Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat

Varga, Balázs; Priksz, Dániel; Lampé, Nóra; Bombicz, Mariann; Kurucz, Andrea; Szabó, Ágnes; Pósa, Anikó; Szabó, Renáta; Kemény-Beke, Ádám; Remenyik, Judit; Gesztelyi, Rudolf; Juhász, Béla

doi:10.3390/molecules22101782

Cited by 17 publications

(15 citation statements)

References 37 publications

(53 reference statements)

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“…As we demonstrated such massive retinal injury, it can be assumed that the used dose and application type had no protective effects on the ischemic-induced damage in our study. Moreover, ketamine/xylazine is a common anesthesia for the induction of I/R in rodents (Unoki and LaVail, 1994; Produit-Zengaffinen et al, 2009; Abcouwer et al, 2010; David et al, 2011; Kara et al, 2014; Varga et al, 2017; Lin et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

From Ganglion Cell to Photoreceptor Layer: Timeline of Deterioration in a Rat Ischemia/Reperfusion Model

Palmhof

Frank

Rappard

et al. 2019

Front. Cell. Neurosci.

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Neuronal damage and impaired vision in different retinal disorders are induced, among other factors, by ischemia/reperfusion (I/R). Since the mechanisms and the progression of ischemic injury are still not completely clarified, a timeline of this retinal degeneration is needed. In this study, we investigated protein and mRNA alterations at 2, 6, 12, and 24 h as well as 3 and 7 days after ischemia to determine the course of an ischemic insult through the whole retina. Moreover, functional analyses were performed at later stages. We detected a significant functional loss of cells in the inner nuclear layer and photoreceptors at 3 and 7 days. Additionally, the thickness of the whole retina was decreased at these points in time, indicating a severe degradation of all retinal layers. Immunohistological and qRT-PCR analyses of retinal ganglion cells (RGCs), glial cells, AII amacrine, cone and rod bipolar as well as cone and rod photoreceptor cells confirmed this first assumption. Our results show that all investigated cell types were damaged by ischemia induction. Especially RGCs, cone bipolar cells, and photoreceptor cones are very sensitive to I/R. These cells were lost shortly after ischemia induction with a progressive course up to 7 days. In addition, Müller cell gliosis was observed over the entire period of time. These results provide evidence, that I/R induces damage of the whole retina at early stages and increases over time. In conclusion, our study could demonstrate the intense impact of an ischemic injury. The ischemic defect spreads across the whole retina right up to the outer layers in the long-term and thus seems to impair the visual perception already during the stimulus processing. In addition, our findings indicate that the cone pathway seems to be particularly affected by this damage.

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Section: Discussionmentioning

confidence: 99%

From Ganglion Cell to Photoreceptor Layer: Timeline of Deterioration in a Rat Ischemia/Reperfusion Model

Palmhof

Frank

Rappard

et al. 2019

Front. Cell. Neurosci.

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“…One day before the extermination of the animals electroretinographical assessments were carried out according to a formerly used method [3] as follows. The animals were anaesthetized by a mixture of ketamin/xylazine (100/10 mg/kg), followed by the administration of cyclopentolate for pupil dilation (Humapent, Teva Ltd., Debrecen, Hungary), one drop in each eye.…”

Section: Eletroretinographymentioning

confidence: 99%

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone

Wachal

Bombicz

Priksz

et al. 2020

IJMS

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High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements—like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results—electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.

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“…Electrical activity of both eyes of each animal were measured following 10 flash stimuli to create a common pool of recordings for each group, from which statistics were carried out as detailed in "Statistical Analysis" section. Former results of the authors with the same recording system assure that the used experimental method provides reproducible and reliable data on functioning of the retina, correlating with retinal integrity (Varga et al, 2011;Varga et al, 2013;Varga et al, 2017;Wachal et al, 2020).…”

Section: Electroretinographymentioning

confidence: 87%

“…Functioning of the retina produces electric signals which are deteriorated in diabetes due to microcirculatory problems (Varga et al, 2017;Danis and Yang, 1993). Thus, the effect of BGP-15 seen in our electroretinographical results (Figure 5) might be connected to lessening of such microcirculatory complications.…”

Section: Discussionmentioning

confidence: 99%

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment

et al. 2021

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Retinal complications of diabetes often lead to deterioration or even loss of vision. This hastens discovery of pharmacological agents able to counterbalance diabetic retinopathy. BGP-15, an emerging small molecule agent, was formerly proven by our workgroup to be retinoprotective on nonobese diabetic animals, Goto-Kakizaki rats. In the present study, we aimed to examine its long-term tolerability or incidental side effects on obese-prone Zucker diabetic fatty (ZDF) rats to further increase the rationale for a future human translation. To make terminal visual status comparable with our other investigations, we also carried out electroretinography (ERG) at the end of the experiment. Our study was started on 16-week-old ZDF rats and lasted for 52 weeks, while BGP was administered daily by gavage. During the 12 months of treatment, 100% of BGP-treated animals survived compared to the non-treated ZDF group, where 60% of the animals died, which was a statistically significant difference. Based on ERG results, BGP-15 was able to counterbalance visual deterioration of ZDF rats caused by long-term diabetes. Some moderate but significant changes were seen in OGTT results and some relationship to oxidative stress by the western blot method: BGP-15 was able to increase expression of HSP70 and decrease that of NFkB in eyes of rats. These were in concert with our previous observations of SIRT1 increment and MMP9 decrement in diabetic eyes by BGP. In summary, not only is BGP-15 not harmful in the long run but it is even able to reduce the related mortality and the serious consequences of diabetes. BGP-15 is an excellent candidate for future drug development against diabetic retinopathy.

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Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat

Cited by 17 publications

References 37 publications

From Ganglion Cell to Photoreceptor Layer: Timeline of Deterioration in a Rat Ischemia/Reperfusion Model

From Ganglion Cell to Photoreceptor Layer: Timeline of Deterioration in a Rat Ischemia/Reperfusion Model

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment

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