Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model

Palmhof, Marina; Lohmann, Stephanie; Schulte, Dietmar; Stute, Gesa; Wagner, Natalie; Dick, H. Burkhard; Joachim, Stephanie C.

doi:10.3390/ijms19061636

Cited by 27 publications

(30 citation statements)

References 51 publications

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“…Retinal ischemia is related to the atherosclerosis of retinal vessels and carotid arteries, diabetic retinopathy, glaucoma, and endocrine ophthalmopathy [3,4]. Retinal ischemia leads to an increase in the content of impaired metabolism products which, over time, can lead to atrophy of the optic nerve [5,6]. High intraocular pressure (IOP) cuts the supply of oxygen and glucose, subsequently leading to the induction of apoptosis and retinal cell death [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

Peresypkina

Pazhinsky

Даниленко

et al. 2020

Biology

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An important task of pharmacology is to find effective agents to improve retinal microcirculation and resistance to ischemia. The purpose of the study is to pharmacologically evaluate the retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate in a rat model of retinal ischemia–reperfusion. A retinal ischemia–reperfusion model was used, in which an increase in intraocular pressure (IOP) to 110 mmHg was carried out within 30 min. The retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate at a dose of 3.8 mg/kg, in comparison with nicotinic acid at a dose of 2 mg/kg and emoxipine at a dose of 2 mg/kg, was estimated by the changes in the eye fundus during ophthalmoscopy, the retinal microcirculation level with laser Doppler flowmetry (LDF), and electroretinography (ERG) after 72 h of reperfusion. The use of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate prevented the development of ischemic injuries in the fundus and led to an increase in the retinal microcirculation level to 747 (median) (lower and upper quartiles: 693;760) perfusion units (p = 0.0002) in comparison with the group that underwent no treatment. In the group with the studied substance, the b-wave amplitude increased significantly (p = 0.0022), and the b/a coefficient increased reliably (p = 0.0002) in comparison with the group with no treatment. Thus, 2-ethyl-3-hydroxy-6-methylpyridine nicotinate has established itself as a potential retinoprotector.

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Section: Introductionmentioning

confidence: 99%

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

Peresypkina

Pazhinsky

Даниленко

et al. 2020

Biology

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“…), organ-histological, and microcirculatory. Ischemia leads to the accumulation of impaired metabolism products in the retina, which subsequently leads to dystrophy, up to atrophy, of the optic nerve, in the first place (Huang et al 2018, Palmhof et al 2018.…”

Section: Resultsmentioning

confidence: 99%

Correction of retinal ischemic injuries by using non-selective imidazoline receptor agonists in the experiment

Levkova¹,

Pazhinsky²,

Lugovskoy³

et al. 2019

RRP

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Introduction:Retinoprotective effects of non-selective imidazoline receptor agonists: potassium salt of С7070; sodium salt of С7070; С7070 processed with CO 2 -were investigated in comparison with C7070 on the retinal ischemia-reperfusion model in rats. Materials and methods:The protective effects of the substances were evaluated by using ophthalmoscopy, laser Doppler flowmetry, electroretinography, histological and morphometric studies of retinal layers. Results and discussion:The most pronounced retinoprotective effect was observed in potassium salt of C7070 at a dose of 10 mg/kg, which expresses in approaching the normal eye fundus image, achieving the target values of the retinal blood flow, b/a coefficient, and reaching the norm values of morphometric indicators. A less pronounced protective effect was found in sodium salt of C7070 at a dose of 10 mg/kg, which expresses in a 71% decrease (p < 0.05) in semi-quantitative assessment of the eye fundus changes, an increase in the retinal blood flow level by 70.4% (p < 0.05), in b/a by 94% (p < 0.05) in comparison with the group without correction, and reaching the norm of the morphometric indicators. A retinoprotective effect of the substance C7070 processed with CO 2 at a dose of 10 mg/kg is inferior to that of the sodium salt of C7070. Conclusion:The retinoprotective activity of the substances is expressed in descending order: potassium salt of С7070 (10 mg/kg) ≈ С7070 (50 mg/kg) > sodium salt of С7070 (10 mg/kg) > С7070 processed with CO 2 (10 mg/kg) ≈ С7070 (10 mg/kg). Injections of glibenclamide leveled the neuroretinoprotective effects of the substances to varying degrees, which confirmed the participation of ATP-dependent potassium channels in the implementation of these effects.

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“…However, the molecular mechanism on how anti-VEGF therapy improves ischemia and realizes reperfusion remains unclear. A study using retinal ischemia animal models proved that anti-VEGF therapy could reduce autophagy and apoptosis rate and activate ischemia-damaged microglia to protect the retinal ganglion cells and bipolar cells [30]. In another study on tumor, VEGF inhibition can normalize peripheral cells, stabilize the basement membrane, remodel the immature vessels to a more mature version by destroying the vessels that lack peripheral cells, and provide frameworks for new vessels to grow in again by stabilizing the basement membrane.…”

Section: Discussionmentioning

confidence: 99%

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography

et al. 2020

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Background Varying degrees of macular ischemia generally occur in diabetic retinopathy (DR). This study aims to evaluate the effect of conbercept with 3+ pro re nata (PRN) on macular perfusion status in patients with diabetic macular edema (DME) and quantitatively assess changes in foveal avascular zone (FAZ) areas and capillary density in macular regions by applying optical coherence tomography angiography (OCTA). Methods Fifty patients were divided into ischemic (n = 31) and non-ischemic (n = 19) groups according to the presence of ischemia on OCTA at baseline. All patients received intravitreal injections of 0.5 mg of conbercept with 3+ PRN principle. The FAZ areas and macular vessel density measured using OCTA were evaluated at baseline, 3 months, and 6 months after treatment in both groups. Results At months 3 and 6, the FAZ area in the ischemic group changed from 0.510 ± 0.171 mm2 to 0.441 ± 0.158 mm2 then to 0.427 ± 0.153 mm2 (p = 0.003, p = 0.296); in the non-ischemic group, it remained stable (p = 0.269, p = 0.926). The superficial vessel density changed from 41.1 ± 4.1 to 42.5% ± 4.7% then to 42.6% ± 4.6% (p = 0.043, p = 0.812), and the deep vessel density changed from 40.7 ± 4.4 to 42.3% ± 3.6% then to 42.3% ± 4.7% (p = 0.072, p = 0.961) in the ischemic group. In the non-ischemic group, the superficial vessel density changed from 44.8 ± 3.2 to 46.0% ± 3.5% then to 45.7% ± 3.3% (p = 0.108, p = 0.666), whereas the deep vessel density changed from 43.6 ± 3.6 to 43.8% ± 3.2% then to 43.5% ± 4.5% (p = 0.882, p = 0.736). Reperfusion in macular nonperfusion areas was observed. Conclusion Anti–vascular endothelial growth factor treatment may have a positive effect on macular perfusion status. Furthermore, OCTA had advantages in quantifying and calculating blood flow index in the study of macular perfusion status.

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Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model

Cited by 27 publications

References 51 publications

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

Correction of retinal ischemic injuries by using non-selective imidazoline receptor agonists in the experiment

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography

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