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Cystatin C uptake in the eye.

Wasselius, Johan LU ; Johansson, Kjell LU ; Håkansson, Katarina LU ; Abrahamson, Magnus LU and Ehinger, Berndt LU (2005) In Graefe's Archive for Clinical and Experimental Ophthalmology 243(6). p.583-592
Abstract
Background: As a secreted protein, cystatin C is assumed to play its role in the extracellular compartment, where it can inhibit virtually all cysteine proteases of families C1 ( cathepsin B, L, S) and C13 ( mammalian legumain-related proteases). Since many of its potential target enzymes in the eye reside in intracellular compartments, we sought evidence for a cellular uptake of the inhibitor in ocular tissues. Methods: Fluorescence-labeled human cystatin C was injected intravitreally into normal rat eyes. Ocular tissues were subsequently examined using ELISA, fluorescence microscopy, and immunohistochemistry. Cystatin C uptake was additionally studied in an in vitro retina model. Results: Cystatin C administered intravitreally in vivo is... (More)
Background: As a secreted protein, cystatin C is assumed to play its role in the extracellular compartment, where it can inhibit virtually all cysteine proteases of families C1 ( cathepsin B, L, S) and C13 ( mammalian legumain-related proteases). Since many of its potential target enzymes in the eye reside in intracellular compartments, we sought evidence for a cellular uptake of the inhibitor in ocular tissues. Methods: Fluorescence-labeled human cystatin C was injected intravitreally into normal rat eyes. Ocular tissues were subsequently examined using ELISA, fluorescence microscopy, and immunohistochemistry. Cystatin C uptake was additionally studied in an in vitro retina model. Results: Cystatin C administered intravitreally in vivo is taken up into cells of the corneal endothelium and epithelium, the epithelial cells lining the ciliary processes, and into cells in the neuroretina mostly ganglion cells) and the retinal pigment epithelium. The uptake is demonstrable also in vitro and was, in the neuroretina, found to be a high-affinity system, inhibited by cooling the specimens or by adding the microfilament polymerization inhibitor, cytochalasin D, to the medium. Conclusions: There is an active, temperature-dependent uptake system for cystatin C into several cell types in the cornea, ciliary body, and retina. The cell types that take up cystatin C are generally the same that contain endogenous cystatin C, suggesting that much or all cystatin C seen intracellularly in the normal eye may have been taken up from the surrounding extracellular space. The uptake indicates that the inhibitor may exert biological functions in intracellular compartments. It is also possible that this uptake system may regulate the extracellular levels of cystatin C in the eye. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Graefe's Archive for Clinical and Experimental Ophthalmology
volume
243
issue
6
pages
583 - 592
publisher
Springer
external identifiers
  • wos:000229903600012
  • scopus:22144494205
ISSN
1435-702X
DOI
10.1007/s00417-004-1055-z
language
English
LU publication?
yes
id
2d82fd80-2679-4e5b-ab6b-f94f0625f62c (old id 131892)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15614539&dopt=Abstract
date added to LUP
2007-07-09 10:32:46
date last changed
2017-08-20 04:16:29
@article{2d82fd80-2679-4e5b-ab6b-f94f0625f62c,
  abstract     = {Background: As a secreted protein, cystatin C is assumed to play its role in the extracellular compartment, where it can inhibit virtually all cysteine proteases of families C1 ( cathepsin B, L, S) and C13 ( mammalian legumain-related proteases). Since many of its potential target enzymes in the eye reside in intracellular compartments, we sought evidence for a cellular uptake of the inhibitor in ocular tissues. Methods: Fluorescence-labeled human cystatin C was injected intravitreally into normal rat eyes. Ocular tissues were subsequently examined using ELISA, fluorescence microscopy, and immunohistochemistry. Cystatin C uptake was additionally studied in an in vitro retina model. Results: Cystatin C administered intravitreally in vivo is taken up into cells of the corneal endothelium and epithelium, the epithelial cells lining the ciliary processes, and into cells in the neuroretina mostly ganglion cells) and the retinal pigment epithelium. The uptake is demonstrable also in vitro and was, in the neuroretina, found to be a high-affinity system, inhibited by cooling the specimens or by adding the microfilament polymerization inhibitor, cytochalasin D, to the medium. Conclusions: There is an active, temperature-dependent uptake system for cystatin C into several cell types in the cornea, ciliary body, and retina. The cell types that take up cystatin C are generally the same that contain endogenous cystatin C, suggesting that much or all cystatin C seen intracellularly in the normal eye may have been taken up from the surrounding extracellular space. The uptake indicates that the inhibitor may exert biological functions in intracellular compartments. It is also possible that this uptake system may regulate the extracellular levels of cystatin C in the eye.},
  author       = {Wasselius, Johan and Johansson, Kjell and Håkansson, Katarina and Abrahamson, Magnus and Ehinger, Berndt},
  issn         = {1435-702X},
  language     = {eng},
  number       = {6},
  pages        = {583--592},
  publisher    = {Springer},
  series       = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  title        = {Cystatin C uptake in the eye.},
  url          = {http://dx.doi.org/10.1007/s00417-004-1055-z},
  volume       = {243},
  year         = {2005},
}