglion cells, a key event in glaucoma and related optic neuropathies.
An Endothelin Type A Receptor Antagonist Reverses Upregulated VEGF and ICAM-1 Levels in Streptozotocin-Induced Diabetic Rat Retina
TLDR
ETA receptor antagonist might be useful in preventing the progression of diabetic retinopathy, as evidenced by suppressing the increase in VEGF and ICAM-1 levels as well as leukostasis in morphologically intact diabetic retina.
Blocking endothelin-B receptors rescues retinal ganglion cells from optic nerve injury through suppression of neuroinflammation.
TLDR
Results suggest that the microglia/macrophages recruited to the crushed site are the possible cellular sources of the ETs, which caused reciprocal activation of astrocytes.
Endothelin B Receptors Contribute to Retinal Ganglion Cell Loss in a Rat Model of Glaucoma
TLDR
Elevated intraocular pressure mediated increase in ETB receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma, raising the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glAUcoma.
...
...