Corneal Stiffness and Collagen Cross-Linking Proteins in Glaucoma: Potential for Novel Therapeutic Strategy.
Biomechanical properties of the cornea have recently emerged as clinically useful in risk assessment of diagnosing glaucoma and predicting disease progression. Corneal hysteresis (CH) is a dynamic tool, which measures viscoelasticity of the cornea. 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.
['Rahman|Najiha|N|', "O'Neill|Evelyn|E|", 'Irnaten|Mustapha|M|', 'Wallace|Deborah|D|', "O'Brien|Colm|C|"]
D000293:Adolescent D000368:Aged D000369:Aged, 80 and over D001696:Biomechanical Phenomena D002648:Child D003094:Collagen D003315:Cornea D018450:Disease Progression D005109:Extracellular Matrix D005260:Female D019204:GTP-Binding Proteins D005901:Glaucoma D006801:Humans D008297:Male D008875:Middle Aged D009900:Optic Nerve D009901:Optic Nerve Diseases D000091345:Protein Glutamine gamma Glutamyltransferase 2 D008249:Protein-Lysine 6-Oxidase D012333:RNA, Messenger D012590:Sclera D014129:Trabecular Meshwork D011503:Transglutaminases
stiffness glaucoma cornea hysteresis cross-linking enzymes