A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...
1. Retinal electrical synapses team: Prof. Dr. Béla Völgyi, Dr. Tamás Kovács-Öller, Gergely Szarka, Márton Balogh, Boglarka Balogh
Over 85% of the information perceived by our nervous system is processed by the retina, thus it is essential to understand how the retinal neuronal hyper-network works. Electrical synapses have been known for some 40 years, however their crucial role in visual information processing has only become obvious in recent years. Our team performs experiments to show that electrically coupled retinal neuronal networks play important roles in higher visual functions. We examine the expressional changes of the gap junction forming connexin proteins during the postnatal development and/or induced by changes in the environment. Our work particularly focuses on those inner retinal gap junctions that are formed by ganglion and amacrine cells (ganglion-ganglion, amacrine-amacrine and amacrine-ganglion) and participate in the synchronization of ganglion cell action potentials. We study how such ganglion cell population activity encodes certain visual patterns or visual cues. We also study how the function of electrical and chemical synapses affect each other and if they interfere and/or cooperate to serve signaling. Results of our research will contribute to algorithms for the stimulation of retinal prostheses and/or to provide data to design high performance bionic eyes for robotics.
Alumni: Dr. Ádám Tengölics, László Albert, Gábor Debertin PhD, Anikó Óhidi-Légmán, Erica Popovich, Adrienn Szabó, Dániel Varga
2. Retinal signalization team: Prof. Dr. Róbert Gábriel, Dr. Andrea Kovács-Valasek, Dr. Alma Ganczer
Our research focus is to expand our knowledge on the mechanisms of metabolic retinal degenerations by exploiting experimental work with animal models. We explore how metabolic mechanisms that mediate human retinal degenerations induce retinal cell loss, and which biochemical signaling pathways are involved in mechanisms that eventually impair vision. Our results will reveal the potential rescue mechanisms to avoid retinal degeneration by blocking the degeneration pathways or by enhancing mechanisms that serve neuronal protection. The knowledge on this latter issue will allow us to test and design new pharmacological compounds. Throughout these experiments we will also gain information on the mechanisms of retinal information processing, neuronal degeneration and neuronal protection.
Retinal electrical synapses team:
Chhatwal S, Antony H, Lamei S, Kovács-Öller T, Klettner AK, Zille M. A systematic review of the cell death mechanisms in retinal pigment epithelium cells and photoreceptors after subretinal hemorrhage - Implications for treatment options. Biomed Pharmacother. 2023 Sep 22;167:115572. doi: 10.1016/j.biopha.2023.115572. Epub ahead of print. PMID: 37742603.
Kovács-Öller T, Szarka G, Hoffmann G, Péntek L, Valentin G, Ross L, Völgyi B. Extrinsic and Intrinsic Factors Determine Expression Levels of Gap Junction- Forming Connexins in the Mammalian Retina. Biomolecules. 2023 Jul 13;13(7):1119. doi: 10.3390/biom13071119. PMID: 37509155; PMCID: PMC10377540.
Kovács-Öller T, Völgyi B. Molecular Mechanisms of Retinal Degeneration and How to Avoid It. Int J Mol Sci. 2023 May 15;24(10):8752. doi: 10.3390/ijms24108752. PMID: 37240098; PMCID: PMC10218442.
Kovács-Öller T, Zempléni R, Balogh B, Szarka G, Fazekas B, Tengölics ÁJ, Amrein K, Czeiter E, Hernádi I, Büki A, Völgyi B. Traumatic Brain Injury Induces Microglial and Caspase3 Activation in the Retina. Int J Mol Sci. 2023 Feb 23;24(5):4451. doi: 10.3390/ijms24054451. PMID: 36901880; PMCID: PMC10003323.
Kovács-Öller T, Dedek K, Hillier D. Editorial: Visual code: From the retina to the brain. Front Cell Neurosci. 2022 Sep 14;16:1018229. doi: 10.3389/fncel.2022.1018229. PMID: 36187292; PMCID: PMC9516390.
Ganczer A, Szarka G, Balogh M, Hoffmann G, Tengölics ÁJ, Kenyon G, Kovács- Öller T, Völgyi B. Transience of the Retinal Output Is Determined by a Great Variety of Circuit Elements. Cells. 2022 Feb 25;11(5):810. doi: 10.3390/cells11050810. PMID: 35269432; PMCID: PMC8909309.
Balogh B, Szarka G, Tengölics ÁJ, Hoffmann G, Völgyi B, Kovács-Öller T. LED-Induced Microglial Activation and Rise in Caspase3 Suggest a Reorganization in the Retina. Int J Mol Sci. 2021 Sep 27;22(19):10418. doi: 10.3390/ijms221910418. PMID: 34638759; PMCID: PMC8508983.
Fusz K, Kovács-Öller T, Kóbor P, Szabó-Meleg E, Völgyi B, Buzás P, Telkes I. Regional Variation of Gap Junctional Connections in the Mammalian Inner Retina. Cells. 2021 Sep 12;10(9):2396. doi: 10.3390/cells10092396. PMID: 34572046; PMCID: PMC8466939.
Szarka G, Balogh M, Tengölics ÁJ, Ganczer A, Völgyi B, Kovács-Öller T. The role of gap junctions in cell death and neuromodulation in the retina. Neural Regen Res. 2021 Oct;16(10):1911-1920. doi: 10.4103/1673-5374.308069. PMID: 33642359; PMCID: PMC8343308.
Völgyi B. Molecular Biology of Retinal Ganglion Cells. Cells. 2020 Nov 15;9(11):2483. doi: 10.3390/cells9112483. PMID: 33203148; PMCID: PMC7697858.
Wang Q, Banerjee S, So C, Qiu C, Lam HC, Tse D, Völgyi B, Pan F. Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model. FASEB J. 2020 Nov;34(11):15282-15299. doi: 10.1096/fj.202001315RR. Epub 2020 Sep 28. PMID: 32985731.
Kovacs-Oller T, Ivanova E, Bianchimano P, Sagdullaev BT. The pericyte connectome: spatial precision of neurovascular coupling is driven by selective connectivity maps of pericytes and endothelial cells and is disrupted in diabetes. Cell Discov 6, 39 (2020). https://doi.org/10.1038/s41421-020-0180-0
Kovács-Öller T, Ivanova E, Szarka G, Tengölics ÁJ, Völgyi B, Sagdullaev BT. Imatinib Sets Pericyte Mosaic in the Retina. Int J Mol Sci. 2020 Apr 5;21(7):2522. doi: 10.3390/ijms21072522. PMID: 32260484; PMCID: PMC7177598.
Kovács-Öller T, Szarka G, Tengölics ÁJ, Ganczer A, Balogh B, Szabó-Meleg E, Nyitrai M, Völgyi B. Spatial Expression Pattern of the Major Ca2+-Buffer Proteins in Mouse Retinal Ganglion Cells. Cells. 2020 Mar 25;9(4):792. doi: 10.3390/cells9040792. PMID: 32218175; PMCID: PMC7226302.
Tengölics ÁJ, Szarka G, Ganczer A, Szabó-Meleg E, Nyitrai M, Kovács-Öller T, Völgyi B. Response Latency Tuning by Retinal Circuits Modulates Signal Efficiency. Sci Rep. 2019 Oct 22;9(1):15110. doi: 10.1038/s41598-019-51756-y. PMID: 31641196; PMCID: PMC6806000.
Völgyi B, Kenyon GT, Marshak DW, Sagdullaev B. Editorial: Encoding Visual Features by Parallel Ganglion Cell Initiated Pathways in the Healthy, Diseased and Artificial Retina. Front Cell Neurosci. 2019 May 24;13:229. doi: 10.3389/fncel.2019.00229. PMID: 31178700; PMCID: PMC6542953.
Telkes I, Kóbor P, Orbán J, Kovács-Öller T, Völgyi B, Buzás P. Connexin-36 distribution and layer-specific topography in the cat retina. Brain Struct Funct. 2019 Jul;224(6):2183-2197. doi: 10.1007/s00429-019-01876-y. Epub 2019 Jun 6. PMID: 31172263; PMCID: PMC6591202.
Kovács-Öller T, Szarka G, Ganczer A, Tengölics Á, Balogh B, Völgyi B. Expression of Ca2+-Binding Buffer Proteins in the Human and Mouse Retinal Neurons. Int J Mol Sci. 2019 May 7;20(9):2229. doi: 10.3390/ijms20092229. PMID: 31067641; PMCID: PMC6539911.
Kántor O, Szarka G, Benkő Z, Somogyvári Z, Pálfi E, Baksa G, Rácz G, Nitschke R, Debertin G, Völgyi B. Strategic Positioning of Connexin36 Gap Junctions Across Human Retinal Ganglion Cell Dendritic Arbors. Front Cell Neurosci. 2018 Nov 22;12:409. doi: 10.3389/fncel.2018.00409. PMID: 30524239; PMCID: PMC6262005.
Ganczer A, Balogh M, Albert L, Debertin G, Kovács-Öller T, Völgyi B. Transiency of retinal ganglion cell action potential responses determined by PSTH time constant. PLoS One. 2017 Sep 12;12(9):e0183436. doi: 10.1371/journal.pone.0183436. PMID: 28898257; PMCID: PMC5595288.
Kovács-Öller T, Debertin G, Balogh M, Ganczer A, Orbán J, Nyitrai M, Balogh L, Kántor O, Völgyi B. Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison. Front Cell Neurosci. 2017 Mar 9;11:65. doi: 10.3389/fncel.2017.00065. PMID: 28337128; PMCID: PMC5343066.
Kántor O, Varga A, Nitschke R, Naumann A, Énzsöly A, Lukáts Á, Szabó A, Németh J, Völgyi B. Bipolar cell gap junctions serve major signaling pathways in the human retina. Brain Struct Funct. 2017 Aug;222(6):2603-2624. doi: 10.1007/s00429-016-1360-4. Epub 2017 Jan 10. PMID: 28070649.
Pan F, Toychiev A, Zhang Y, Atlasz T, Ramakrishnan H, Roy K, Völgyi B, Akopian A, Bloomfield SA. Inhibitory masking controls the threshold sensitivity of retinal ganglion cells. J Physiol. 2016 Nov 15;594(22):6679-6699. doi: 10.1113/JP272267. Epub 2016 Aug 2. PMID: 27350405; PMCID: PMC5108909.
Kántor O, Mezey S, Adeghate J, Naumann A, Nitschke R, Énzsöly A, Szabó A, Lukáts Á, Németh J, Somogyvári Z, Völgyi B. Calcium buffer proteins are specific markers of human retinal neurons. Cell Tissue Res. 2016 Jul;365(1):29-50. doi: 10.1007/s00441-016-2376-z. Epub 2016 Feb 22. PMID: 26899253.
Kántor O, Cserpán D, Völgyi B, Lukáts Á, Somogyvári Z. The Retinal TNAP. Subcell Biochem. 2015;76:107-23. doi: 10.1007/978-94-017-7197-9_6. PMID: 26219709.
Kántor O, Benkő Z, Énzsöly A, Dávid C, Naumann A, Nitschke R, Szabó A, Pálfi E, Orbán J, Nyitrai M, Németh J, Szél Á, Lukáts Á, Völgyi B. Characterization of connexin36 gap junctions in the human outer retina. Brain Struct Funct. 2016 Jul;221(6):2963-84. doi: 10.1007/s00429-015-1082-z. Epub 2015 Jul 15. PMID: 26173976.
Debertin G, Kántor O, Kovács-Öller T, Balogh L, Szabó-Meleg E, Orbán J, Nyitrai M, Völgyi B. Tyrosine hydroxylase positive perisomatic rings are formed around various amacrine cell types in the mammalian retina. J Neurochem. 2015 Aug;134(3):416-28. doi: 10.1111/jnc.13144. Epub 2015 Jun 3. PMID: 25940543.
Kántor O, Varga A, Tóth R, Énzsöly A, Pálfi E, Kovács-Öller T, Nitschke R, Szél Á, Székely A, Völgyi B, Négyessy L, Somogyvári Z, Lukáts Á. Stratified organization and disorganization of inner plexiform layer revealed by TNAP activity in healthy and diabetic rat retina. Cell Tissue Res. 2015 Feb;359(2):409-421. doi: 10.1007/s00441-014-2047-x. Epub 2014 Nov 20. PMID: 25411053.
Kovács-Öller T, Raics K, Orbán J, Nyitrai M, Völgyi B. Developmental changes in the expression level of connexin36 in the rat retina. Cell Tissue Res. 2014 Nov;358(2):289-302. doi: 10.1007/s00441-014-1967-9. Epub 2014 Aug 12. PMID: 25110193.
Akopian A, Atlasz T, Pan F, Wong S, Zhang Y, Völgyi B, Paul DL, Bloomfield SA. Gap junction-mediated death of retinal neurons is connexin and insult specific: a potential target for neuroprotection. J Neurosci. 2014 Aug 6;34(32):10582-91. doi: 10.1523/JNEUROSCI.1912-14.2014. PMID: 25100592; PMCID: PMC4200109.
Kántor O, Varga A, Kovács-Öller T, Énzsöly A, Balogh L, Baksa G, Szepessy Z, Fonta C, Roe AW, Nitschke R, Szél Á, Négyessy L, Völgyi B, Lukáts Á. TNAP activity is localized at critical sites of retinal neurotransmission across various vertebrate species. Cell Tissue Res. 2014 Oct;358(1):85-98. doi: 10.1007/s00441-014-1944-3. Epub 2014 Jul 3. PMID: 24988913.
Völgyi B, Pan F, Paul DL, Wang JT, Huberman AD, Bloomfield SA. Gap junctions are essential for generating the correlated spike activity of neighboring retinal ganglion cells. PLoS One. 2013 Jul 23;8(7):e69426. doi: 10.1371/journal.pone.0069426. PMID: 23936012; PMCID: PMC3720567.
Retinal signalization team:
Denes V, Lukats A, Szarka G, Subicz R, Mester A, Kovacs-Valasek A, Geck P, Berta G, Herczeg R, Postyeni E, Gyenesei A, Gabriel R. Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation. Neurochem Res. 2023 Nov;48(11):3430-3446. doi: 10.1007/s11064-023-03989-7. Epub 2023 Jul 19. PMID: 37466802; PMCID: PMC10514177.
Kovács-Valasek A, Rák T, Pöstyéni E, Csutak A, Gábriel R. Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them. Int J Mol Sci. 2023 May 13;24(10):8728. doi: 10.3390/ijms24108728. PMID: 37240082; PMCID: PMC10218427.
Urbán P, Pöstyéni E, Czuni L, Herczeg R, Fekete C, Gábriel R, Kovács-Valasek A. miRNA Profiling of Developing Rat Retina in the First Three Postnatal Weeks. Cell Mol Neurobiol. 2023 Aug;43(6):2963-2974. doi: 10.1007/s10571-023-01347-3. Epub 2023 Apr 21. PMID: 37084144; PMCID: PMC10333372.
Pöstyéni E, Ganczer A, Kovács-Valasek A, Gabriel R. Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice. Front Pharmacol. 2022 Jan 13;12:808315. doi: 10.3389/fphar.2021.808315. PMID: 35095518; PMCID: PMC8793341.
Pöstyéni E, Szabadfi K, Sétáló G Jr, Gabriel R. A Promising Combination: PACAP and PARP Inhibitor Have Therapeutic Potential in Models of Diabetic and Hypertensive Retinopathies. Cells. 2021 Dec 9;10(12):3470. doi: 10.3390/cells10123470. PMID: 34943979; PMCID: PMC8700737.
Kovács-Valasek A, Pöstyéni E, Dénes V, Mester A, Sétáló G Jr, Gábriel R. Age- Related Alterations of Proteins in Albino Wistar Rat Retina. Cells Tissues Organs. 2021;210(2):135-150. doi: 10.1159/000515447. Epub 2021 Jul 2. PMID: 34218223; PMCID: PMC8315679.
Pöstyéni E, Kovács-Valasek A, Urbán P, Czuni L, Sétáló G Jr, Fekete C, Gabriel R. Profile of miR-23 Expression and Possible Role in Regulation of Glutamic Acid Decarboxylase during Postnatal Retinal Development. Int J Mol Sci. 2021 Jun 30;22(13):7078. doi: 10.3390/ijms22137078. PMID: 34209226; PMCID: PMC8268301.
Pöstyéni E, Kovács-Valasek A, Urbán P, Czuni L, Sétáló G Jr, Fekete C, Gabriel R. Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development. Int J Mol Sci. 2021 Mar 4;22(5):2577. doi: 10.3390/ijms22052577. PMID: 33806574; PMCID: PMC7961372.
Pöstyéni E, Kovács-Valasek A, Dénes V, Mester A, Sétáló G Jr, Gábriel R. PACAP for Retinal Health: Model for Cellular Aging and Rescue. Int J Mol Sci. 2021 Jan 5;22(1):444. doi: 10.3390/ijms22010444. PMID: 33466261; PMCID: PMC7796228.
Gábriel R, Pöstyéni E, Dénes V. Neuroprotective Potential of Pituitary Adenylate Cyclase Activating Polypeptide in Retinal Degenerations of Metabolic Origin. Front Neurosci. 2019;13:1031. Published 2019 Oct 9. doi:10.3389/fnins.2019.01031
Kovacs K, Vaczy A, Fekete K, Kovari P, Atlasz T, Reglodi D, Gabriel R, Gallyas F, Sumegi B. PARP Inhibitor Protects Against Chronic Hypoxia/Reoxygenation-Induced Retinal Injury by Regulation of MAPKs, HIF1α, Nrf2, and NFκB. Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1478-1490. doi: 10.1167/iovs.18-25936. PMID: 30973576.
Kovács-Valasek A, Szalontai B, Sétáló G Jr, Gábriel R. Sensitive fluorescent hybridisation protocol development for simultaneous detection of microRNA and cellular marker proteins (in the retina). Histochem Cell Biol. 2018 Nov;150(5):557-566. doi: 10.1007/s00418-018-1705-6. Epub 2018 Aug 7. PMID: 30088096; PMCID: PMC6182695.
Kovács-Valasek A, Szabadfi K, Dénes V, Szalontai B, Tamás A, Kiss P, Szabó A, Setalo G Jr, Reglődi D, Gábriel R. Accelerated retinal aging in PACAP knock-out mice. Neuroscience. 2017 Apr 21;348:1-10. doi: 10.1016/j.neuroscience.2017.02.003. Epub 2017 Feb 13. PMID: 28215987.
Lakk M, Denes V, Kovacs K, Hideg O, Szabo BF, Gabriel R. Pituitary Adenylate Cyclase-Activating Peptide (PACAP), a Novel Secretagogue, Regulates Secreted Morphogens in Newborn Rat Retina. Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):565-572. doi: 10.1167/iovs.16-20566. PMID: 28125843.
Hajna Z, Szabadfi K, Balla Z, Biró Z, Degrell P, Molnár GA, Kőszegi T, Tékus V, Helyes Z, Dobos A, Farkas S, Szűcs G, Gábriel R, Pintér E. Modeling long-term diabetes and related complications in rats. J Pharmacol Toxicol Methods. 2016 Mar-Apr;78:1-12. doi: 10.1016/j.vascn.2015.11.003. Epub 2015 Nov 14. PMID: 26589430.
Szabadfi K, Estrada C, Fernandez-Villalba E, Tarragon E, Setalo G Jr, Izura V, Reglodi D, Tamas A, Gabriel R, Herrero MT. Retinal aging in the diurnal Chilean rodent (Octodon degus): histological, ultrastructural and neurochemical alterations of the vertical information processing pathway. Front Cell Neurosci. 2015 Apr 21;9:126. doi: 10.3389/fncel.2015.00126. PMID: 25954153; PMCID: PMC4405622.
Yi F, Catudio-Garrett E, Gábriel R, Wilhelm M, Erdelyi F, Szabo G, Deisseroth K, Lawrence J. Hippocampal "cholinergic interneurons" visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation. Front Synaptic Neurosci. 2015 Mar 6;7:4. doi: 10.3389/fnsyn.2015.00004. PMID: 25798106; PMCID: PMC4351620.
Dr. Róbert Gábriel: NKFIH119289, National Brain Project KTIA_NAP_13-A-I/12;
Dr. Völgyi Béla: OTKA K105247; National Excellence Program, Szent-Györgyi Albert Senior Researcher Fellowship TÁMOP-4.2.4.A/ 2-11/1-2012-0001; National Brain Project KTIA_NAP_13-2-2015-0008.
Kovács-Öller Tamás: Pécsi Tudományegyetem Tehetségcentruma Fiatal Kiválósága (2019); Szentágothai János Tehetségtámogató Program (2019-2022); PTE, Simonyi Innovációs Díj: CellZeus (2015); Apáczai Csere János Doktoranduszi Ösztöndíj (2013-2014, TÁMOP-4.2.4.A/ 2-11/1-2012-0001); IBRO, In Europe Short Stay Grant: Roska Botond labor, FMI, Basel, Svájc (2013 feb.)
