Pharmacological correction of morphofunctional retinal injury using 11-amino acid fragment of darbepoetin in the experiment

Autor: Victoria O. Gubareva, Anton L. Pazhinsky, Sergey S. Lugovskoy, Elizaveta Yu. Dubovtsova, Daria S. Vain, Anna S. Pobeda, Konstantin N. Pasenov
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Research Results in Pharmacology, Vol 5, Iss 3, Pp 43-55 (2019)
Druh dokumentu: article
ISSN: 2658-381X
DOI: 10.3897/rrpharmacology.5.38730
Popis: Introduction: The retinoprotective effect of the 11-amino acid fragment of darbepoetin PRK-002 on the models of hypertensive retinal angiopathy and hypertensive neuroretinopathy in Wistar rats was investigated in comparison with carbamylated darbepoetin and sulodexide. Materials and methods: The protective effects of the pharmacological agents were assessed using the following criteria: a semi-quantitative assessment of changes in the eye fundus when performing ophthalmoscopy, the retinal blood flow, the b/a coefficient, eNOs expression in retinal vessels, specific number of neuronal nuclei in the inner nuclear layer, and p53 expression in the retina. Results and discussion: A pronounced protective effect, exceeding sulodexide at a dose of 150 LRU/kg and carbamylated darbepoetin at a dose of 300 μg/kg when correcting retinal angiopathy was observed in PRK-002 at a dose of 4 µg/kg, which expressed in adjustment of the retinal vessels’ calibers, removing retinal arterio-venous crossings, reaching the target levels of the retinal microcirculation, the b/a coefficient, and the restoration of eNOs expression in the endothelium of retinal vessels. PRK-002 at a dose of 4 µg/kg has a pronounced neuroprotective effect comparable to carbamylated darbepoetin at a dose of 300 µg/kg in correction of hypertensive neuroretinopathy, which expressed in the normalization of the fundus image, reaching the b/a target values, the specific number of neuronal nuclei in the inner nuclear layer, inhibition of p53 expression in the neurons of the inner nuclear and ganglionic layers. Conclusion: The study revealed angio- and neuroprotective activity of the 11-amino acid fragment of darbepoetin PRK-002 in correction of retinal injury formed on the background of hypertension.
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