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CORRECTION OF ISCHEMIC OPTIC NEUROPATHY IN RATS BY CARBAMYLATED DARBEPOETIN

Introduction: The protective effects of carbamylated darbepoetin on the model of ischemic optic neuropathy in rats were revealed.

Objectives: To increase the effectiveness of pharmacological correction of experimental ischemic optic neuropathy in an experiment by using carbamylated darbepoetin.

Methods: Measuring the microcirculation level in the retina of rats was carried out using laser Doppler flowmetry (LDF). Registration was done by the data acquisition system Biopac-systems MP-150 and AcqKnowledge 4.2 programme. For microscopy and morphometry, the prepared microslides were scanned using Mirax Desk, a computerised archiving and image analysis system. Image analysis and morphometry were carried out by Pannoramic Viewer 1.15.4.

Results and discussion: In the group with correction of ischemic optic neuropathy by carbamylated darbepoetin, 300 μg/kg, the microcirculation level increases by 41.9%, p<0.05 in comparison with the control group, but also below the norm values by 20.3%, p<0.05. In the group with correction by recombinant erythropoietin, 50 IU/kg, the microcirculation rate increases by 36.7%, p<0.05 in comparison with the control group and significantly lower - by 23.3%, p<0.05 - in comparison with the group of intact animals. Qualitative and quantitative morphological indices (thickness of retinal layers) helped to reveal a neuroprotective effect of carbamylated darbepoetin to a greater extent than that of recombinant erythropoietin.

Conclusion: The obtained data allow drawing a conclusion about partial restoration of blood flow and preservation of neuronal retinal structures when correcting ischemic optic neuropathy in rats with carbamylated darbepoetin to a greater extent than with recombinant erythropoietin.

Иллюстрации

Table 1. Results of LDF in the Retina in Experimental Animals on 29th Day of the Experiment (M ± m; n = 10).

Note: * – p<0.05 compared with the group of intact animals, у - р<0.05 compared with the control group, PU - perfusion units.

Figure 1. Retinal changes in experimental ischemic optic neuropathy: ( A ) discomplexation of dendrites in the photoreceptor layer and perikaryons in the outer nuclear layer to form intercellular clefts of oedematous type ( B ) discomplexation of structures and oedematous loose shape of inner nuclear (INL) and inner retinal (IRL) layers, pronouncedly full-blooded small vein on the border of the inner retinal and ganglionic layers. Stained with haematoxylin and eosin. x200.

Figure 2. Retinal changes in experimental ischemic optic neuropathy: marked discomplexation of the structure of the photoreceptor (PR) and outer nuclear (ONL) layers; in the photoreceptor layer changes of dendrites of rods and cones through lumpy decomposition. Stained with haematoxylin and eosin. x400.

Figure 3. Details of changes in the optic nerve disc in experimental ischemic optic neuropathy: ( A ) discomplexation of structures in the inner retinal layer (bottom part of the microphoto), pronounced pericellular oedema, lytic changes of individual neurons, plethora and erythrostasis in the venule (arrow) in the ganglionic layer. ( B ) pronounced oedema at the edge of the disc. Stained with haematoxylin and eosin. x200.

Figure 4. Changes in the retina in experimental ischemic optic neuropathy: a focus of pronounced venous plethora (bottom part of the microphoto) of the retina and intraocular haemorrhage; above the arrow is a fragment of a detached internal border glial membrane. Stained with haematoxylin and eosin. x200.

Figure 5. Details of retinal changes in the group with correction by carbamylated darbepoetin: spongiosis of the inner retinal layer (bottom parts of the microphotos), perineuronal oedema in the ganglionic layer (top parts). Stained with haematoxylin and eosin. x400.

Figure 6. Details of retinal changes in the group with correction by recombinant erythropoietin: ( A ) posterior pole of the eye with optic nerve (ON) and posterior retina. The structure of the retinal layers is unchanged; the intraorbital artery is shown by arrow. ( B ) hypertensive changes in the orbital artery (details from Fig. A): uneven intima contours with deformation of the endothelium in the form of “palisade”, dystrophic changes in smooth medial myocytes, destruction of the internal elastic membrane. Stained with haematoxylin and eosin. x200.

Table 2. Thickness of Retinal Layers in Experimental Groups (M ± m).

Note: * – p<0.05 compared with the group of intact animals, у – р<0.05 compared with the control group. CD – group with correction by carbamylated darbepoetin, 300 μg/kg, RE – group with recombinant erythropoietin correction, 50 IU/kg.

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