Robert Gábriel - Academia.edu (original) (raw)

Papers by Robert Gábriel

Research paper thumbnail of Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development

International Journal of Molecular Sciences, 2021

It is well established that miR-9 contributes to retinal neurogenesis. However, little is known a... more It is well established that miR-9 contributes to retinal neurogenesis. However, little is known about its presence and effects in the postnatal period. To expand our knowledge, miRNA-small RNA sequencing and in situ hybridization supported by RT-qPCR measurement were carried out. Mir-9 expression showed two peaks in the first three postnatal weeks in Wistar rats. The first peak was detected at postnatal Day 3 (P3) and the second at P10, then the expression gradually decreased until P21. Furthermore, we performed in silico prediction and established that miR-9 targets OneCut2 or synaptotagmin-17. Another two microRNAs (mir-135, mir-218) were found from databases which also target these proteins. They showed a similar tendency to mir-9; their lowest expression was at P7 and afterwards, they showed increase. We revealed that miR-9 is localized mainly in the inner retina. Labeling was observed in ganglion and amacrine cells. Additionally, horizontal cells were also marked. By dual miRNA...

Research paper thumbnail of Profile of miR-23 Expression and Possible Role in Regulation of Glutamic Acid Decarboxylase during Postnatal Retinal Development

International Journal of Molecular Sciences, 2021

As neurotransmitter, GABA is fundamental for physiological processes in the developing retina. It... more As neurotransmitter, GABA is fundamental for physiological processes in the developing retina. Its synthesis enzymes are present during retinal development, although the molecular regulatory mechanisms behind the changes in expression are not entirely understood. In this study, we revealed the expression patterns of glutamic acid decarboxylase 67(GAD67) and its coding gene (GAD1) and its potential miRNA-dependent regulation during the first three postnatal weeks in rat retina. To gain insight into the molecular mechanisms, miRNA-sequencing supported by RT-qPCR and in situ hybridization were carried out. GAD1 expression shows an increasing tendency, peaking at P15. From the in silico-predicted GAD1 targeting miRNAs, only miR-23 showed similar expression patterns, which is a known regulator of GAD1 expression. For further investigation, we made an in situ hybridization investigation where both GAD67 and miR-23 also showed lower expression before P7, with the intensity of expression gr...

Research paper thumbnail of PACAP for Retinal Health: Model for Cellular Aging and Rescue

International Journal of Molecular Sciences, 2021

Retinal aging is the result of accumulating molecular and cellular damage with a manifest decline... more Retinal aging is the result of accumulating molecular and cellular damage with a manifest decline in visual functions. Somatostatin (SST) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been implicated in neuroprotection through regulating disparate aspects of neuronal activity (survival, proliferation and renewal). The aim of the present study was to validate a transgenic model for SST-expressing amacrine cells and to investigate the chronic effect of PACAP on the aging of SSTergic and dopaminergic cells of the retina. SST-tdTomato transgenic mice that were 6, 12 and 18 months old were treated intravitreally with 100 pmol of PACAP every 3 months. The density of SST and dopaminergic amacrine cells was assessed in whole-mounted retinas. Cells displaying the transgenic red fluorescence were identified as SST-immunopositive amacrine cells. By comparing the three age groups. PACAP treatment was shown to induce a moderate elevation of cell densities in both the SST an...

Research paper thumbnail of Novel Neuroprotective Strategies in Ischemic Retinal Lesions

International Journal of …, 2010

Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusio... more Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K + channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques.

Research paper thumbnail of Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration

Neurotoxicity Research, 2007

Diazoxide (DIAZ) has been shown to be neuroprotective in animal models of different brain patholo... more Diazoxide (DIAZ) has been shown to be neuroprotective in animal models of different brain pathologies. However, the direct protective effect of DIAZ in different in vivo models of retinal degeneration has not yet been shown. Therefore, the aim of the present study was to investigate the neuroprotective role of this compound in two rodent model systems: monosodium-glutamate (MSG)-and chronic bilateral carotid artery occlusion (BCAO)-induced retinal degeneration. Rats were subjected either to s.c. MSG treatment on postnatal days 1, 5 and 9, or to BCAO at 2 months of age, followed by intravitreal DIAZ treatment. Histological examination was carried out 14 or 21 days after treatments, respectively. MSG treatment destroyed almost the entire inner retina, with the inner nuclear and ganglion cell layers being fused. DIAZ treatment significantly ameliorated the MSG-induced retinal degeneration. BCAO led to a severe degeneration of all retinal layers, and DIAZ proved to be protective also in this model. Our results may have clinical implications in reducing glutamate-induced excitotoxicity or ischemic retinal degeneration in ophthalmic diseases.

Research paper thumbnail of Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development

International Journal of Molecular Sciences, 2021

It is well established that miR-9 contributes to retinal neurogenesis. However, little is known a... more It is well established that miR-9 contributes to retinal neurogenesis. However, little is known about its presence and effects in the postnatal period. To expand our knowledge, miRNA-small RNA sequencing and in situ hybridization supported by RT-qPCR measurement were carried out. Mir-9 expression showed two peaks in the first three postnatal weeks in Wistar rats. The first peak was detected at postnatal Day 3 (P3) and the second at P10, then the expression gradually decreased until P21. Furthermore, we performed in silico prediction and established that miR-9 targets OneCut2 or synaptotagmin-17. Another two microRNAs (mir-135, mir-218) were found from databases which also target these proteins. They showed a similar tendency to mir-9; their lowest expression was at P7 and afterwards, they showed increase. We revealed that miR-9 is localized mainly in the inner retina. Labeling was observed in ganglion and amacrine cells. Additionally, horizontal cells were also marked. By dual miRNA...

Research paper thumbnail of Profile of miR-23 Expression and Possible Role in Regulation of Glutamic Acid Decarboxylase during Postnatal Retinal Development

International Journal of Molecular Sciences, 2021

As neurotransmitter, GABA is fundamental for physiological processes in the developing retina. It... more As neurotransmitter, GABA is fundamental for physiological processes in the developing retina. Its synthesis enzymes are present during retinal development, although the molecular regulatory mechanisms behind the changes in expression are not entirely understood. In this study, we revealed the expression patterns of glutamic acid decarboxylase 67(GAD67) and its coding gene (GAD1) and its potential miRNA-dependent regulation during the first three postnatal weeks in rat retina. To gain insight into the molecular mechanisms, miRNA-sequencing supported by RT-qPCR and in situ hybridization were carried out. GAD1 expression shows an increasing tendency, peaking at P15. From the in silico-predicted GAD1 targeting miRNAs, only miR-23 showed similar expression patterns, which is a known regulator of GAD1 expression. For further investigation, we made an in situ hybridization investigation where both GAD67 and miR-23 also showed lower expression before P7, with the intensity of expression gr...

Research paper thumbnail of PACAP for Retinal Health: Model for Cellular Aging and Rescue

International Journal of Molecular Sciences, 2021

Retinal aging is the result of accumulating molecular and cellular damage with a manifest decline... more Retinal aging is the result of accumulating molecular and cellular damage with a manifest decline in visual functions. Somatostatin (SST) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been implicated in neuroprotection through regulating disparate aspects of neuronal activity (survival, proliferation and renewal). The aim of the present study was to validate a transgenic model for SST-expressing amacrine cells and to investigate the chronic effect of PACAP on the aging of SSTergic and dopaminergic cells of the retina. SST-tdTomato transgenic mice that were 6, 12 and 18 months old were treated intravitreally with 100 pmol of PACAP every 3 months. The density of SST and dopaminergic amacrine cells was assessed in whole-mounted retinas. Cells displaying the transgenic red fluorescence were identified as SST-immunopositive amacrine cells. By comparing the three age groups. PACAP treatment was shown to induce a moderate elevation of cell densities in both the SST an...

Research paper thumbnail of Novel Neuroprotective Strategies in Ischemic Retinal Lesions

International Journal of …, 2010

Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusio... more Retinal ischemia can be effectively modeled by permanent bilateral common carotid artery occlusion, which leads to chronic hypoperfusion-induced degeneration in the entire rat retina. The complex pathways leading to retinal cell death offer a complex approach of neuroprotective strategies. In the present review we summarize recent findings with different neuroprotective candidate molecules. We describe the protective effects of intravitreal treatment with: (i) urocortin 2; (ii) a mitochondrial ATP-sensitive K + channel opener, diazoxide; (iii) a neurotrophic factor, pituitary adenylate cyclase activating polypeptide; and (iv) a novel poly(ADP-ribose) polymerase inhibitor (HO3089). The retinoprotective effects are demonstrated with morphological description and effects on apoptotic pathways using molecular biological techniques.

Research paper thumbnail of Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration

Neurotoxicity Research, 2007

Diazoxide (DIAZ) has been shown to be neuroprotective in animal models of different brain patholo... more Diazoxide (DIAZ) has been shown to be neuroprotective in animal models of different brain pathologies. However, the direct protective effect of DIAZ in different in vivo models of retinal degeneration has not yet been shown. Therefore, the aim of the present study was to investigate the neuroprotective role of this compound in two rodent model systems: monosodium-glutamate (MSG)-and chronic bilateral carotid artery occlusion (BCAO)-induced retinal degeneration. Rats were subjected either to s.c. MSG treatment on postnatal days 1, 5 and 9, or to BCAO at 2 months of age, followed by intravitreal DIAZ treatment. Histological examination was carried out 14 or 21 days after treatments, respectively. MSG treatment destroyed almost the entire inner retina, with the inner nuclear and ganglion cell layers being fused. DIAZ treatment significantly ameliorated the MSG-induced retinal degeneration. BCAO led to a severe degeneration of all retinal layers, and DIAZ proved to be protective also in this model. Our results may have clinical implications in reducing glutamate-induced excitotoxicity or ischemic retinal degeneration in ophthalmic diseases.