{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:04:03Z","timestamp":1787241843817,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012550","name":"National Research, Development and Innovation Fund","doi-asserted-by":"publisher","award":["K135457"],"award-info":[{"award-number":["K135457"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012550","name":"National Research, Development and Innovation Fund","doi-asserted-by":"publisher","award":["NAP3.HUN-REN TKI14016"],"award-info":[{"award-number":["NAP3.HUN-REN TKI14016"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012550","name":"National Research, Development and Innovation Fund","doi-asserted-by":"publisher","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Brain Research Program","award":["K135457"],"award-info":[{"award-number":["K135457"]}]},{"name":"National Brain Research Program","award":["NAP3.HUN-REN TKI14016"],"award-info":[{"award-number":["NAP3.HUN-REN TKI14016"]}]},{"name":"National Brain Research Program","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"Stipendium Hungaricum and China Scholarship Council","award":["K135457"],"award-info":[{"award-number":["K135457"]}]},{"name":"Stipendium Hungaricum and China Scholarship Council","award":["NAP3.HUN-REN TKI14016"],"award-info":[{"award-number":["NAP3.HUN-REN TKI14016"]}]},{"name":"Stipendium Hungaricum and China Scholarship Council","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The continuously growing diabetes population is a significant concern with type 2 diabetic retinal disease (T2DRD), which is a leading cause of permanent blindness. However, the underlying pathophysiological mechanism of T2DRD has not yet been fully understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from the ovine hypothalamus based on its stimulating effect on the adenylate cyclase enzyme in anterior pituitary cells. PACAP38 (PACAP with 38 amino acids) activates anti-apoptotic pathways, inhibits pro-apoptotic signaling, and creates an anti-inflammatory environment in the retina. The aim of the present study was to test the possible retinoprotective effect of the topical administration of PACAP38 in a type 2 diabetic animal model induced by a high-fat diet and the intraperitoneally injected low-dose streptozotocin (STZ). Wistar rats were divided into four groups: the control, control + PACAP38, diabetes, and diabetes + PACAP38 groups randomly. Type 2 diabetes was induced with the combination of STZ (30 mg\/kg) and a high-fat diet. All rats were treated topically two times a day for 16 weeks: the control + PACAP38 and diabetes + PACAP38 groups were applied with PACAP38 eye drops (1 \u00b5g\/drop), while the control and diabetes groups were administered using vehicles (artificial tears). The diabetes model was validated by a fasting oral glucose tolerance test (OGTT) and C-peptide ELISA test. Animals were monitored during the whole experiment for the progression of the disease using electroretinography (ERG) and optical coherence tomography (OCT). Post-mortem immunohistochemistry and a vessel analysis were performed in the retina samples after 16 weeks. An OGTT, a C-peptide ELISA test, and the investigation of blood parameters proved the development of type 2 diabetes. Significant differences could be detected in visual function between the two diabetic groups at week 16 (in the a-wave, b-wave, and OP amplitudes), where the diabetes PACAP38-treated group was similar to the control ones. OCT measurements correlated with ERG data, where the total retinal thickness was preserved in the diabetes + PACAP38 group. PACAP38 also protected the microvascular structure in the retina. Topically administered PACAP38 has potent neuroprotective effects against type 2 diabetic retinal disease; therefore, it could be a promising therapeutic approach for the treatment of T2DRD.<\/jats:p>","DOI":"10.3390\/ijms26083753","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T08:09:17Z","timestamp":1744790957000},"page":"3753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Protective Effect of Topical PACAP38 in Retinal Morphology and Function of Type 2 Diabetic Retinopathy"],"prefix":"10.3390","volume":"26","author":[{"given":"Lina","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelin","family":"Patko","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edina","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Molitor","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0554-5904","authenticated-orcid":false,"given":"Balazs","family":"Meresz","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Reglodi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Denes","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-4257","authenticated-orcid":false,"given":"Hongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Vaczy","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-8633","authenticated-orcid":false,"given":"Tamas","family":"Atlasz","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs Medical School, Szigeti Str. 12, H-7624 Pecs, Hungary"},{"name":"Department of Sports Biology and Kinesiology, University of Pecs, Ifjusag Str. 6, H-7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","unstructured":"Atlas, I.D. (2024, September 09). Global diabetes data report 2000\u20132045. Available online: https:\/\/diabetesatlas.org\/data\/en\/world\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/BF00400947","article-title":"Presence and further development of retinal dysfunction after 3-year follow up in IDDM patients without angiographically documented vasculopathy","volume":"37","author":"Caputo","year":"1994","journal-title":"Diabetologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E2655","DOI":"10.1073\/pnas.1522014113","article-title":"Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus","volume":"113","author":"Sohn","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41746-018-0040-6","article-title":"Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices","volume":"1","author":"Lavin","year":"2018","journal-title":"npj Digit. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000444498","article-title":"Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy: Which Comes First?","volume":"56","author":"Jonsson","year":"2016","journal-title":"Ophthalmic Res."},{"key":"ref_6","first-page":"898","article-title":"Evaluation of retinal microcirculatory alterations in the goto\u2014Kakizaki rat: A spontaneous model of non-insulin-dependent diabetes","volume":"37","author":"Miyamoto","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1038\/s41374-019-0264-3","article-title":"Vascular changes in diabetic retinopathy\u2014A longitudinal study in the Nile rat","volume":"99","author":"Toh","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0002-9440(10)63626-7","article-title":"Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin\/IGF-I in diabetic autonomic neuropathy","volume":"163","author":"Schmidt","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Szab\u00f3, K., \u00c9nzs\u00f6ly, A., D\u00e9k\u00e1ny, B., Szab\u00f3, A., Hajd\u00fa, R.I., Radovits, T., M\u00e1ty\u00e1s, C., Ol\u00e1h, A., Laurik, L.K., and Somfai, G.M. (2017). Histological evaluation of diabetic neurodegeneration in the retina of Zucker Diabetic Fatty (ZDF) rats. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09068-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/ICO.0000000000001182","article-title":"Impaired corneal sensation and nerve loss in a type 2 rat model of chronic diabetes is reversible with combination therapy of menhaden oil, a-lipoic acid, and enalapril","volume":"36","author":"Davidson","year":"2017","journal-title":"Cornea"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, C., Arroba, A.I., Bogdanov, P., Ramos, H., Sim\u00f3-Servat, O., Sim\u00f3, R., and Valverde, A.M. (2020). Effect of topical administration of somatostatin on retinal inflammation and neurodegeneration in an experimental model of diabetes. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082579"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1080\/02713683.2019.1591463","article-title":"Deviation Maps for Understanding Thickness Changes of Inner Retinal Layers in Children with Type 1 Diabetes Mellitus","volume":"44","author":"Prakasam","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1097\/IAE.0000000000002576","article-title":"Changes in Total and Inner Retinal Thicknesses in Type 1 Diabetes With No Retinopathy After 8 Years of Follow-Up","volume":"40","author":"Pinilla","year":"2020","journal-title":"Retina"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/02713683.2021.2002909","article-title":"Potential of Human Neural Precursor Cells in Diabetic Retinopathy Therapeutics\u2014Preclinical Model","volume":"47","year":"2022","journal-title":"Curr. Eye Res."},{"key":"ref_15","first-page":"100","article-title":"Retinal Patterns","volume":"66","author":"Cogan","year":"1961","journal-title":"Arch. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00420981","article-title":"The development of retinopathy in sucrose-fed and streptozotocin-diabetic rats","volume":"12","author":"Papachristodoulou","year":"1976","journal-title":"Diabetologia"},{"key":"ref_17","first-page":"490","article-title":"Galactose-Induced Retinal Microangiopathy in Rats","volume":"36","author":"Kern","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e807","DOI":"10.1111\/aos.14421","article-title":"Electroretinography and retinal microvascular changes in type 2 diabetes","volume":"98","author":"Kim","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2337\/db21-0737","article-title":"Differentiating Microaneurysm Pathophysiology in Diabetic Retinopathy Through Objective Analysis of Capillary Nonperfusion, Inflammation, and Pericytes","volume":"71","author":"An","year":"2022","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/0006-291X(90)92140-U","article-title":"Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38)","volume":"170","author":"Miyata","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Horvath, G., Reglodi, D., Fabian, E., and Opper, B. (2022). Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094953"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.regpep.2006.02.009","article-title":"The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways","volume":"137","author":"Gallyas","year":"2006","journal-title":"Regul. Pept."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.2174\/1381612824666180924141407","article-title":"Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration","volume":"24","author":"Vaczy","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s12031-010-9434-x","article-title":"Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse","volume":"43","author":"Endo","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_25","first-page":"365","article-title":"Effects of Systemic PACAP Treatment in Monosodium Glutamate-Induced Behavioral Changes and Retinal","volume":"370","author":"Lubics","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6683","DOI":"10.1167\/iovs.16-20630","article-title":"Ocular delivery of PACAP1-27 protects the retina from ischemic damage in rodents","volume":"57","author":"Werling","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12031-010-9392-3","article-title":"Effects of PACAP in UV-A radiation-induced retinal degeneration models in rats","volume":"43","author":"Atlasz","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Szabo, E., Patko, E., Vaczy, A., Molitor, D., Csutak, A., Toth, G., Reglodi, D., and Atlasz, T. (2021). Retinoprotective effects of pacap eye drops in microbead-induced glaucoma model in rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168825"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s12640-015-9593-1","article-title":"Pituitary Adenylate Cyclase Activating Polypeptide, A Potential Therapeutic Agent for Diabetic Retinopathy in Rats: Focus on the Vertical Information Processing Pathway","volume":"29","author":"Szabadfi","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"P\u00f6sty\u00e9ni, E., Szabadfi, K., S\u00e9t\u00e1l\u00f3, G., and Gabriel, R. (2021). A Promising Combination: PACAP and PARP Inhibitor Have Therapeutic Potential in Models of Diabetic and Hypertensive Retinopathies. Cells, 10.","DOI":"10.3390\/cells10123470"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s12031-020-01769-4","article-title":"PACAP and NAP: Effect of Two Functionally Related Peptides in Diabetic Retinopathy","volume":"71","author":"Maugeri","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171065","DOI":"10.1016\/j.peptides.2023.171065","article-title":"PACAP-ADNP axis prevents outer retinal barrier breakdown and choroidal neovascularization by interfering with VEGF secreted from retinal pigmented epitelium cells","volume":"168","author":"Maugeri","year":"2023","journal-title":"Peptides"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10633-022-09872-0","article-title":"ISCEV Standard for full-field clinical electroretinography (2022 update)","volume":"144","author":"Robson","year":"2022","journal-title":"Doc. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1167\/iovs.17-23376","article-title":"Beyond hyperglycemia, evidence for retinal neurodegeneration in metabolic syndrome","volume":"59","author":"Karaca","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1001\/archopht.1962.00960030023005","article-title":"Electroretinogram in Diabetic Retinopathy","volume":"68","author":"Yonemura","year":"1962","journal-title":"Arch. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/eye.1989.97","article-title":"The Scotopic Threshold Response in Diabetic Retinopathy","volume":"3","author":"Aylward","year":"1989","journal-title":"Eye"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"El-Mansi, A.A., Al-Kahtani, M.A., Rady, A.M., El-Bealy, E.A., and Al-Asmari, A.M. (2021). Vitamin A and Daucus carota root extract mitigate STZ-induced diabetic retinal degeneration in Wistar albino rats by modulating neurotransmission and downregulation of apoptotic pathways. J. Food Biochem., 45.","DOI":"10.1111\/jfbc.13688"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.preteyeres.2004.06.002","article-title":"The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina","volume":"24","author":"SanGiovanni","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3341\/kjo.1993.7.2.43","article-title":"The electroretinogram sensitivity in patients with diabetes","volume":"7","author":"Chung","year":"1993","journal-title":"Korean J. Ophthalmol. KJO"},{"key":"ref_40","first-page":"2773","article-title":"A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy","volume":"33","author":"Holopigian","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1167\/iovs.09-4069","article-title":"Correlation between retinal oscillatory potentials and retinal vascular caliber in type 2 diabetes","volume":"51","author":"Luu","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0039-6257(99)00063-6","article-title":"The electroretinogram in diabetic retinopathy","volume":"44","author":"Tzekov","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0006-8993(75)90447-3","article-title":"In vivo effects of glycine on retinal ultrastructure and averaged electroretinogram","volume":"97","author":"Korol","year":"1975","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1167\/iovs.06-0845","article-title":"Reduction of oscillatory potentials and photopic negative response in patients with autosomal dominant optic atrophy with OPA1 mutations","volume":"48","author":"Miyata","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","first-page":"1153","article-title":"Integrin-Mediated Neutrophil Adhesion and Retinal Leukostasis in Diabetes","volume":"41","author":"Barouch","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","first-page":"2038","article-title":"Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: New insight on the inflammatory paradigm","volume":"28","author":"Noda","year":"2014","journal-title":"FASEB J. Res. Commun. Retin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/138161211795049679","article-title":"Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Apoptosis","volume":"17","author":"Seaborn","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00441-012-1349-0","article-title":"Protective effects of the neuropeptide PACAP in diabetic retinopathy","volume":"348","author":"Szabadfi","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neuint.2013.11.005","article-title":"PACAP promotes neuron survival in early experimental diabetic retinopathy","volume":"64","author":"Szabadfi","year":"2014","journal-title":"Neurochem. Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"G\u00e1briel, R., P\u00f6sty\u00e9ni, E., and D\u00e9nes, V. (2019). Neuroprotective Potential of Pituitary Adenylate Cyclase Activating Polypeptide in Retinal Degenerations of Metabolic Origin. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01031"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.peptides.2010.03.008","article-title":"A novel cyclopeptide from the cyclization of PACAP(1-5) with potent activity towards PAC1 attenuates STZ-induced diabetes","volume":"31","author":"Yu","year":"2010","journal-title":"Peptides"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.peptides.2017.09.014","article-title":"Modulation of IL-1\u03b2 and VEGF expression in rat diabetic retinopathy after PACAP administration","volume":"97","author":"Maugeri","year":"2017","journal-title":"Peptides"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12640-011-9254-y","article-title":"Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are more susceptible to retinal ischemic injury in vivo","volume":"21","author":"Szabadfi","year":"2012","journal-title":"Neurotox. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.2174\/1381612043383548","article-title":"Pituitary adenylate cyclase activating polypeptide: A potential neuroprotective peptide","volume":"10","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.2337\/diabetes.51.5.1453","article-title":"A potent and highly selective VPAC2 agonist enhances glucose-induced insulin release and glucose disposal: A potential therapy for type 2 diabetes","volume":"51","author":"Tsutsumi","year":"2002","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1631\/jzus.B1700254","article-title":"Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low-dose streptozotocin injection","volume":"19","author":"Guo","year":"2018","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e20180314","DOI":"10.1590\/0001-3765201920180314","article-title":"High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: A new proposal","volume":"91","author":"Kume","year":"2019","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kotb El-Sayed, M.I., Al-Massarani, S., El Gamal, A., El-Shaibany, A., and Al-Mahbashi, H.M. (2020). Mechanism of antidiabetic effects of Plicosepalus Acaciae flower in streptozotocin-induced type 2 diabetic rats, as complementary and alternative therapy. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-03087-z"},{"key":"ref_59","first-page":"e50489","article-title":"Trypsin digest protocol to analyze the retinal vasculature of a mouse model","volume":"76","author":"Chou","year":"2013","journal-title":"J. Vis. Exp."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:15:38Z","timestamp":1760030138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":59,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083753"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083753","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}