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… 
View PDF
13 Citations
Highly Influential Citations
1
Background Citations
2

Figures and Tables from this paper

13 Citations

Citation Type

Citation Type

Effect of Topical Administration of Somatostatin on Retinal Inflammation and Neurodegeneration in an Experimental Model of Diabetes
TLDR
It is confirmed that SST topically administered was able to prevent retinal neurodysfunction and neurodegeneration in db/db mice and provides evidence that the neuroprotective effect of SST in diabetic retinas can be largely attributed to anti-inflammatory mechanisms.
Effect of topical administration of the microneurotrophin BNN27 in the diabetic rat retina
TLDR
The results of this study provide solid evidence regarding the efficacy of BNN27 as a neuroprotectant to the diabetic retina when administered topically, and suggest that its pharmacodynamic and pharmacokinetic profiles render it a putative therapeutic for diabetic retinopathy.
SOCS1-Derived Peptide Administered by Eye Drops Prevents Retinal Neuroinflammation and Vascular Leakage in Experimental Diabetes
TLDR
Topical administration of SOCS1-derived peptide is effective in preventing retinal neuroinflammation and early microvascular impairment in a db/db mouse model, and could open up a new strategy for the treatment of early stages of DR.
Targeted pharmacotherapy against neurodegeneration and neuroinflammation in early diabetic retinopathy
Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy
TLDR
Examining the effects of different neuroprotective substances, ranging from nutraceuticals to antioxidants to neuropeptides and others and showing that reducing neuronal suffering also prevents overexpression of VEGF and vascular complications suggests that the use of neuroProtective substances could be an efficient strategy to prevent the onset or to retard the development of DR.
Diabetic Retinopathy: Role of Neurodegeneration and Therapeutic Perspectives.
TLDR
An overview of the main components of neurodegeneration, its key underlying mechanisms, and the more useful experimental models for investigative purposes will be given.
Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets
TLDR
Current perspectives on the pathophysiology of DR as a neurov vascular disease, especially at the early stage are presented and potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed.
Recent Developments in Diabetic Retinal Neurodegeneration: A Literature Review
TLDR
The aim of this article is to highlight the crucial role of neurodegeneration in diabetic retinopathy and to review the molecular basis for this neuronal dysfunction, its diagnostic features, and the progress currently made in relevant therapeutic interventions.
Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy
TLDR
In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before knowledge can be transferred to clinical practice.
Current understanding of the molecular and cellular pathology of diabetic retinopathy
TLDR
The primary focus is on the cellular signalling between the neuronal and vascular retina that promotes formation of the inner blood–retinal barrier of the retinal vasculature as an important point of intervention.
...
...

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.
Attenuation of streptozotocin-induced microvascular changes in the mouse retina with the endothelin receptor A antagonist atrasentan.
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.
...
...