{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:07Z","timestamp":1785426127942,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amasya University Scientific Research Project","award":["FMB-BAP: 22-0557"],"award-info":[{"award-number":["FMB-BAP: 22-0557"]}]},{"award":["FMB-BAP: 22-0557"],"award-info":[{"award-number":["FMB-BAP: 22-0557"]}],"id":[{"id":"https:\/\/ror.org\/00sbx0y13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes may impair anterior segment immune regulation. Because transforming growth factor-\u03b22 maintains ocular immune privilege, while nuclear factor-\u03baB is linked to inflammatory activation, we compared their aqueous humor levels in cataract patients with and without diabetes. Methods: In this prospective cross-sectional study, aqueous humor samples were collected from 90 patients (30 diabetic, 60 non-diabetic) via anterior chamber needle aspiration at the commencement of routine phacoemulsification, prior to viscoelastic injection, without additional intervention. Transforming growth factor-\u03b22 and nuclear factor-\u03baB levels were then measured using enzyme-linked immunosorbent assay (ELISA). Between-group comparisons and ROC curve analyses were performed to evaluate differences in biomarker levels and their discriminative ability in distinguishing diabetic status. Covariate-adjusted analysis (ANCOVA) was additionally performed. Results: Transforming growth factor-\u03b22 levels were significantly lower in the diabetic group (p &lt; 0.001), while nuclear factor-\u03baB levels showed no significant difference (p = 0.285). The between-group difference in transforming growth factor-\u03b22 remained significant after adjustment for cataract grade and hypertension duration (F(1,86) = 17.901, p &lt; 0.001, partial \u03b72 = 0.172; Cohen\u2019s d = 0.94). Transforming growth factor-\u03b22 demonstrated high specificity (100%) but limited sensitivity (45%) for identifying diabetic status at a cut-off of &lt;449.25 ng\/L; however, given the small sample size and exploratory nature of the study, this specificity value should be interpreted with caution and requires validation in larger cohorts. Conclusions: Lower aqueous humor TGF-\u03b22 levels in diabetic cataract patients, independent of cataract severity and hypertension duration, suggest that TGF-\u03b22 suppression may represent an earlier molecular event in anterior segment immune dysregulation preceding overt inflammatory activation. While TGF-\u03b22 shows exploratory biomarker potential, validation in larger, prospective, mechanistic studies is required before clinical application.<\/jats:p>","DOI":"10.3390\/jcm15124807","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:03:23Z","timestamp":1782263003000},"page":"4807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Aqueous Humor TGF-\u03b22 Levels in Diabetic Cataract: A Comparative Analysis with NF-\u03baB"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-5442","authenticated-orcid":false,"given":"Duygu Tozcu","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Amasya University, Amasya 05100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-0116","authenticated-orcid":false,"given":"Mehmet Ali","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Amasya University, Amasya 05100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-6509","authenticated-orcid":false,"given":"Mustafa","family":"Capraz","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, Faculty of Medicine, Amasya University, Amasya 05100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melek","family":"Tufek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Amasya University, Amasya 05100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihat","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Amasya University, Amasya 05100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.4239\/wjd.v10.i3.140","article-title":"Cataract in Diabetes Mellitus","volume":"10","author":"Kiziltoprak","year":"2019","journal-title":"World J. Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2337\/db20191-6","article-title":"Cataracts and Their Treatment in People with Diabetes","volume":"2019","author":"Bixler","year":"2019","journal-title":"ADA Clin. Compend."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fortenbach, C.R., Skeie, J.M., Sevcik, K.M., Johnson, A.T., Oetting, T.A., Haugsdal, J.M., Sales, C.S., Nishimura, D.Y., Taylor, E.B., and Schmidt, G.A. (2023). Metabolic and Proteomic Indications of Diabetes Progression in Human Aqueous Humor. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0280491"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dolar-Szczasny, J., Drab, A., Rejdak, R., Dolar-Szczasny, J., Drab, A., and Rejdak, R. (2024). Biochemical Changes in Anterior Chamber of the Eye in Diabetic Patients\u2014A Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13092581"},{"key":"ref_5","first-page":"1477","article-title":"Determination of Active TGF-Beta2 in Aqueous Humor Prior to and Following Cryopreservation","volume":"12","author":"Maier","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dillinger, A.E., Kuespert, S., Seleem, A.A., Neuendorf, J., Schneider, M., and Fuchshofer, R. (2023). CCN2\/CTGF Tip the Balance of Growth Factors towards TGF-\u03922 in Primary Open-Angle Glaucoma. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1045411"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared Principles in NF-kappaB Signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Suryavanshi, S.V., and Kulkarni, Y.A. (2017). NF-\u039a\u03b2: A Potential Target in the Management of Vascular Complications of Diabetes. Front Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00798"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109904","DOI":"10.1016\/j.exer.2024.109904","article-title":"Aqueous Humor as Eye Lymph: A Crossroad between Venous and Lymphatic System","volume":"243","author":"Benagiano","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2174\/1874364101004010052","article-title":"Aqueous Humor Dynamics: A Review","volume":"4","author":"Goel","year":"2010","journal-title":"Open Ophthalmol. J."},{"key":"ref_11","first-page":"830","article-title":"Comparison of Aqueous Humor Cytokine and Chemokine Levels in Diabetic Patients with and without Retinopathy","volume":"18","author":"Cheung","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.trsl.2021.05.005","article-title":"Immune Responses to Injury and Their Links to Eye Disease","volume":"236","author":"Stepp","year":"2021","journal-title":"Transl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcjd.2015.07.002","article-title":"Aqueous Humour and Serum Levels of Nitric Oxide, Malondialdehyde and Total Antioxidant Status in Patients with Type 2 Diabetes with Proliferative Diabetic Retinopathy and Nondiabetic Senile Cataracts","volume":"40","author":"Karalezli","year":"2016","journal-title":"Can. J. Diabetes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"571","DOI":"10.18240\/ijo.2023.04.11","article-title":"Comparison of Anterior Segment Parameters of the Eye between Type 2 Diabetic with and without Diabetic Retinopathy and Non-Diabetic","volume":"16","author":"Asharlous","year":"2023","journal-title":"Int. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.preteyeres.2011.05.002","article-title":"Inflammation in Diabetic Retinopathy","volume":"30","author":"Tang","year":"2011","journal-title":"Prog. Retin Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108829","DOI":"10.1016\/j.exer.2021.108829","article-title":"The Local Wound Environment Is a Key Determinant of the Outcome of TGF\u03b2 Signaling on the Fibrotic Response of CD44+ Leader Cells in an Ex Vivo Post-Cataract-Surgery Model","volume":"213","author":"Basta","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.18240\/ijo.2019.10.01","article-title":"Celastrol Inhibits Migration, Proliferation and Transforming Growth Factor-\u03922-Induced Epithelial-Mesenchymal Transition in Lens Epithelial Cells","volume":"12","author":"Wang","year":"2019","journal-title":"Int. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100402","DOI":"10.1016\/j.clinsp.2024.100402","article-title":"Changes in PEDF, MMP-2, and TGF-\u03922 Levels in the Aqueous Humor of Cataract Patients and Their Correlation with Disease Severity","volume":"79","author":"Lin","year":"2024","journal-title":"Clinics (Sao Paulo)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1159\/000083019","article-title":"Concentration of Transforming Growth Factor Beta2 in Aqueous Humor","volume":"37","author":"Yamamoto","year":"2005","journal-title":"Ophthalmic Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gao, C., Lin, X., Fan, F., Liu, X., Wan, H., Yuan, T., Zhao, X., and Luo, Y. (2022). Status of Higher TGF-\u03921 and TGF-\u03922 Levels in the Aqueous Humour of Patients with Diabetes and Cataracts. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02317-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e206","DOI":"10.1111\/aos.13230","article-title":"Aqueous Humour Concentrations of TGF-\u03b2, PLGF and FGF-1 and Total Retinal Blood Flow in Patients with Early Non-Proliferative Diabetic Retinopathy","volume":"95","author":"Khuu","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"608751","DOI":"10.1155\/2010\/608751","article-title":"Diabetic Cataract\u2014Pathogenesis, Epidemiology and Treatment","volume":"2010","author":"Pollreisz","year":"2010","journal-title":"J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jcrs.2015.09.027","article-title":"Elevated TGF-\u03922 Level in Aqueous Humor of Cataract Patients with High Myopia: Potential Risk Factor for Capsule Contraction Syndrome","volume":"42","author":"Zhu","year":"2016","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1007\/s10792-020-01463-9","article-title":"Comparison of Inflammatory Cytokines Levels in the Aqueous Humor with Diabetic Retinopathy","volume":"40","author":"Zhang","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Karakosta, C., Samiotaki, M., Bisoukis, A., Bougioukas, K.I., Panayotou, G., Papaconstantinou, D., Moschos, M.M., Karakosta, C., Samiotaki, M., and Bisoukis, A. (2025). Differential Signaling Pathways Identified in Aqueous Humor, Anterior Capsule, and Crystalline Lens of Age-Related, Diabetic, and Post-Vitrectomy Cataract. Proteomes, 13.","DOI":"10.3390\/proteomes13010007"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, Y., Cheng, T., Zhou, S., Li, F., Guo, W., Li, M., and Liu, T. (2025). Changes in Aqueous Humor Cytokines and Metabolomics in Contralateral Eye after Unilateral Cataract Surgery. BMC Ophthalmol., 25.","DOI":"10.1186\/s12886-025-03961-9"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rakib-Uz-Zaman, S.M., Werner, L., and Duncan, M.K. (2025). Unanswered Questions Regarding the Pathogenesis of Late Onset Posterior Capsular Opacification. Front Ophthalmol., 5.","DOI":"10.3389\/fopht.2025.1680042"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1091\/mbc.e16-12-0865","article-title":"Dual Function of TGF\u03b2 in Lens Epithelial Cell Fate: Implications for Secondary Cataract","volume":"28","author":"Boswell","year":"2017","journal-title":"MBoC"},{"key":"ref_29","first-page":"1520","article-title":"Regulation of Transforming Growth Factor \u0392-mediated Epithelial-mesenchymal Transition of Lens Epithelial Cells by c-Src Kinase under High Glucose Conditions","volume":"16","author":"Han","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110530","DOI":"10.1016\/j.exer.2025.110530","article-title":"NOX4 Facilitates Diabetic Cataract Progression through the NF-\u03baB Signaling Pathway","volume":"259","author":"Su","year":"2025","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s10142-023-01152-7","article-title":"Involvement of IGF1 in Endoplasmic Reticulum Stress Contributes to Cataract Formation through Regulating Nrf2\/NF-\u03baB Signaling","volume":"23","author":"Peng","year":"2023","journal-title":"Funct. Integr. Genom."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Garc\u00eda, V.A., Alameda, J.P., Page, A., and Casanova, M.L. (2021). Role of NF-\u03baB in Ageing and Age-Related Diseases: Lessons from Genetically Modified Mouse Models. Cells, 10.","DOI":"10.3390\/cells10081906"},{"key":"ref_33","first-page":"423","article-title":"The Significance of Akt\/NF-\u039ab Signaling Pathway in the Posterior Cataract Animal Model","volume":"118","author":"Shao","year":"2017","journal-title":"Bratisl. Lek. Listy"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:26:32Z","timestamp":1782264392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,21]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcm15124807"],"URL":"https:\/\/doi.org\/10.3390\/jcm15124807","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,21]]}}}