Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein S-thiolation is a process in which under oxidative stress, vulnerable sulfhydryl groups of proteins are conjugated to non-protein thiols such as glutathione (GSH) or cysteine resulting in the formation of protein-thiol mixed disulfides, protein-S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC). This process spontaneously disrupts the redox homeostasis of the cells, which in turn leads to functional disturbances in the respective tissue. In the ocular lens, such modification of proteins may trigger a cascade of events starting with the alteration of protein conformation, protein/enzyme deactivation, protein-S-S-protein aggregation and eventually lens opacification or cataract. Generally, the first line of defense system in the cells protects the lens proteins against such damage. Recent studies in our laboratory have shown that in addition to this defense system, lens cells also possess a well developed system to repair the oxidative damage to the lens proteins. We have identified this repair system as thioltransferase (TTase) and have proved that TTase by its dethiolase activity reverses the protein S-thiolation process which returns the oxidatively damaged lens proteins/enzymes to their original reduced state and restores their physiological functions. We investigated if this repair mechanism was mediated by enzymes other than TTase. We studied glutathione S-transferase (GST) and report here for the first time the cloning, high level expression, and purification of human lens mu and pi isoforms of GST. A comparative study of recombinant human lens TTase and GST (mu and pi) on their dethiolating abilities using lens crystallin-thiol mixed disulfides showed that the lens TTase is 60-70% more efficient in the dethiolation/repair process than GST. When TTase and GST were tested in conjunction for the dethiolation of thiol mixed disulfides, there was no significant enhancement of dethiolase activity. These findings suggest that TTase by itself is an efficient enzyme in the dethiolation/repair process and hence can be considered a crucial system to counteract oxidative stress in the lens.
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PMID:Does glutathione-S-transferase dethiolate lens protein-thiol mixed disulfides?-A comparative study with thioltransferase. 1037 35

A major complication of intraocular lens surgery is diminished visual acuity caused by the regrowth of lens epithelial cells (secondary cataract). Polymethylmethacrylate (PMMA) is a commonly used intraocular lens material. This study addresses the mechanisms underlying the initial adhesion of lens epithelial cells to PMMA and a functionalized PMMA-based terpolymer known to inhibit cell proliferation. Rabbit lens epithelial cells were cultured on the test polymer surfaces in medium containing serum depleted of either fibronectin or vitronectin (or both) to identify the role of these proteins in the initial process of cell adhesion. Adherent cells were quantitated after 60 min, and the actin cytoskeleton and focal contact formation were compared in each serum treatment on both polymers. Vitronectin was significantly more effective for initial cell attachment to both polymers than fibronectin. Normal cell spreading on PMMA required vitronectin and was independent of fibronectin, whereas cell spreading on the terpolymer was abnormal and required the presence of fibronectin and vitronectin together. Together, these results help to explain the inhibition of cell proliferation previously shown on the functionalized PMMA. This work contributes to the design of a polymer for use in intraocular lenses that inhibits proliferation of the target cells.
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PMID:Vitronectin is significant in the adhesion of lens epithelial cells to PMMA polymers. 1512 94

Pseudoexfoliation syndrome is an ocular manifestation of a systemic elastosis. Exact etiology of this condition remains unknown. The basic pathogenetic concept of PEX is a pathological process of the extracellular matrix, characterized by the excessive production of an abnormal extracellular material which aggregates and accumulates and is not degraded in vivo. This material is produced primarily by the non pigmented epithelium of the ciliary body, the posterior iris pigment epithelium, and the preequatorial lens epithelium, while the corneal endothelium, trabecular cells, and vascular endothelia and smooth muscle cells of the iris have also been implicated. PEX material has a complex glycoprotein/proteoglycan, composition containing glycosaminoglycans (heparan sulfate, chondroitin sulfate, dermatan sulfate, hyaluronic acid). The prevailing presence of elastic fiber epitopes, mainly elastic microfibrillar components (elastin, vitronectin, amyloid P, fibrillin-1, LTBP-1), has led to the current theory explaining PEX as a type of elastosis, affecting especially elastic microfibrils. Ocular deposition of pseudoexfoliation material can lead to many complications in intraocular surgery like increased risk of zonular dehiscence, capsular rupture, vitreous loss during cataract extraction. Special attention is required before, during and after surgery.
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PMID:[Pseudoexfoliation syndrome--etiopatogenesis and clinical course]. 1688 48

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. XFS plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. It is accompanied by an increase in serious complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss. It is associated systemically with an increasing number of vascular disorders, hearing loss, and Alzheimer's disease. XFS appears to be a disease of elastic tissue microfibrils. The characteristic fibrils, composed of microfibrillar subunits surrounded by an amorphous matrix comprising various glycoconjugates, contain predominantly epitopes of elastic fibers, such as elastin, tropoelastin, amyloid P, vitronectin, and components of elastic microfibrils, such as fibrillin-1, fibulin-2, vitronectin, microfibril-associated glycoprotein (MAGP-1), and latent TGF-beta binding proteins (LTBP-1 and LTBP-2), the proteoglycans syndecan and versican, the extracellular chaperone clusterin, the cross-linking enzyme lysyl oxidase, and other proteins. A recent milestone study showed that two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodeling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protein disorder.
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PMID:The management of exfoliative glaucoma. 1892 11