Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human optic nerve contains a heterogeneous population of astrocytes. In situ, a specialized subpopulation of astrocytes was distinguished in the adult optic nerve head by expression of neural cell adhesion molecule (NCAM). To further study the biology of astrocytes, we have developed and characterized cells grown from explanted optic nerve heads and myelinated optic nerves as in vitro model systems. Second or third passage cells were processed for immunocytochemistry using antibodies against glial fibrillary acidic protein (GFAP) and cell surface epitopes: CD56/NCAM, HNK-1/NCAM, A2B5, and O4. Synthesis and gene expression of NCAM were characterized by Western blot analysis and RNase protection assay. Cells grown from myelinated optic nerves expressing GFAP, but not NCAM or A2B5, were identified as type 1A astrocytes, and cells expressing GFAP and A2B5, but not NCAM, were identified as type 2 astrocytes. Cells grown from explanted optic nerve head expressing GFAP, NCAM, and O4 were identified as type 1B astrocytes. Expression of NCAM by type 1B astrocytes may provide these cells with adhesion properties that allow them specialized responses in their microenvironment. Astrocytes from the lamina cribrosa may form a functional barrier to prevent myelination of the retina. In glaucoma, these astrocytes may be exposed to stresses due to fluctuation in intraocular pressure and therefore participate in the optic nerve changes associated with glaucomatous optic neuropathy.
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PMID:Expression of neural cell adhesion molecule (NCAM) characterizes a subpopulation of type 1 astrocytes in human optic nerve head. 921 35

Glaucomatous optic neuropathy is a common blinding disease characterized by remodeling of the extracellular matrix (ECM) and loss of retinal ganglion cell (RGC) axons at the level of the optic nerve head (ONH). Astrocytes, the major cell type in ONH, may participate in this process by production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). In normal and glaucomatous ONH, we detected MMP and TIMP expression by immunohistochemistry. Cultured astrocytes were used to characterize expression of MMPs and TIMPs by zymography, Western blot, and RNase protection assay. MMP production was stimulated with phorbol 12-myristate 13-acetate (PMA). Astrocytes expressed MMP1, MT1-MMP, MMP2, TIMP1, and TIMP2 in normal and glaucomatous ONH. MMP2, TIMP1, and TIMP2 localized to RGCs and their axons. Increased MMP1 and MT1-MMP expression was demonstrated in glaucoma. Cultured astrocytes constitutively expressed MMP2, MT1-MMP, TIMP1, and TIMP2, whereas MMP3, MMP7, MMP9, and MMP12 were not detectable in tissues or in cultured astrocytes. Our findings demonstrate the presence of specific MMPs and TIMPs in the ONH that may participate in the homeostasis and remodeling of the ECM in glaucoma. Expression of the same MMPs and TIMPs in cultured ONH astrocytes will allow further studies on the mechanisms regulating these enzymes.
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PMID:Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes. 1124 38

Glaucoma is a vision-threatening disorder characterized by progressive death of retinal ganglion cells (RGCs), although little is known about therapeutic milestones. Due to its complex and multifactorial pathogenesis, multipronged therapeutic approach is needed. Angiogenin (ANG), now called ribonuclease (RNase) 5, has been previously known as angiogenic factor and more recently its biologic activity is extended to promoting cell survival via its ribonucleolytic activity. Here, we revealed the defect of ANG in human glaucomatous trabecular meshwork (TM) cells and identified novel multiple functions of ANG as an anti-glaucomatous strategy. ANG was highly expressed in normal eyes and normal TM cells compared to glaucomatous TM cells. ANG induced intraocular pressure (IOP) lowering in rat models of both normal and elevated IOP, and as a possible mechanism, activated Akt-mediated signals for nitric oxide (NO) production, an important regulator of IOP in glaucomatous TM cell. Moreover, we demonstrated ANG-induced production of matrix metalloproteinase (MMP)-1 and -3 and rho-kinase inhibition for TM remodeling. For anti-glaucomatous defense optimization, ANG not only elicited immune-modulative pathways via indolamine 2,3-dioxygenase (IDO) activation in TM cells and suppression of Jurkat T cells, but also rescued neural stem cells (NSCs) from apoptosis induced by glaucomatous stress. These results demonstrate that novel multi-functional effects of ANG may have benefits against glaucoma in ocular tissues.
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PMID:Ribonuclease 5 coordinates signals for the regulation of intraocular pressure and inhibits neural apoptosis as a novel multi-functional anti-glaucomatous strategy. 2658 Nov 72