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It represents the overall deformability of the cornea, and reduces significantly with age. Low CH has also been associated with optic nerve damage and progression of visual field loss in glaucoma. The extracellular matrix (ECM) constituents of the cornea, trabecular meshwork (TM), sclera, and lamina cribrosa (LC) are similar, as they are predominantly made of fibrillar collagen. This suggests that biomechanical changes in the cornea may also reflect optic nerve compliance in glaucomatous optic neuropathy, and in the known increase of TM tissue stiffness in glaucoma. Increased collagen cross-linking contributes to tissue stiffening throughout the body, which is observed in normal aging and occurs at an accelerated rate in systemic conditions such as fibrotic and cardiovascular diseases, cancer, and glaucoma. We reviewed 3 ECM cross-linking proteins that may have a potential role in the disease process of increased tissue stiffness in glaucoma, including lysyl oxidase (LOX)\/lysyl oxidase-like 1 (LOXL1), tissue transglutaminase (TG2), and advanced glycation end products. We also report elevated messenger RNA (mRNA) levels of LOX and TG2 in glaucoma LC cells to support our proposed theory that increased levels of cross-linking proteins in glaucoma play a role in LC tissue stiffness. We highlight areas of research that are needed to better understand the role of cross-linking in glaucoma pathogenesis, leading potentially to a novel therapeutic strategy.<\/jats:p>","DOI":"10.1089\/jop.2019.0118","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T16:56:11Z","timestamp":1594832171000},"page":"582-594","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["Corneal Stiffness and Collagen Cross-Linking Proteins in Glaucoma: Potential for Novel Therapeutic Strategy"],"prefix":"10.1177","volume":"36","author":[{"given":"Najiha","family":"Rahman","sequence":"first","affiliation":[{"name":"UCD Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"O'Neill","sequence":"additional","affiliation":[{"name":"UCD Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha","family":"Irnaten","sequence":"additional","affiliation":[{"name":"UCD Clinical Research, Catherine Mcauley Centre, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Wallace","sequence":"additional","affiliation":[{"name":"UCD Clinical Research, Catherine Mcauley Centre, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm","family":"O'Brien","sequence":"additional","affiliation":[{"name":"UCD Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland."},{"name":"UCD Clinical Research, Catherine Mcauley Centre, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.6.714"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00538-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.6.701"},{"key":"e_1_3_3_5_2","first-page":"498","article-title":"Collaborative Normal-Tension Glaucoma Study Group","volume":"126","author":"The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma","year":"1998","unstructured":"The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. 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