THE DEVELOPMENT OF HYPERTENSIVE NEURORETINOPATHY MODEL ON WISTAR RATS
A model of hypertensive neuroretinopathy was developed on Wistar line rats with administration of non-selective NO-synthase blocker N-nitro-L-arginine methyl ester (L-NAME) in a dose 12.5 mg/kg within 28 days on the background of single increased intraocular pressure (IOP) to 110 mmHg. As a result of the interim evaluation of pathology simulation mode the most optimal was a model of hypertensive neuroretinopathy with 5-minute increased IOP at day 26 of the experiment on the background of L-NAME for further study of neuroretinoprotective properties of pharmacological agents. Changes formation of the retina and optic nerve disc (OND), observed in the hypertensive neuroretinopathy, confirmed by ophthalmoscopy, laser Doppler flowmetry (LDF), electroretinography (ERG), histological studies in a group of animals with the pathology modeling at the 29 day of experiment.
Table 1. Methods of integrated semiquantitative evaluation of the fundus changes, detected during ophthalmoscopy (in grades)
Figure 1. Example of ophthalmoscopy on intact Wistar rat. Optic disc is circular or oval shape and stands out from the fundus in pale - pink. The boundaries of the optic nerve disc are clear. It lies in the plane of the retina. From the middle of the optic nerve exit the central vessels of the retina. Blood vessels of the retina don`t have anastomoses. The veins and arteries are straightforward, caliber is uniform, not crimped. The general background is pink.
Figure 2. Example of ophthalmoscopy on Wistar rat with pathology simulation on the background of L-NAME and a single IOP increase within 2 min. Optic disc is round or oval shape and stands out from the fundus of the eye in pink. The boundaries of the OND are clear. It lies in the plane of the retina. There are pockets of "cotton" exudate (arrow + CE). Viens are congested. Arteries are narrowed. Vessel caliber is uneven. Retina is palely (ischemic). Symptom Salus-Hun I (arrow + S I)
Figure 3. Examples of ophthalmoscopy on Wistar rats with pathology simulation on the background of L-NAME and a single IOP increase within 5 min. Optic disc is edematous, increased in size, edema extends to the retina. A slight blurring boundaries of OND. There are pockets of "cotton" exudate (arrow + CE), indicating the growing ischemia. Viens are congested, crimped at the periphery. Arteries are narrowed. Vessel caliber is uneven. Retina is palely (ischemic). Symptom Salus-Hun I (arrow + S I). In rare cases, the solid exudate deposits were observed (arrow + SE)
Figure 4. Pathological changes in the eye on the background of L-NAME administration and single IOP increase within 10 min
Table 2. Integral assessment of fundus changes, detected during ophthalmoscopy (scores 0-5; n = 10)
Table 3. The results of evaluation of retinal electrophysiological state on day 29 of the experiment (M ± m; n = 10), r.u.
Figure 5. Histology of the retina in the group with experimental hypertensive neuroretinopathy: loosening of the layers structure (A), decompaction of location of the outer segments of rods and cones in the photoreceptor layer (Ph), decompaction of perikaryons location of photoreceptor cells in the outer nuclear layer (B). Hematoxylin and eosin. Microphoto. x100 (A), x200 (B)
Figure 6. Changes in retinal layers in the group with experimental hypertensive neuroretinopathy: A - structure decompaction of photoreceptor layer, spheroid and slit-like spaces between the outer segments of the rods and cones, the disorganization of the outer glial limiting membrane (its location indicated by an asterisk), B - loose structure of the outer nuclear layer, hyaline thrombus in the small blood vessel is indicated by the arrow.
Hematoxylin and eosin. Microphoto. x400
Figure 7. Changes in retinal layers in the group with experimental hypertensive neuroretinopathy: A - loose structure. The bundles in the inner nuclear layer, B - loosened structure of the inner retinal layer, expressed pericellular swelling in the ganglion layer (arrow), C - hydropic degeneration of ganglion neurons, capillary stasis with red blood cells in the form of "monetary pillar", the layer of nerve fibers (right part of microphoto) with spongiform changes. Hematoxylin and eosin. Microphoto. x200
Figure 8. Vessels of retinal microcirculatory bed in the experimental group with hypertensive neuroretinopathy: A - plasmatic impregnation phenomenon in the wall of arterioles, B - full-blooded small vein, neuron fragments of ganglion layer with signs of cytolysis (arrow). Hematoxylin and eosin. Microphoto. x200
Figure 9. Severe venous congestion in the inner layers of the retina in the group with experimental hypertensive neuroretinopathy.
Hematoxylin and eosin. Microphoto. x100
Figure 10. Changes in the ganglion layer and retinal nerve fiber layer in the group with experimental hypertensive neuroretinopathy:
A - hydropic dystrophy, cytolytic changes of ganglion neurons, B - chromatolysis, karyopyknosis in the ganglion neurons, spongiform changes in the nerve fiber layer. Hematoxylin and eosin. Microphoto. x200
Figure 11. Heavy neuronal changes in the retinal ganglion layer in the group with experimental hypertensive neuroretinopathy: hydropic degeneration of neurons up to the balloon and total cytolysis, the arrow - a neuron with a total chromatolysis and karyopyknosis. Hematoxylin and eosin. Microphoto. x200
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The development of hypertensive neuroretinopathy model on wistar rats / A.A. Peresypkina, A.A. Dolzhikov, V.O. Gubareva, E.A. Levkova, A.S. Shabelnikova // Research result: pharmacology and clinical pharmacology. – 2017. – Vol. 3, №1 – P. 18-31. DOI: 10.18413/2500-235X-2017-3-1-18-31