Fuchshofer, Rudolf (2011) The pathogenic role of transforming growth factor-beta 2 in glaucomatous damage to the optic nerve head. EXPERIMENTAL EYE RESEARCH, 93 (2). pp. 165-169. ISSN 0014-4835, 1096-0007
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In patients with primary open angle glaucoma ( POAG), the optic nerve head (ONH) shows characteristic cupping correlated with visual field defects. The progressive optic neuropathy is characterized by irreversible loss of retinal ganglion cells (RGC). The critical risk factor for axonal damage at the ONH is an elevated intraocular pressure (IOP). The increase in LOP correlates with axonal loss in the ONH, which might be due to an impaired axoplasmatic flow leading to the loss of RGCs. Damage to the optic nerve is thought to occur in the lamina cribrosa (LC) region of the ONH, which is composed of characteristic sieve-like connective tissue cribriform plates through which RGC axons exit the eye. The cupping of the optic disc, and the compression and excavation of LC are characteristic signs of glaucomatous ONH remodelling. In ONH of POAG patients a disorganized distribution and deposition of elastic fibers and a typical pronounced thickening of the connective tissue septae surrounding the optic nerve fibers is found. Transforming growth factor (TGF)-beta 2 could be one of the pathogenic factors responsible for the structural alterations in POAG patients as the TGF-beta 2 levels in the ONH of glaucomatous eyes are elevated as well as in the aqueous homour. TGF-beta 2 leads to an increased synthesis of extracellular matrix (ECM) molecules mediated by connective tissue growth factor and to an impaired ECM degradation in cultured ONH astrocytes. Bone morphogenetic protein (BMP)-4 effectively antagonizes the effects of TGF-beta 2 on matrix deposition. The BMP antagonist gremlin blocks this inhibition, allowing TGF-beta 2 stimulation of ECM synthesis. Overall, the ECM in the ONH is kept in balance in the OHN by factors that augment or block the activity of TGF-beta 2. (C) 2010 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPEN-ANGLE GLAUCOMA; HUMAN TRABECULAR MESHWORK; GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEINS; NORMAL-TENSION GLAUCOMA; AQUEOUS-HUMOR; EXTRACELLULAR-MATRIX; LAMINA-CRIBROSA; INTRAOCULAR-PRESSURE; CONNECTIVE-TISSUE; astrocytes; optic nerve head; transforming growth factor-beta; bone morphogenetic protein; extracellular matrix; connective tissue growth factor; glaucoma; gremlin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 04 May 2020 06:18 |
| Last Modified: | 04 May 2020 06:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20416 |
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