{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:16Z","timestamp":1787031436683,"version":"build-2736575974"},"reference-count":93,"publisher":"Societatea Romana de Morfologie","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rom J Morphol Embryol"],"published-print":{"date-parts":[[2025,2,20]]},"abstract":"<jats:p>Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in the pathophysiology of chronic glaucoma, as they are involved in extracellular matrix (ECM) remodeling in the trabecular meshwork (TM), affecting its ability to efficiently regulate intraocular pressure (IOP). Ensuring the balance between MMPs and TIMPs helps to maintain homeostasis in ocular tissues, which is essential to avoid glaucomatous lesions. Elevated levels of MMPs and increased degradation of the ECM, ultimately affecting aqueous humor outflow and increasing IOP, characterize glaucoma. In the current literature review, the impact and interactions of MMPs and TIMPs in chronic glaucoma have been emphasized, with multiple but still unelucidated roles in the mentioned pathology including their clinical implications, future research directions, and therapeutic approaches. Research to date indicates that the expression of TIMPs is altered in patients with chronic glaucoma, suggesting a compensatory response to increased MMPs activity. Certain drugs can influence the expression levels of MMPs and TIMPs, therefore therapeutic strategies can be developed to restore the balance between tissue enzymes and their inhibitors. Therefore, understanding the relationship between MMPs and TIMPs is a key factor in the pathogenesis of chronic glaucoma. Understanding the interplay between the two provides interesting insights into ECM remodeling in ocular tissues, highlighting the potential of targeted therapies to restore the balance between proteolytic enzymes and their inhibitors.<\/jats:p>","DOI":"10.47162\/rjme.65.4.01","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:37:15Z","timestamp":1740634635000},"page":"557-565","source":"Crossref","is-referenced-by-count":3,"title":["The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma \u2013 a literature review"],"prefix":"10.47162","volume":"65","author":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor","family":"Cerbulescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Anghel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Biochemistry, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didu\u0163a Alina","family":"Brie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Medana","family":"Petra\u015fcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Biochemistry, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u0103d\u0103lina Casiana","family":"Salavat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Ophthalmology, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina Iuliana","family":"Ardelean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Ophthalmology, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana Ramona","family":"Barac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Ophthalmology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidiu","family":"Borug\u0103","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Ophthalmology, Faculty of Medicine, Victor Babe\u015f University of Medicine and Pharmacy, Timi\u015foara, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"26736","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"\"[1] Stein JD, Khawaja AP, Weizer JS. Glaucoma in adults - screening, diagnosis, and management: a review. JAMA, 2021, 325(2):164-174. https:\/\/doi.org\/10.1001\/jama.2020.21899","DOI":"10.1001\/jama.2020.21899"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"[2] Zukerman R, Harris A, Vercellin AV, Siesky B, Pasquale LR, Ciulla TA. Molecular genetics of glaucoma: subtype and ethnicity considerations. Genes (Basel), 2020, 12(1):55. https:\/\/doi.org\/10.3390\/genes12010055","DOI":"10.3390\/genes12010055"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"[3] Sena DF, Lindsley K. Neuroprotection for treatment of glaucoma in adults. Cochrane Database Syst Rev, 2017, 1(1):CD006539. https:\/\/doi.org\/10.1002\/14651858.CD006539.pub4","DOI":"10.1002\/14651858.CD006539.pub4"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"[4] Vishwaraj CR, Kavitha S, Venkatesh R, Shukla AG, Chandran P, Tripathi S. Neuroprotection in glaucoma. Indian J Ophthalmol, 2022, 70(2):380-385. https:\/\/doi.org\/10.4103\/ijo.IJO_1158_21","DOI":"10.4103\/ijo.IJO_1158_21"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"[5] Carreon TA, Edwards G, Wang H, Bhattacharya SK. Segmental outflow of aqueous humor in mouse and human. Exp Eye Res, 2017, 158:59-66. https:\/\/doi.org\/10.1016\/j.exer.2016.08.001","DOI":"10.1016\/j.exer.2016.08.001"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"[6] Gonz\u00e1lez-Cela-Casamayor MA, L\u00f3pez-Cano JJ, Bravo-Osuna I, Andr\u00e9s-Guerrero V, Vicario-de-la-Torre M, Guzm\u00e1n-Navarro M, Ben\u00edtez-Del-Castillo JM, Herrero-Vanrell R, Molina-Mart\u00ednez IT. Novel osmoprotective DOPC-DMPC liposomes loaded with antihypertensive drugs as potential strategy for glaucoma treatment. Pharmaceutics, 2022, 14(7):1405. https:\/\/doi.org\/10.3390\/pharmaceutics14071405","DOI":"10.3390\/pharmaceutics14071405"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"[7] Xu J, Li R, Xu H, Yang Y, Zhang S, Ren TL. Recent progress of continuous intraocular pressure monitoring. Nano Select, 2021, 3(1):1-19. https:\/\/doi.org\/10.1002\/nano.202100137","DOI":"10.1002\/nano.202100137"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"[8] Verticchio Vercellin AC, Harris A, Cordell JV, Do T, Moroney J, Belamkar A, Siesky B. Mathematical modeling and glaucoma: the need for an individualized approach to risk assessment. Model Artif Intell Ophthalmol, 2016, 1(1):6-20. https:\/\/doi.org\/10.35119\/maio.v1i1.18","DOI":"10.35119\/maio.v1i1.18"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"[9] Mahmoudinezhad G, Nishida T, Weinreb RN, Baxter SL, Chang AC, Nikkhoy N, Walker E, Liebmann JM, Girkin CA, Moghimi S. Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study. BMJ Open, 2023, 13(10):e072163. https:\/\/doi.org\/10.1136\/bmjopen-2023-072163","DOI":"10.1136\/bmjopen-2023-072163"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"[10] P\u00e9rez-de-Arcelus M, Toledo E, Mart\u00ednez\u2010Gonz\u00e1lez M\u00c1, Mart\u00edn\u2010Calvo N, Fern\u00e1ndez\u2010Montero A, Moreno-Monta\u00f1\u00e9s J. Smoking and incidence of glaucoma: the SUN Cohort. Medicine (Baltimore), 2017, 96(1):e5761. https:\/\/doi.org\/10.1097\/MD.0000000000005761","DOI":"10.1097\/MD.0000000000005761"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"[11] Domngang C, Ferdinand N, Chantal N, Pamela MT, Diane K, Parick MA, Gilles K. Relation between obstructive sleep apnea-hypopnea syndrome and glaucoma in a sub-Saharan African population. Open J Ophthalmol, 2021, 11(3):191-202. https:\/\/doi.org\/10.4236\/ojoph.2021.113015","DOI":"10.4236\/ojoph.2021.113015"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"[12] Mahmoudinezhad G, Nishida T, Weinreb RN, Baxter SL, Walker E, Eslani M, Liebmann JM, Girkin CA, Moghimi S. Smoking cessation may reduce risk of visual field progression in heavy smokers. J Glaucoma, 2022, 31(10):796-803. https:\/\/doi.org\/10.1097\/IJG.0000000000002092","DOI":"10.1097\/IJG.0000000000002092"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"[13] Jayanetti V, Sandhu S, Lusthaus JA. The latest drugs in development that reduce intraocular pressure in ocular hypertension and glaucoma. J Exp Pharmacol, 2020, 12:539-548. https:\/\/doi.org\/10.2147\/JEP.S281187","DOI":"10.2147\/JEP.S281187"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"[14] Bicer GY. Clinical features of patients who were diagnosed with glaucoma incidentally. Med Sci, 2023, 12(3):618-622. https:\/\/doi.org\/10.5455\/medscience.2023.03.046","DOI":"10.5455\/medscience.2023.03.046"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"[15] Liu L. Deconstructing the mechanisms of angle closure with anterior segment optical coherence tomography. Clin Exp Ophthalmol, 2011, 39(7):614-622. https:\/\/doi.org\/10.1111\/j.1442-9071.2011.02521.x","DOI":"10.1111\/j.1442-9071.2011.02521.x"},{"issue":"42","key":"ref15","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.18410\/jebmh\/2018\/606","article-title":"A study of profile of glaucoma in a peripheral medical college in west Bengal","volume":"5","author":"Majumdar","year":"2018","unstructured":"[16] Majumdar S, Mukherjee S. A study of profile of glaucoma in a peripheral medical college in west Bengal. J Evid Based Med Healthc, 2018, 5(42):2968-2971.","journal-title":"J Evid Based Med Healthc"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"[17] Liu X, Liu X, Wang Y, Sun H, Guo Z, Tang X, Li J, Xiao X, Zheng S, Yu M, He C, Xu J, Sun W. Proteome characterization of glaucoma aqueous humor. Mol Cell Proteomics, 2021, 20:100117. https:\/\/doi.org\/10.1016\/j.mcpro.2021.100117","DOI":"10.1016\/j.mcpro.2021.100117"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"[18] Abass IA, Saleh AT, Badi AD, Mohammad BI, Hamied FM, Al-Aubaidy HA. Correlation of serum 1,25-dihydroxycholecalciferol with the incidence of primary open-angle glaucoma: a cross-sectional study on patients with chronic illnesses. Saudi J Ophthalmol, 2023, 37(3):247-249. https:\/\/doi.org\/10.4103\/sjopt.sjopt_169_22","DOI":"10.4103\/sjopt.sjopt_169_22"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"[19] Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda\u2010Jonas S. Glaucoma. Lancet, 2017, 390(10108):2183-2193. https:\/\/doi.org\/10.1016\/S0140-6736(17)31469-1","DOI":"10.1016\/S0140-6736(17)31469-1"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"[20] Chan EW, Li X, Tham YC, Liao J, Wong TY, Aung T, Cheng CY. Glaucoma in Asia: regional prevalence variations and future projections. Br J Ophthalmol, 2016, 100(1):78-85. https:\/\/doi.org\/10.1136\/bjophthalmol-2014-306102","DOI":"10.1136\/bjophthalmol-2014-306102"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"[21] Salsabila AI, Gandasubrata AP, Rifada M. Clinical characteristics and management of primary open-angle glaucoma patients at National Eye Center, Cicendo Eye Hospital, Bandung, Indonesia. J Med Health, 2023, 5(1):43-55. https:\/\/doi.org\/10.28932\/jmh.v5i1.4265","DOI":"10.28932\/jmh.v5i1.4265"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"[22] Isawumi MA, Hassan MB, Akinwusi PO, Adebimpe OW, Asekun-Olarinmoye EO, Christopher AC, Adewole TA. Awareness of and attitude towards glaucoma among an adult rural population of Osun State, Southwest Nigeria. Middle East Afr J Ophthalmol, 2014, 21(2):165-169. https:\/\/doi.org\/10.4103\/0974-9233.129769","DOI":"10.4103\/0974-9233.129769"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"[23] Zhang S, Sun J, Liu S, Liang Y, Hu Y, Congdon N, Pang CP, Wang H. Integrating opportunistic glaucoma screening into general health examinations in China: a pilot study. Clin Exp Ophthalmol, 2019, 47(8):1000-1008. https:\/\/doi.org\/10.1111\/ceo.13564","DOI":"10.1111\/ceo.13564"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"[24] Madeira MH, Ortin-Martinez A, Nadal-N\u00edcolas F, Ambr\u00f3sio AF, Vidal-Sanz M, Agudo-Barriuso M, Santiago AR. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma. Sci Rep, 2016, 6:27532. https:\/\/doi.org\/10.1038\/srep27532","DOI":"10.1038\/srep27532"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"[25] Zhao J, Wang S, Zhong W, Yang B, Sun L, Zheng Y. Oxidative stress in the trabecular meshwork (Review). Int J Mol Med, 2016, 38(4):995-1002. https:\/\/doi.org\/10.3892\/ijmm.2016.2714","DOI":"10.3892\/ijmm.2016.2714"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"[26] Kodati B, Zhang W, He S, Pham JH, Beall KJ, Swanger ZE, Krishnamoorthy VR, Harris PE, Hall T, Tran AV, Chaphalkar RM, Chavala SH, Stankowska DL, Krishnamoorthy RR. The endothelin receptor antagonist Macitentan ameliorates endothelin-mediated vasoconstriction and promotes the survival of retinal ganglion cells in rats. Front Ophthalmol (Lausanne), 2023, 3:1185755. https:\/\/doi.org\/10.3389\/fopht.2023.1185755","DOI":"10.3389\/fopht.2023.1185755"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"[27] Marola OJ, Syc-Mazurek SB, Libby RT. DDIT3 (CHOP) contributes to retinal ganglion cell somal loss but not axonal degeneration in DBA\/2J mice. Cell Death Discov, 2019, 5(1):140. https:\/\/doi.org\/10.1038\/s41420-019-0220-4","DOI":"10.1038\/s41420-019-0220-4"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"[28] Kim EK, Park HYL, Park CK. Segmented inner plexiform layer thickness as a potential biomarker to evaluate open-angle glaucoma: dendritic degeneration of retinal ganglion cell. PLoS One, 2017, 12(8):e0182404. https:\/\/doi.org\/10.1371\/journal.pone.0182404","DOI":"10.1371\/journal.pone.0182404"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"[29] Lee JH, Kwon YJ, Kim SJ, Joung B. Metabolic syndrome as an independent risk factor for glaucoma: a nationally representative study. Diabetol Metab Syndr, 2023, 15(1):177. https:\/\/doi.org\/10.1186\/s13098-023-01151-5","DOI":"10.1186\/s13098-023-01151-5"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"[30] Bosco A, Romero CO, Ambati BK, Vetter ML. In vivo dynamics of retinal microglial activation during neurodegeneration: confocal ophthalmoscopic imaging and cell morphometry in mouse glaucoma. J Vis Exp, 2015, (99):e52731. https:\/\/doi.org\/10.3791\/52731","DOI":"10.3791\/52731"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"[31] McMonnies C. Reactive oxygen species, oxidative stress, glaucoma, and hyperbaric oxygen therapy. J Optom, 2018, 11(1):3-9. https:\/\/doi.org\/10.1016\/j.optom.2017.06.002","DOI":"10.1016\/j.optom.2017.06.002"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"[32] den Haan J, Verbraak FD, Visser PJ, Bouwman FH. Retinal thickness in Alzheimer's disease: a systematic review and meta\u2010analysis. Alzheimers Dement (Amst), 2017, 6(1):162-170. https:\/\/doi.org\/10.1016\/j.dadm.2016.12.014","DOI":"10.1016\/j.dadm.2016.12.014"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"[33] Aoun P, Simpkins JW, Agarwal N. Role of PPAR-\u03b3 ligands in neuroprotection against glutamate-induced cytotoxicity in retinal ganglion cells. Glaucoma, 2003, 44(7):2999-3004. https:\/\/doi.org\/10.1167\/iovs.02-1060","DOI":"10.1167\/iovs.02-1060"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"[34] Vidal-Sanz M, Galindo-Romero C, Valiente-Soriano FJ, Nadal-Nicol\u00e1s FM, Ortin-Martinez A, Rovere G, Salinas-Navarro M, Lucas-Ruiz F, Sanchez-Migallon MC, Sobrado-Calvo P, Aviles-Trigueros M, Villegas-P\u00e9rez MP, Agudo-Barriuso M. Shared and differential retinal responses against optic nerve injury and ocular hypertension. Front Neurosci, 2017, 11:235. https:\/\/doi.org\/10.3389\/fnins.2017.00235","DOI":"10.3389\/fnins.2017.00235"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"[35] Newman-Casey PA, Shtein RM, Coleman AL, Herndon L, Lee PP. Why patients with glaucoma lose vision: the patient perspective. J Glaucoma, 2016, 25(7):e668-e675. https:\/\/doi.org\/10.1097\/IJG.0000000000000320","DOI":"10.1097\/IJG.0000000000000320"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"[36] Cauwe B, Martens E, Proost P, Opdenakker G. Multidimensional degradomics identifies systemic autoantigens and intracellular matrix proteins as novel gelatinase B\/MMP-9 substrates. Integr Biol (Camb), 2009, 1(5-6):404-426. https:\/\/doi.org\/10.1039\/b904701h","DOI":"10.1039\/b904701h"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"[37] Butler GS, Overall CM. Matrix metalloproteinase processing of signaling molecules to regulate inflammation. Periodontol 2000, 2013, 63(1):123-148. https:\/\/doi.org\/10.1111\/prd.12035","DOI":"10.1111\/prd.12035"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"[38] Cox J, Malik M, Britten J, Lewis T, Catherino WH. Ulipristal acetate and extracellular matrix production in human leiomyomas in vivo: a laboratory analysis of a randomized placebo-controlled trial. Reprod Sci, 2018, 25(2):198-206. https:\/\/doi.org\/10.1177\/1933719117728802","DOI":"10.1177\/1933719117728802"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"[39] Davey A, McAuley DF, O'Kane CM. Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair. Eur Respir J, 2011, 38(4):959-970. https:\/\/doi.org\/10.1183\/09031936.00032111","DOI":"10.1183\/09031936.00032111"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"[40] Yao M, Wang X, Zhao Y, Wang X, Gao F. Expression of MMPs is dependent on the activity of mitogen-activated protein kinase in chondrosarcoma. Mol Med Rep, 2016, 15(2):915-921. https:\/\/doi.org\/10.3892\/mmr.2016.6077","DOI":"10.3892\/mmr.2016.6077"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"[41] Sanii S, Saffar H, Tabriz HM, Qorbani M, Haghpanah V, Tavangar SM. Expression of matrix metalloproteinase-2, but not caspase-3, facilitates distinction between benign and malignant thyroid follicular neoplasms. Asian Pac J Cancer Prev, 2012, 13(5):2175-2178. https:\/\/doi.org\/10.7314\/apjcp.2012.13.5.2175","DOI":"10.7314\/APJCP.2012.13.5.2175"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"[42] van Haaften WT, Mortensen JH, Karsdal MA, Bay\u2010Jensen AC, Dijkstra G, Olinga P. Misbalance in type III collagen formation\/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease. Aliment Pharmacol Ther, 2017, 46(1):26-39. https:\/\/doi.org\/10.1111\/apt.14092","DOI":"10.1111\/apt.14092"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"[43] Ikeda H, Uzui H, Morishita T, Fukuoka Y, Sato T, Ishida K, Kaseno K, Arakawa K, Amaya N, Tama N, Shiomi Y, Lee JD, Tada H. Effect of postprandial hyperglycemia on coronary flow reserve in patients with impaired glucose tolerance and type 2 diabetes mellitus. Diab Vasc Dis Res, 2015, 12(6):405-410. https:\/\/doi.org\/10.1177\/1479164115597866","DOI":"10.1177\/1479164115597866"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"[44] Elkington PTG, O'Kane CM, Friedland JS. The paradox of matrix metalloproteinases in infectious disease. Clin Exp Immunol, 2005, 142(1):12-20. https:\/\/doi.org\/10.1111\/j.1365-2249.2005.02840.x","DOI":"10.1111\/j.1365-2249.2005.02840.x"},{"issue":"1","key":"ref44","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.26420\/austinjgastroenterol.2017.1074","article-title":"Metastatic Kaposi's sarcoma causing gastrointestinal bleeding: report of an unusual case","volume":"4","author":"Huang","year":"2017","unstructured":"[45] Huang MY, Liu FC, Gao HW, Huang TY. Metastatic Kaposi's sarcoma causing gastrointestinal bleeding: report of an unusual case. Austin J Gastroenterol, 2017, 4(1):1074.","journal-title":"Austin J Gastroenterol"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"[46] Helin-Toiviainen M, R\u00f6nkk\u00f6 S, Puustj\u00e4rvi T, Rekonen P, Ollikainen M, Uusitalo H. Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients. Acta Ophthalmol, 2014, 93(2):165-171. https:\/\/doi.org\/10.1111\/aos.12550","DOI":"10.1111\/aos.12550"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"[47] Kim MH, Lim SH. Matrix metalloproteinases and glaucoma. Biomolecules, 2022, 12(10):1368. https:\/\/doi.org\/10.3390\/biom12101368","DOI":"10.3390\/biom12101368"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"[48] Thakur N, Kupani M, Pandey RK, Mannan R, Pruthi A, Mehrotra S. Genetic association of -1562C>T polymorphism in the MMP9 gene with primary glaucoma in a north Indian population. PLoS One, 2018, 13(2):e0192636. https:\/\/doi.org\/10.1371\/journal.pone.0192636","DOI":"10.1371\/journal.pone.0192636"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"[49] Xu S, Liu S, Yan G. Lycium barbarum exerts protection against glaucoma-like injury via inhibition of MMP-9 signaling in vitro. Med Sci Monit, 2019, 25:9794-9800. https:\/\/doi.org\/10.12659\/MSM.919187","DOI":"10.12659\/MSM.919187"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"[50] Zaleska-\u017bmijewska A, Strzemecka E, Wawrzyniak ZW, Szaflik JP. Extracellular MMP-9-based assessment of ocular surface inflammation in patients with primary open-angle glaucoma. J Ophthalmol, 2019, 2019:1240537. https:\/\/doi.org\/10.1155\/2019\/1240537","DOI":"10.1155\/2019\/1240537"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"[51] Chen H, Zheng G, Chen H, Li L, Xu Z, Xu L. Evaluations of aqueous humor protein markers in different types of glaucoma. Medicine (Baltimore), 2022, 101(41):e31048. https:\/\/doi.org\/10.1097\/MD.0000000000031048","DOI":"10.1097\/MD.0000000000031048"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"[52] Singh D, Srivastava SK, Chaudhuri TK, Upadhyay G. Multifaceted role of matrix metalloproteinases (MMPs). Front Mol Biosci, 2015, 2:19. https:\/\/doi.org\/10.3389\/fmolb.2015.00019","DOI":"10.3389\/fmolb.2015.00019"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"[53] Costa S, Ragusa MA, Lo Buglio G, Scilabra SD, Nicosia A. The repertoire of tissue inhibitors of metalloproteases: evolution, regulation of extracellular matrix proteolysis, engineering and therapeutic challenges. Life, 2022, 12(8):1145. https:\/\/doi.org\/10.3390\/life12081145","DOI":"10.3390\/life12081145"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"[54] Warner RB, Najy AJ, Jung YS, Fridman R, Kim S, Kim HRC. Establishment of structure-function relationship of tissue inhibitor of metalloproteinase-1 for its interaction with CD63: implication for cancer therapy. Sci Rep, 2020, 10(1):2099. https:\/\/doi.org\/10.1038\/s41598-020-58964-x","DOI":"10.1038\/s41598-020-58964-x"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"[55] Batra J, Robinson J, Soares AS, Fields AP, Radisky DC, Radisky ES. Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure. J Biol Chem, 2012, 287(19):15935-15946. https:\/\/doi.org\/10.1074\/jbc.M112.341156","DOI":"10.1074\/jbc.M112.341156"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"[56] Iyer S, Wei S, Brew K, Acharya KR. Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1. J Biol Chem, 2007, 282(1):364-371. https:\/\/doi.org\/10.1074\/jbc.M607625200","DOI":"10.1074\/jbc.M607625200"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"[57] Yu WH, Yu S, Meng Q, Brew K, Woessner JF Jr. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J Biol Chem, 2000, 275(40):31226-31232. https:\/\/doi.org\/10.1074\/jbc.M000907200","DOI":"10.1074\/jbc.M000907200"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"[58] Moore CS, Crocker SJ. An alternate perspective on the roles of TIMPs and MMPs in pathology. Am J Pathol, 2012, 180(1):12-16. https:\/\/doi.org\/10.1016\/j.ajpath.2011.09.008","DOI":"10.1016\/j.ajpath.2011.09.008"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"[59] Suryapranata IGAGDP, Mulyawan IM, Mahadewa TGB. The relationship between tissue inhibitor metalloproteinase-1 with colorectal cancer and tissue inhibitor metalloproteinase-1 as a predictor of colorectal cancer. Int J Health Sci, 2022, 6(S7):6401-6411. https:\/\/doi.org\/10.53730\/ijhs.v6nS7.13617","DOI":"10.53730\/ijhs.v6nS7.13617"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"[60] Gu X, Fu M, Ding Y, Ni H, Zhang W, Zhu Y, Tang X, Xiong L, Li J, Qiu L, Xu J, Zhu J. TIMP-3 expression associates with malignant behaviors and predicts favorable survival in HCC. PLoS One, 2014, 9(8):e106161. https:\/\/doi.org\/10.1371\/journal.pone.0106161","DOI":"10.1371\/journal.pone.0106161"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"[61] Stetler-Stevenson WG, Gavil NV. Normalization of the tumor microenvironment: evidence for tissue inhibitor of metalloproteinase-2 as a cancer therapeutic. Connect Tissue Res, 2014, 55(1):13-19. https:\/\/doi.org\/10.3109\/03008207.2013.867339","DOI":"10.3109\/03008207.2013.867339"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"[62] Fan D, Takawale A, Lee J, Kassiri Z. Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenesis Tissue Repair, 2012, 5(1):15. https:\/\/doi.org\/10.1186\/1755-1536-5-15","DOI":"10.1186\/1755-1536-5-15"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"[63] Costanzo L, Soto B, Meier R, Geraghty P. The biology and function of tissue inhibitor of metalloproteinase 2 in the lungs. Pulm Med, 2022, 2022:3632764. https:\/\/doi.org\/10.1155\/2022\/3632764","DOI":"10.1155\/2022\/3632764"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"[64] Thiele ND, Wirth JW, Steins D, Koop AC, Ittrich H, Lohse AW, Kluwe J. TIMP-1 is upregulated, but not essential in hepatic fibrogenesis and carcinogenesis in mice. Sci Rep, 2017, 7(1):714. https:\/\/doi.org\/10.1038\/s41598-017-00671-1","DOI":"10.1038\/s41598-017-00671-1"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"[65] Kudaka DM, \u0141odej PK, Baier A, Szyszka R. Metalloproteinases of the extracellular matrix and their inhibitors. BioTechnologia, 2016, 97(2):129-136. https:\/\/doi.org\/10.5114\/bta.2016.60782","DOI":"10.5114\/bta.2016.60782"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"[66] Mina\u0159\u00edkov\u00e1 M, F\u00edk Z, \u0160torm J, Helisov\u00e1 K, Ferrov\u00e1 K, Mahelkov\u00e1 G. Tear matrix metalloproteinase-9 levels may help to follow an ocular surface injury in lagophthalmic eyes. PLoS One, 2022, 17(9):e0274173. https:\/\/doi.org\/10.1371\/journal.pone.0274173","DOI":"10.1371\/journal.pone.0274173"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"[67] Yeu E, Goldberg DF, Mah FS, Beckman KA, Luchs JI, Solomon JD, White DE, Gupta PK. Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease. Clin Ophthalmol, 2019, 13:887-894. https:\/\/doi.org\/10.2147\/OPTH.S203510","DOI":"10.2147\/OPTH.S203510"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"[68] Dallinga M, Murtagh P, Powell S, Murphy CC. Moraxella nonliquefaciens-associated infectious scleritis. BMJ Case Rep, 2023, 16(5):e254113. https:\/\/doi.org\/10.1136\/bcr-2022-254113","DOI":"10.1136\/bcr-2022-254113"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"[69] Singh M, Tyagi SC. Metalloproteinases as mediators of inflammation and the eyes: molecular genetic underpinnings governing ocular pathophysiology. Int J Ophthalmol, 2017, 10(8):1308-1318. https:\/\/doi.org\/10.18240\/ijo.2017.08.20","DOI":"10.18240\/ijo.2017.08.20"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"[70] Fountoulakis N, Labiris G, Aristeidou A, Katsanos A, Tentes I, Kortsaris A, Kozobolis VP. Tissue inhibitor of metalloproteinase 4 in aqueous humor of patients with primary open angle glaucoma, pseudoexfoliation syndrome, and pseudoexfoliative glaucoma and its role in proteolysis imbalance. BMC Ophthalmol, 2013, 13(1):69. https:\/\/doi.org\/10.1186\/1471-2415-13-69","DOI":"10.1186\/1471-2415-13-69"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"[71] McGrady NR, Pasini S, Baratta RO, Del Buono BJ, Schlumpf E, Calkins DJ. Restoring the extracellular matrix: a neuroprotective role for collagen mimetic peptides in experimental glaucoma. Front Pharmacol, 2021, 12:764709. https:\/\/doi.org\/10.3389\/fphar.2021.764709","DOI":"10.3389\/fphar.2021.764709"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"[72] Wu MY, Wu Y, Zhang Y, Liu CY, Deng CY, Peng L, Zhou L. Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis. BMC Ophthalmol, 2017, 17(1):48. https:\/\/doi.org\/10.1186\/s12886-017-0442-2","DOI":"10.1186\/s12886-017-0442-2"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"[73] Chen Y, Yan H, Li G, Zhang Y. Higher TGF-\u03b21, TGF-\u03b22, MMP-2, and TIMP-1 levels in the aqueous humor of patients with acute primary angle closure. Ophthalmic Res, 2020, 64(1):62-67. https:\/\/doi.org\/10.1159\/000507762","DOI":"10.1159\/000507762"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"[74] Maddineni P, Kasetti RB, Kodati B, Yacoub S, Zode GS. Sodium 4-Phenylbutyrate reduces ocular hypertension by degrading extracellular matrix deposition via activation of MMP9. Int J Mol Sci, 2021, 22(18):10095. https:\/\/doi.org\/10.3390\/ijms221810095","DOI":"10.3390\/ijms221810095"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"[75] Ponomarenko I, Reshetnikov E, Dvornyk V, Churnosov M. Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia. Eur J Ophthalmol, 2022, 32(6):3208-3219. https:\/\/doi.org\/10.1177\/11206721221083722","DOI":"10.1177\/11206721221083722"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"[76] Dammak A, Sanchez Naves J, Huete-Toral F, Carracedo G. New biomarker combination related to oxidative stress and inflammation in primary open-angle glaucoma. Life (Basel), 2023, 13(7):1455. https:\/\/doi.org\/10.3390\/life13071455","DOI":"10.3390\/life13071455"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"[77] Nguyen DD, Luo LJ, Lai JY. Dendritic effects of injectable biodegradable thermogels on pharmacotherapy of inflammatory glaucoma\u2010associated degradation of extracellular matrix. Adv Healthc Mater, 2019, 8(24):e1900702. https:\/\/doi.org\/10.1002\/adhm.201900702","DOI":"10.1002\/adhm.201900702"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"[78] Zhao F, Fan Z, Huang X. Role of matrix metalloproteinase\u20109 gene polymorphisms in glaucoma: a hospital\u2010based study in Chinese patients. J Clin Lab Anal, 2020, 34(3):e23105. https:\/\/doi.org\/10.1002\/jcla.23105","DOI":"10.1002\/jcla.23105"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"[79] Sahay P, Rao A, Padhy D, Sarangi S, Das G, Reddy MM, Modak R. Functional activity of matrix metalloproteinases 2 and 9 in tears of patients with glaucoma. Invest Ophthalmol Vis Sci, 2017, 58(6):BIO106-BIO113. https:\/\/doi.org\/10.1167\/iovs.17-21723","DOI":"10.1167\/iovs.17-21723"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"[80] Shima I, Katsuda S, Ueda Y, Takahashi N, Sasaki H. Expression of matrix metalloproteinases in wound healing after glaucoma filtration surgery in rabbits. Ophthalmic Res, 2007, 39(6):315-324. https:\/\/doi.org\/10.1159\/000109987","DOI":"10.1159\/000109987"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"[81] Gupta P, Senthil S, Srirampur A, Mittal P. Role of oral Doxycycline in the management of conjunctival dehiscence following glaucoma drainage device. Int Surg J, 2017, 4(7):2369-2371. https:\/\/doi.org\/10.18203\/2349-2902.isj20172801","DOI":"10.18203\/2349-2902.isj20172801"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"[82] Sun L, Cui R, Meng H, Liu X, Liu X, Lu Y, Liu K, Jia L, Zheng Y. Gene suppression of the chloride channel 2 suppressed TGF-\u03b21-induced proliferation, collagen synthesis, and collagen gel contraction mediated by conjunctival fibroblasts. Ophthalmic Res, 2021, 64(5):775-784. https:\/\/doi.org\/10.1159\/000507632","DOI":"10.1159\/000507632"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"[83] Kara S, Y\u0131ld\u0131r\u0131m N, \u00d6zer A, \u00c7olak \u00d6, \u015eahin A. Matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2, and transforming growth factor beta 1 in the aqueous humor and serum of patients with pseudoexfoliation syndrome. Clin Ophthalmol, 2014, 8:305-309. https:\/\/doi.org\/10.2147\/OPTH.S55914","DOI":"10.2147\/OPTH.S55914"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"[84] Rasmussen CA, Kaufman PL. The trabecular meshwork in normal eyes and in exfoliation glaucoma. J Glaucoma, 2014, 23(8 Suppl 1):S15-S19. https:\/\/doi.org\/10.1097\/IJG.0000000000000106","DOI":"10.1097\/IJG.0000000000000106"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"[85] Pluda S, Mazzocato Y, Angelini A. Peptide-based inhibitors of ADAM and ADAMTS metalloproteinases. Front Mol Biosci, 2021, 8:703715. https:\/\/doi.org\/10.3389\/fmolb.2021.703715","DOI":"10.3389\/fmolb.2021.703715"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"[86] Raeeszadeh\u2010Sarmazdeh M, Do LD, Hritz BG. Metalloproteinases and their inhibitors: potential for the development of new therapeutics. Cells, 2020, 9(5):1313. https:\/\/doi.org\/10.3390\/cells9051313","DOI":"10.3390\/cells9051313"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"[87] Arkadash V, Radisky ES, Papo N. Combinatorial engineering of N-TIMP2 variants that selectively inhibit MMP9 and MMP14 function in the cell. Oncotarget, 2018, 9(62):32036-32053. https:\/\/doi.org\/10.18632\/oncotarget.25885","DOI":"10.18632\/oncotarget.25885"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"[88] Redman M, King A, Watson C, King D. What is CRISPR\/Cas9? Arch Dis Child Educ Pract Ed, 2016, 101(4):213-215. https:\/\/doi.org\/10.1136\/archdischild-2016-310459","DOI":"10.1136\/archdischild-2016-310459"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"[89] Li X, Lin J, Ding X, Xuan J, Hu Z, Wu D, Zhu X, Feng Z, Ni W, Wu A. The protective effect of sinapic acid in osteoarthritis: in vitro and in vivo studies. J Cell Mol Med, 2019, 23(3):1940-1950. https:\/\/doi.org\/10.1111\/jcmm.14096","DOI":"10.1111\/jcmm.14096"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"[90] McMahon M, Ye S, Pedrina J, Dlugolenski D, Stambas J. Extracellular matrix enzymes and immune cell biology. Front Mol Biosci, 2021, 8:703868. https:\/\/doi.org\/10.3389\/fmolb.2021.703868","DOI":"10.3389\/fmolb.2021.703868"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"[91] Kwon MJ. Matrix metalloproteinases as therapeutic targets in breast cancer. Front Oncol, 2023, 12:1108695. https:\/\/doi.org\/10.3389\/fonc.2022.1108695","DOI":"10.3389\/fonc.2022.1108695"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"[92] Ji Y, Xiao Y, Xu L, He J, Qian C, Li W, Wu L, Chen R, Wang J, Hu R, Zhang X, Gu Z, Chen Z. Drug-bearing supramolecular MMP inhibitor nanofibers for inhibition of metastasis and growth of liver cancer. Adv Sci (Weinh), 2018, 5(8):1700867. https:\/\/doi.org\/10.1002\/advs.201700867","DOI":"10.1002\/advs.201700867"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"[93] Zipfel P, Rochais C, Baranger K, Rivera S, Dallemagne P. Matrix metalloproteinases as new targets in Alzheimer's disease: opportunities and challenges. J Med Chem, 2020, 63(19):10705-10725. https:\/\/doi.org\/10.1021\/acs.jmedchem.0c00352\"","DOI":"10.1021\/acs.jmedchem.0c00352"}],"container-title":["Romanian Journal of Morphology and Embryology"],"original-title":[],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T05:46:24Z","timestamp":1740635184000},"score":1,"resource":{"primary":{"URL":"https:\/\/rjme.ro\/archive\/65\/4\/1\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":93,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2,13]]},"published-print":{"date-parts":[[2025,2,20]]}},"URL":"https:\/\/doi.org\/10.47162\/rjme.65.4.01","relation":{},"ISSN":["1220-0522","2066-8279"],"issn-type":[{"value":"1220-0522","type":"print"},{"value":"2066-8279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}