The Role of Catecholamines in the Development of Pathological Retina Neovascularization in an Experimental Model of Retinopathy of Prematurity in Rats.

This work is dedicated to proving our hypothesis that catecholamines and their metabolites play a crucial role in the development of retinopathy of prematurity, which leads to progressive uncontrollable vascularization in the retina, leading to blindness. The study was performed in an animal model of retinopathy of prematurity, which was achieved by hyperoxygenation in rats on postnatal days 7, 14, 21, and 30. The content of catecholamines and their metabolites in the retina of rats was determined by high performance liquid chromatography with electrochemical detection. It was shown that, in the rats with retinopathy, the content of L-DOPA on days 21 and 30 was decreased as compared to the control, whereas the content of noradrenaline on day 14 life increased compared to the control. However, we did not observe changes in the content of dopamine in the experimental animals relative to the control in any period studied. Given the published data on the involvement of catecholamines in the regulation of vasculogenesis in the retina in normal state, our data on the changes in the catecholamine metabolism in the retina in the model of retinopathy of prematurity can be regarded as evidence of the important role of catecholamines in the pathogenesis of this severe disease.

Signal molecules during the organism development: Central and peripheral sources of noradrenaline in rat ontogenesis.

Using the method of high performance liquid chromatography with electrochemical detection, the age dynamics of the content of noradrenaline (NA) in the brain, adrenal gland, and the organ of Zuckerkandl in prenatal (18th and 21st days of embryogenesis) and early postnatal (3, 7, 15, and 30th days) periods of development was studied. The potential contribution of these organs to the formation of physiologically active concentration of noradrenalin in the blood was also assessed. The results suggest that, during the development of the organism, the activity of the sources of noradrenaline in the general circulation changes, which gives a reason to assume the existence of humoral interaction between NA-producing organs in the perinatal period of ontogenesis.

[Reciprocal Humoral Regulation of Endocrine Noradrenaline Sources in Perinatal Development of Rats].

The goal of the present study was to verify our hypothesis of humoral interaction between the norepinephrine secreting organs in the perinatal period of ontogenesis that is aimed at the sustaining of physiologically active concentration of norepinephrine in blood. The objects of the study were the transitory organs, such as brain, organ of Zuckerkandl, and adrenals, the permanent endocrine organ of rats that releases norepinephrine into the bloodstream. To reach this goal, we assessed the adrenal secretory activity (norepinephrine level) and activity of the Zuckerkandl's organ under the conditions of destructed noradrenergic neurons of brain caused by (1) their selective death induced by introduction of a hybrid molecular complex, which consisted of antibodies against dopamine-ß-hydroxylase (DBH) conjugated with saporin cytotoxin (anti-DBH-saporin) into the lateral brain ventricles of neonatal rats; and (2) microsurgical in utero destruction of embryo's brain (in utero encephalectomy). It was observed that 72 h after either pharmacological or microsurgical norepinephrine synthesis deprivation in the newborn rat's brain, the level of norepinephrine was increased in adrenals and, conversely, decreased in the Zuckerkandl's organ. Therefore, the experiments with models of chronical inhibition of norepinephrine synthesis in prenatal and early postnatal rat's brain revealed changes in the secretory activity of peripheral norepinephrine sources. This, apparently, favors the sustaining of physiologically active norepinephrine level in the bloodstream.