@article{MTMT:34814042, title = {Possible retinotoxicity of long-term vardenafil treatment}, url = {https://m2.mtmt.hu/api/publication/34814042}, author = {Szabó, Klaudia and Dékány, Bulcsú and Énzsöly, Anna and Hajdú, Rozina Ida and Laurik-Feuerstein, Lenke Kornélia and Szabó, Arnold and Radovits, Tamás and Mátyás, Csaba and Oláh, Attila and Kovács, Krisztián András and Szél, Ágoston and Somfai, Gábor Márk and Lukáts, Ákos}, doi = {10.1016/j.exer.2024.109890}, journal-iso = {EXP EYE RES}, journal = {EXPERIMENTAL EYE RESEARCH}, volume = {243}, unique-id = {34814042}, issn = {0014-4835}, year = {2024}, eissn = {1096-0007}, orcid-numbers = {Dékány, Bulcsú/0000-0002-2205-8567; Énzsöly, Anna/0000-0001-6557-3940; Mátyás, Csaba/0000-0001-6095-7611; Somfai, Gábor Márk/0000-0001-6329-442X} } @article{MTMT:34074641, title = {Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina : Microglial Activation and Induction of Neural Proliferation}, url = {https://m2.mtmt.hu/api/publication/34074641}, author = {Denes, Viktoria and Lukáts, Ákos and Szarka, Gergely and Subicz, Rovena and Mester, Adrienn and Kovács-Valasek, Andrea and Geck, Peter and Berta, Gergely and Herczeg, Robert and Pöstyéni, Etelka and Gyenesei, Attila and Gábriel, Róbert}, doi = {10.1007/s11064-023-03989-7}, journal-iso = {NEUROCHEM RES}, journal = {NEUROCHEMICAL RESEARCH}, volume = {48}, unique-id = {34074641}, issn = {0364-3190}, abstract = {The degenerative retinal disorders characterized by progressive cell death and exacerbating inflammation lead ultimately to blindness. The ubiquitous neuropeptide, PACAP38 is a promising therapeutic agent as its proliferative potential and suppressive effect on microglia might enable cell replacement and attenuate inflammation, respectively. Our previous finding that PACAP38 caused a marked increase of the amacrine cells in the adult (1-year-old) mouse retina, served as a rationale of the current study. We aimed to determine the proliferating elements and the inflammatory status of the PACAP38-treated retina. Three months old mice were intravitreally injected with 100 pmol PACAP38 at 3 months intervals (3X). Retinas of 1-year-old animals were dissected and effects on cell proliferation, and expression of inflammatory regulators were analyzed. Interestingly, both mitogenic and anti-mitogenic actions were detected after PACAP38-treatment. Further analysis of the mitogenic effect revealed that proliferating cells include microglia, endothelial cells, and neurons of the ganglion cell layer but not amacrine cells. Furthermore, PACAP38 stimulated retinal microglia to polarize dominantly into M2-phenotype but also might cause subsequent angiogenesis. According to our results, PACAP38 might dampen pro-inflammatory responses and help tissue repair by reprogramming microglia into an M2 phenotype, nonetheless, with angiogenesis as a warning side effect.}, keywords = {Inflammation; PROLIFERATION; ANGIOGENESIS; microglia; PACAP38; Adult retina}, year = {2023}, eissn = {1573-6903}, pages = {3430-3446}, orcid-numbers = {Gábriel, Róbert/0000-0001-9323-8795} } @article{MTMT:32800050, title = {Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina.}, url = {https://m2.mtmt.hu/api/publication/32800050}, author = {Dénes, Viktória and Kovacs, Kármen and Lukáts, Ákos and Mester, Adrienn and Berta, Gergely and Szabó, Arnold and Gábriel, Róbert}, doi = {10.4081/ejh.2022.3373}, journal-iso = {EUR J HISTOCHEM}, journal = {EUROPEAN JOURNAL OF HISTOCHEMISTRY}, volume = {66}, unique-id = {32800050}, issn = {1121-760X}, abstract = {Identified as a member of the secretin/glucagon/VIP superfamily, pituitary adenylate cyclase-activating polypeptide (PACAP1-38) has been recognized as a hormone, neurohormone, transmitter, trophic factor, and known to be involved in diverse and multiple developmental processes. PACAP1-38 was reported to regulate the production of important morphogens (Fgf1, Bmp4, Gdf3) through PAC1-receptor in the newborn rat retina. To follow up, we aimed to reveal the identity of retinal cells responsible for the production and secretion of Fgf1, Bmp4, and Gdf3 in response to PACAP1-38 treatment. Newborn (P1) rats were treated with 100 pmol PACAP1-38 intravitreally. After 24 h, retinas were dissected and processed for immunohistochemistry performed either on flat-mounted retinas or cryosections. Brn3a and PAC1-R double labeling revealed that 90% of retinal ganglion cells (RGCs) expressed PAC1-receptor. We showed that RGCs were Fgf1, Bmp4, and Gdf3-immunopositive and PAC1-R was co-expressed with each protein. To elucidate if RGCs release these secreted regulators, the key components for vesicle release were examined. No labeling was detected for synaptophysin, Exo70, or NESP55 in RGCs but an intense Rab3a-immunoreactivity was detected in their cell bodies. We found that the vast majority of RGCs are responsive to PACAP, which in turn could have a significant impact on their development or/and physiology. Although Fgf1, Bmp4, and Gdf3 were abundantly expressed in PAC1-positive RGCs, the cells lack synaptophysin and Exo70 in the newborn retina, thus unable to release these proteins. These proteins could regulate postnatal RGC development acting through intracrine pathways.}, year = {2022}, eissn = {2038-8306}, orcid-numbers = {Gábriel, Róbert/0000-0001-9323-8795} } @article{MTMT:32069056, title = {The Predictive Role of Thyroid Hormone Levels for Early Diabetic Retinal Changes in Experimental Rat and Human Diabetes}, url = {https://m2.mtmt.hu/api/publication/32069056}, author = {Énzsöly, Anna and Hajdú, Rozina Ida and Turóczi, Zsolt and Szalai, Irén and Tátrai, Erika and Pálya, Fanni and Nagy, Zoltán Zsolt and Mátyás, Csaba and Oláh, Attila and Radovits, Tamás and Szabó, Klaudia and Dékány, Bulcsú and Szabó, Arnold and Kusnyerik, Ákos and Soltész, Petra and Veres, Dániel and Somogyi, Anikó and Somfai, Gábor Márk and Lukáts, Ákos}, doi = {10.1167/iovs.62.6.20}, journal-iso = {INVEST OPHTH VIS SCI}, journal = {INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE}, volume = {62}, unique-id = {32069056}, issn = {0146-0404}, abstract = {In diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations.In rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case-control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs.A higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs.Our results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.}, year = {2021}, eissn = {1552-5783}, orcid-numbers = {Énzsöly, Anna/0000-0001-6557-3940; Szalai, Irén/0000-0001-9245-4285; Tátrai, Erika/0000-0001-7013-351X; Nagy, Zoltán Zsolt/0000-0002-7330-0464; Mátyás, Csaba/0000-0001-6095-7611; Dékány, Bulcsú/0000-0002-2205-8567; Kusnyerik, Ákos/0000-0001-9333-8104; Veres, Dániel/0000-0002-9687-3556; Somogyi, Anikó/0000-0003-0807-260X; Somfai, Gábor Márk/0000-0001-6329-442X} } @article{MTMT:30746871, title = {Detailed Evaluation of Possible Ganglion Cell Loss in the Retina of Zucker Diabetic Fatty (ZDF) Rats}, url = {https://m2.mtmt.hu/api/publication/30746871}, author = {Hajdú, Rozina Ida and Laurik, Kornélia Lenke and Szabó, Klaudia and Dékány, Bulcsú and Kornai, Zsuzsanna and Énzsöly, Anna and Szabó, Arnold and Radovits, Tamás and Mátyás, Csaba and Oláh, Attila and Szél, Ágoston and Somfai, Gábor Márk and Dávid, Csaba and Lukáts, Ákos}, doi = {10.1038/s41598-019-46879-1}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {9}, unique-id = {30746871}, issn = {2045-2322}, abstract = {A thinning of the inner retina is one of the earliest potential markers of neuroretinal damage in diabetic subjects. The histological background is uncertain; retinal ganglion cell (RGC) loss and changes in the structure or thickness of the inner plexiform layer (IPL) have been suspected. Studies conducted on animal models on RGC pathology gave contradictory results. Hereby we present RGC numbers, distribution patterns and IPL thickness from Zucker Diabetic Fatty (ZDF) rats. After labelling RGCs on retinal whole mounts, isodensity maps were constructed, RGC numbers and distribution patterns analysed using a custom-built algorithm, enabling point-by-point comparison. There was no change in staining characteristics of the antibodies and no significant difference in average RGC densities was found compared to controls. The distribution patterns were also comparable and no significant difference was found in IPL thickness and stratification or in the number of apoptotic cells in the ganglion cell layer (GCL). Our results provide a detailed evaluation of the inner retina and exclude major RGC loss in ZDF rats and suggest that other factors could serve as a potential explanation for inner retinal thinning in clinical studies. Our custom-built method could be adopted for the assessment of other animal or human retinas.}, year = {2019}, eissn = {2045-2322}, orcid-numbers = {Laurik, Kornélia Lenke/0000-0002-8713-9640; Dékány, Bulcsú/0000-0002-2205-8567; Énzsöly, Anna/0000-0001-6557-3940; Mátyás, Csaba/0000-0001-6095-7611; Somfai, Gábor Márk/0000-0001-6329-442X} } @article{MTMT:30736418, title = {Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans}, url = {https://m2.mtmt.hu/api/publication/30736418}, author = {Jüttner, Josephine and Szabó, Arnold and Gross-Scherf, Brigitte and Morikawa, Rei K and Rompani, Santiago B and Hantz, Péter and Szikra, Tamas and Esposti, Federico and Cowan, Cameron S and Bharioke, Arjun and Patino-Alvarez, Claudia P and Keles, Özkan and Kusnyerik, Ákos and Azoulay, Thierry and Hartl, Dominik and Krebs, Arnaud R and Schübeler, Dirk and Hajdú, Rozina Ida and Lukáts, Ákos and Németh, János Tibor and Nagy, Zoltán Zsolt and Wu, Kun-Chao and Wu, Rong-Han and Xiang, Lue and Fang, Xiao-Long and Jin, Zi-Bing and Goldblum, David and Hasler, Pascal W and Scholl, Hendrik P N and Krol, Jacek and Roska, Botond}, doi = {10.1038/s41593-019-0431-2}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {22}, unique-id = {30736418}, issn = {1097-6256}, abstract = {Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.}, year = {2019}, eissn = {1546-1726}, pages = {1345-1356}, orcid-numbers = {Kusnyerik, Ákos/0000-0001-9333-8104; Németh, János Tibor/0000-0001-8575-4888; Nagy, Zoltán Zsolt/0000-0002-7330-0464} } @article{MTMT:3426954, title = {Mitochondrial function after associating liver partition and portal vein ligation for staged hepatectomy in an experimental model}, url = {https://m2.mtmt.hu/api/publication/3426954}, author = {Budai, András and Horváth, Gergő and Tretter, László and Radák, Zsolt and Koltai, Erika and Bori, Zoltán and Torma, Ferenc Gergely and Lukáts, Ákos and Röhlich, Pál and Szijártó, Attila and Fülöp, András}, doi = {10.1002/bjs.10978}, journal-iso = {BRIT J SURG}, journal = {BRITISH JOURNAL OF SURGERY}, volume = {106}, unique-id = {3426954}, issn = {0007-1323}, year = {2019}, eissn = {1365-2168}, pages = {120-131}, orcid-numbers = {Budai, András/0000-0002-4634-2140; Horváth, Gergő/0000-0001-5386-9509; Tretter, László/0000-0001-5638-2886; Radák, Zsolt/0000-0003-1297-6804; Koltai, Erika/0000-0002-1370-2955; Bori, Zoltán/0000-0003-1253-060X} } @article{MTMT:30583072, title = {Retinal dysfunction parallels morphologic alterations and precede clinically detectable vascular alterations in Meriones shawi, a model of type 2 diabetes}, url = {https://m2.mtmt.hu/api/publication/30583072}, author = {Hammoum, Imane and Benlarbi, Maha and Dellaa, Ahmed and Kahloun, Rim and Messaoud, Riadh and Amara, Soumaya and Azaiz, Rached and Charfeddine, Ridha and Dogui, Mohamed and Khairallah, Moncef and Lukáts, Ákos and Ben, Chaouacha-Chekir Rafika}, doi = {10.1016/j.exer.2018.07.007}, journal-iso = {EXP EYE RES}, journal = {EXPERIMENTAL EYE RESEARCH}, volume = {176}, unique-id = {30583072}, issn = {0014-4835}, abstract = {Diabetic retinopathy is a major cause of reduced visual acuity and acquired blindness. The aim of this work was to analyze functional and vascular changes in diabetic Meriones shawi (M.sh) an animal model of metabolic syndrome and type 2 diabetes. The animals were divided into four groups. Two groups were fed a high fat diet (HFD) for 3 and 7 months, two other groups served as age-matched controls. Retinal function was assessed using full field electroretinogram (Ff-ERG). Retinal thickness and vasculature were examined by optical coherence tomography, eye fundus and fluorescein angiography. Immunohistochemistry was used to examine key proteins of glutamate metabolism and synaptic transmission. Diabetic animals exhibited significantly delayed scotopic and photopic ERG responses and decreases in scotopic and photopic a- and b-wave amplitudes at both time points. Furthermore, a decrease of the amplitude of the flicker response and variable changes in the scotopic and photopic oscillatory potentials was reported. A significant decrease in retinal thickness was observed. No evident change in the visual streak area and no sign of vascular abnormality was present; however, some exudates in the periphery were visible in 7 months diabetic animals. Imunohistochemistry detected a decrease in the expression of glutamate synthetase, vesicular glutamate transporter 1 and synaptophysin proteins. Results indicate that a significant retinal dysfunction was present in the HFD induced diabetes involving both rod and cone pathways and this dysfunction correlate well with the morphological abnormalities reported previously. Furthermore, neurodegeneration and abnormalities in retinal function occur before vascular alterations would be detectable in diabetic M.sh.}, keywords = {neurodegenerative diseases; MOUSE MODEL; GLUTAMINE-SYNTHETASE; retinopathy; optical coherence tomography; RAT RETINA; Type 2 diabetes; OSCILLATORY POTENTIALS; OCT; b-wave; Ff-ERG; ISCEV; Meriones shawi; SAND RAT}, year = {2018}, eissn = {1096-0007}, pages = {174-187}, orcid-numbers = {Dellaa, Ahmed/0000-0002-3685-7474} } @article{MTMT:3408233, title = {The topography of rods, cones and intrinsically photosensitive retinal ganglion cells in the retinas of a nocturnal (Micaelamys namaquensis) and a diurnal (Rhabdomys pumilio) rodent}, url = {https://m2.mtmt.hu/api/publication/3408233}, author = {van der Merwe, I and Lukáts, Ákos and Blahova, V and Oosthuizen, MK and Bennett, NC and Nemec, P}, doi = {10.1371/journal.pone.0202106}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {13}, unique-id = {3408233}, issn = {1932-6203}, abstract = {We used immunocytochemistry to determine the presence and topographical density distributions of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in the four-striped field mouse (Rhabdomys pumilio) and the Namaqua rock mouse (Micaelamys namaquensis). Both species possessed duplex retinas that were rod dominated. In R. pumilio, the density of both cones and rods were high (cone to rod ratio: 1:1.23) and reflected the species' fundamentally diurnal, but largely crepuscular lifestyle. Similarly, the ratio of cones to rods in M. namaquensis (1:12.4) reflected its nocturnal lifestyle. Similar rod density peaks were observed (R. pumilio: similar to 84467/mm(2); M. namaquensis: similar to 81088/mm(2)), but a density gradient yielded higher values in the central (similar to 56618/mm(2)) rather than in the peripheral retinal region (similar to 32689/mm(2)) in R. pumilio. Two separate cone types (S-cones and M/L-cones) were identified implying dichromatic color vision in the study species. In M. namaquensis, both cone populations showed a centro-peripheral density gradient and a consistent S- to M/L-cone ratio (similar to 1:7.8). In R. pumilio, S cones showed a centro-peripheral gradient (S- to M/L-cone ratio; central: 1:7.8; peripheral: 1:6.8) which appeared to form a visual streak, and a specialized area of M/L-cones (S- to M/L-cone ratio: 1:15) was observed inferior to the optic nerve. The number of photoreceptors per linear degree of visual angle, estimated from peak photoreceptor densities and eye size, were four cones and 15 rods per degree in M. namaquensis and 11 cones and 12 rods per degree in R. pumilio. Thus, in nocturnal M. namaquensis rods provide much finer image sampling than cones, whereas in diurnal/crepuscular R. pumilio both photoreceptor types provide fine image sampling. IpRGCs were comparably sparse in R. pumilio (total = 1012) and M. namaquensis (total = 862), but were homogeneously distributed in M. namaquensis and densest in the dorso-nasal quadrant in R. pumilio. The adaptive significance of the latter needs further investigation.}, keywords = {LOCOMOTOR-ACTIVITY; VISION; MAMMALIAN RETINA; light; ARCHITECTURE; Eye; MOUSE RETINA; OCULAR PHOTORECEPTORS; PHOTOENTRAINMENT; RATS RODENTIA}, year = {2018}, eissn = {1932-6203} } @article{MTMT:3301703, title = {Ontogenesis of the pinealo-retinal neuronal connection in albino rats}, url = {https://m2.mtmt.hu/api/publication/3301703}, author = {Csáki, Ágnes and Vereczki, Viktória and Lukáts, Ákos and Boldogkői, Zsolt and Sebestyén, Anna and Puskár, Zita and Köves, Katalin}, doi = {10.1016/j.neulet.2017.12.007}, journal-iso = {NEUROSCI LETT}, journal = {NEUROSCIENCE LETTERS}, volume = {665}, unique-id = {3301703}, issn = {0304-3940}, year = {2018}, eissn = {1872-7972}, pages = {189-194}, orcid-numbers = {Boldogkői, Zsolt/0000-0003-1184-7293; Sebestyén, Anna/0000-0001-8814-4794} }