TY - JOUR AU - Szabó, Klaudia AU - Dékány, Bulcsú AU - Énzsöly, Anna AU - Hajdú, Rozina Ida AU - Laurik-Feuerstein, Lenke Kornélia AU - Szabó, Arnold AU - Radovits, Tamás AU - Mátyás, Csaba AU - Oláh, Attila AU - Kovács, Krisztián András AU - Szél, Ágoston AU - Somfai, Gábor Márk AU - Lukáts, Ákos TI - Possible retinotoxicity of long-term vardenafil treatment JF - EXPERIMENTAL EYE RESEARCH J2 - EXP EYE RES VL - 243 PY - 2024 PG - 15 SN - 0014-4835 DO - 10.1016/j.exer.2024.109890 UR - https://m2.mtmt.hu/api/publication/34814042 ID - 34814042 LA - English DB - MTMT ER - TY - JOUR AU - Denes, Viktoria AU - Lukáts, Ákos AU - Szarka, Gergely AU - Subicz, Rovena AU - Mester, Adrienn AU - Kovács-Valasek, Andrea AU - Geck, Peter AU - Berta, Gergely AU - Herczeg, Robert AU - Pöstyéni, Etelka AU - Gyenesei, Attila AU - Gábriel, Róbert TI - Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina : Microglial Activation and Induction of Neural Proliferation JF - NEUROCHEMICAL RESEARCH J2 - NEUROCHEM RES VL - 48 PY - 2023 IS - 11 SP - 3430 EP - 3446 PG - 17 SN - 0364-3190 DO - 10.1007/s11064-023-03989-7 UR - https://m2.mtmt.hu/api/publication/34074641 ID - 34074641 N1 - Export Date: 3 April 2024 CODEN: NERED AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Dénes, Viktória AU - Kovacs, Kármen AU - Lukáts, Ákos AU - Mester, Adrienn AU - Berta, Gergely AU - Szabó, Arnold AU - Gábriel, Róbert TI - Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina. JF - EUROPEAN JOURNAL OF HISTOCHEMISTRY J2 - EUR J HISTOCHEM VL - 66 PY - 2022 IS - 2 PG - 9 SN - 1121-760X DO - 10.4081/ejh.2022.3373 UR - https://m2.mtmt.hu/api/publication/32800050 ID - 32800050 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Énzsöly, Anna AU - Hajdú, Rozina Ida AU - Turóczi, Zsolt AU - Szalai, Irén AU - Tátrai, Erika AU - Pálya, Fanni AU - Nagy, Zoltán Zsolt AU - Mátyás, Csaba AU - Oláh, Attila AU - Radovits, Tamás AU - Szabó, Klaudia AU - Dékány, Bulcsú AU - Szabó, Arnold AU - Kusnyerik, Ákos AU - Soltész, Petra AU - Veres, Dániel AU - Somogyi, Anikó AU - Somfai, Gábor Márk AU - Lukáts, Ákos TI - The Predictive Role of Thyroid Hormone Levels for Early Diabetic Retinal Changes in Experimental Rat and Human Diabetes JF - INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE J2 - INVEST OPHTH VIS SCI VL - 62 PY - 2021 IS - 6 PG - 14 SN - 0146-0404 DO - 10.1167/iovs.62.6.20 UR - https://m2.mtmt.hu/api/publication/32069056 ID - 32069056 N1 - Department of Ophthalmology, Semmelweis University, Budapest, Hungary Department of Anatomy Histology and Embryology, Semmelweis University, Budapest, Hungary 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary Heart and Vascular Center, Semmelweis University, Budapest, Hungary Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary Eye Clinic, Stadtspital Waid and Triemli, Zurich, Switzerland Werner H. Spross Foundation for the Advancement of Research and Teaching in Ophthalmology, Zurich, Switzerland Cited By :3 Export Date: 9 April 2024 CODEN: IOVSD Correspondence Address: Enzsoly, A.; Department of Ophthalmology, Ulloi ut 26, Hungary; email: anna.enzsoly@gmail.com Correspondence Address: Lukats, A.; Department of Ophthalmology, Ulloi ut 26, Hungary; email: lukatsakos@gmail.com Chemicals/CAS: liothyronine, 6138-47-2, 6893-02-3; ranibizumab, 347396-82-1; streptozocin, 18883-66-4; thyroxine, 7488-70-2; glycosylated hemoglobin, 9062-63-9; Blood Glucose; Cone Opsins; Glycated Hemoglobin A; hemoglobin A1c protein, human; Thyroid Hormones AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Hajdú, Rozina Ida AU - Laurik, Kornélia Lenke AU - Szabó, Klaudia AU - Dékány, Bulcsú AU - Kornai, Zsuzsanna AU - Énzsöly, Anna AU - Szabó, Arnold AU - Radovits, Tamás AU - Mátyás, Csaba AU - Oláh, Attila AU - Szél, Ágoston AU - Somfai, Gábor Márk AU - Dávid, Csaba AU - Lukáts, Ákos TI - Detailed Evaluation of Possible Ganglion Cell Loss in the Retina of Zucker Diabetic Fatty (ZDF) Rats JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 IS - 1 PG - 16 SN - 2045-2322 DO - 10.1038/s41598-019-46879-1 UR - https://m2.mtmt.hu/api/publication/30746871 ID - 30746871 N1 - * Megosztott szerzőség AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Jüttner, Josephine AU - Szabó, Arnold AU - Gross-Scherf, Brigitte AU - Morikawa, Rei K AU - Rompani, Santiago B AU - Hantz, Péter AU - Szikra, Tamas AU - Esposti, Federico AU - Cowan, Cameron S AU - Bharioke, Arjun AU - Patino-Alvarez, Claudia P AU - Keles, Özkan AU - Kusnyerik, Ákos AU - Azoulay, Thierry AU - Hartl, Dominik AU - Krebs, Arnaud R AU - Schübeler, Dirk AU - Hajdú, Rozina Ida AU - Lukáts, Ákos AU - Németh, János Tibor AU - Nagy, Zoltán Zsolt AU - Wu, Kun-Chao AU - Wu, Rong-Han AU - Xiang, Lue AU - Fang, Xiao-Long AU - Jin, Zi-Bing AU - Goldblum, David AU - Hasler, Pascal W AU - Scholl, Hendrik P N AU - Krol, Jacek AU - Roska, Botond TI - Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans JF - NATURE NEUROSCIENCE J2 - NAT NEUROSCI VL - 22 PY - 2019 IS - 8 SP - 1345 EP - 1356 PG - 12 SN - 1097-6256 DO - 10.1038/s41593-019-0431-2 UR - https://m2.mtmt.hu/api/publication/30736418 ID - 30736418 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Budai, András AU - Horváth, Gergő AU - Tretter, László AU - Radák, Zsolt AU - Koltai, Erika AU - Bori, Zoltán AU - Torma, Ferenc Gergely AU - Lukáts, Ákos AU - Röhlich, Pál AU - Szijártó, Attila AU - Fülöp, András TI - Mitochondrial function after associating liver partition and portal vein ligation for staged hepatectomy in an experimental model JF - BRITISH JOURNAL OF SURGERY J2 - BRIT J SURG VL - 106 PY - 2019 IS - 1 SP - 120 EP - 131 PG - 12 SN - 0007-1323 DO - 10.1002/bjs.10978 UR - https://m2.mtmt.hu/api/publication/3426954 ID - 3426954 LA - English DB - MTMT ER - TY - JOUR AU - Hammoum, Imane AU - Benlarbi, Maha AU - Dellaa, Ahmed AU - Kahloun, Rim AU - Messaoud, Riadh AU - Amara, Soumaya AU - Azaiz, Rached AU - Charfeddine, Ridha AU - Dogui, Mohamed AU - Khairallah, Moncef AU - Lukáts, Ákos AU - Ben, Chaouacha-Chekir Rafika TI - Retinal dysfunction parallels morphologic alterations and precede clinically detectable vascular alterations in Meriones shawi, a model of type 2 diabetes JF - EXPERIMENTAL EYE RESEARCH J2 - EXP EYE RES VL - 176 PY - 2018 SP - 174 EP - 187 PG - 14 SN - 0014-4835 DO - 10.1016/j.exer.2018.07.007 UR - https://m2.mtmt.hu/api/publication/30583072 ID - 30583072 N1 - Laboratory of Physiopathology, Food and Biomolecules (PAB) of the High Institute of Biotechnology, Sidi Thabet (ISBST), Univ Manouba (UMA), BiotechPole Sidi Thabet, Tunisia Faculty of Sciences of Tunis, El Manar University (UTM), Tunis, Tunisia Service of Ophtalmology, Fattouma Bourguiba University Hospital, Monastir, Tunisia UNIMED Pharmaceutical Industry, Industrial Area Kalaa Kebira, Sousse, Tunisia Service of Functional Explorations of the Nervous System, Sahloul University Hospital, Sousse, Tunisia Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary Cited By :4 Export Date: 21 November 2022 CODEN: EXERA Correspondence Address: Ben Chaouacha-Chekir, R.; Laboratory of Physiopathology, Tunisia; email: rafika.chekir@gmail.com Chemicals/CAS: glucose, 50-99-7, 84778-64-3; glutamate synthase; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; Blood Glucose AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - van der Merwe, I AU - Lukáts, Ákos AU - Blahova, V AU - Oosthuizen, MK AU - Bennett, NC AU - Nemec, P TI - 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 JF - PLOS ONE J2 - PLOS ONE VL - 13 PY - 2018 IS - 8 PG - 17 SN - 1932-6203 DO - 10.1371/journal.pone.0202106 UR - https://m2.mtmt.hu/api/publication/3408233 ID - 3408233 N1 - OA gold AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Csáki, Ágnes AU - Vereczki, Viktória AU - Lukáts, Ákos AU - Boldogkői, Zsolt AU - Sebestyén, Anna AU - Puskár, Zita AU - Köves, Katalin TI - Ontogenesis of the pinealo-retinal neuronal connection in albino rats JF - NEUROSCIENCE LETTERS J2 - NEUROSCI LETT VL - 665 PY - 2018 SP - 189 EP - 194 PG - 6 SN - 0304-3940 DO - 10.1016/j.neulet.2017.12.007 UR - https://m2.mtmt.hu/api/publication/3301703 ID - 3301703 LA - English DB - MTMT ER -