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Altered Expression of Metallothionein-I and -II and Their Receptor Megalin in Inherited Photoreceptor Degeneration

Wunderlich, Kirsten LU ; Leveillard, Thierry; Penkowa, Milena; Zrenner, Eberhart and Perez, Maria Thereza LU (2010) In Investigative Ophthalmology & Visual Science 51(9). p.4809-4820
Abstract
PURPOSE. To examine in rodent models of retinitis pigmentosa (RP) the expression of the neuroprotectants metallothionein-I and -II and of megalin, an endocytic receptor that mediates their transport into neurons. METHODS. Gene and protein expression were analyzed in retinas of rd1 and rds mice and in those of RCS (Royal College of Surgeons) rats of various ages. Glial cell markers (cellular retinaldehyde binding protein, CRALBP; glial fibrillary acidic protein, GFAP; CD11b; and isolectin B4) were used to establish the identity of the cells. RESULTS. Metallothionein-I and -II gene expression increased with age in normal and degenerating retinas and was significantly greater in the latter. Protein expression, corresponding to... (More)
PURPOSE. To examine in rodent models of retinitis pigmentosa (RP) the expression of the neuroprotectants metallothionein-I and -II and of megalin, an endocytic receptor that mediates their transport into neurons. METHODS. Gene and protein expression were analyzed in retinas of rd1 and rds mice and in those of RCS (Royal College of Surgeons) rats of various ages. Glial cell markers (cellular retinaldehyde binding protein, CRALBP; glial fibrillary acidic protein, GFAP; CD11b; and isolectin B4) were used to establish the identity of the cells. RESULTS. Metallothionein-I and -II gene expression increased with age in normal and degenerating retinas and was significantly greater in the latter. Protein expression, corresponding to metallothionein-I + II, was first observed in rd1 mice in Muller cells at postnatal day (P) 12 and in rds mice at P16, coinciding with the onset of GFAP expression in these cells. In RCS rats, the same distribution was observed, but not until P32, long after the onset of GFAP expression. Metallothionein-I + II was observed also in a small number of microglial cells. Megalin was expressed in the nerve fiber layer and in the region of the inner and outer segments in normal animals, but expression in the outer retina was lost with age in degenerating retinas. CONCLUSIONS. Induction of metallothionein-I and -II occurs in the RP models studied and correlates with glial activation. The progressive loss of megalin suggests that transport of metallothionein- I + II into the degenerating photoreceptors (from e.g., Muller cells), could be impaired, potentially limiting the actions of these metallothioneins. (Invest Ophthalmol Vis Sci. 2010;51:4809 -4820) DOI:10.1167/iovs.09-5073 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Investigative Ophthalmology & Visual Science
volume
51
issue
9
pages
4809 - 4820
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • wos:000281502700061
  • scopus:77957338177
  • pmid:20357188
ISSN
1552-5783
DOI
10.1167/iovs.09-5073
language
English
LU publication?
yes
id
af087d46-045f-40df-ad8a-e1630e774846 (old id 1697698)
date added to LUP
2010-10-22 14:55:11
date last changed
2018-05-29 12:29:46
@article{af087d46-045f-40df-ad8a-e1630e774846,
  abstract     = {PURPOSE. To examine in rodent models of retinitis pigmentosa (RP) the expression of the neuroprotectants metallothionein-I and -II and of megalin, an endocytic receptor that mediates their transport into neurons. METHODS. Gene and protein expression were analyzed in retinas of rd1 and rds mice and in those of RCS (Royal College of Surgeons) rats of various ages. Glial cell markers (cellular retinaldehyde binding protein, CRALBP; glial fibrillary acidic protein, GFAP; CD11b; and isolectin B4) were used to establish the identity of the cells. RESULTS. Metallothionein-I and -II gene expression increased with age in normal and degenerating retinas and was significantly greater in the latter. Protein expression, corresponding to metallothionein-I + II, was first observed in rd1 mice in Muller cells at postnatal day (P) 12 and in rds mice at P16, coinciding with the onset of GFAP expression in these cells. In RCS rats, the same distribution was observed, but not until P32, long after the onset of GFAP expression. Metallothionein-I + II was observed also in a small number of microglial cells. Megalin was expressed in the nerve fiber layer and in the region of the inner and outer segments in normal animals, but expression in the outer retina was lost with age in degenerating retinas. CONCLUSIONS. Induction of metallothionein-I and -II occurs in the RP models studied and correlates with glial activation. The progressive loss of megalin suggests that transport of metallothionein- I + II into the degenerating photoreceptors (from e.g., Muller cells), could be impaired, potentially limiting the actions of these metallothioneins. (Invest Ophthalmol Vis Sci. 2010;51:4809 -4820) DOI:10.1167/iovs.09-5073},
  author       = {Wunderlich, Kirsten and Leveillard, Thierry and Penkowa, Milena and Zrenner, Eberhart and Perez, Maria Thereza},
  issn         = {1552-5783},
  language     = {eng},
  number       = {9},
  pages        = {4809--4820},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology & Visual Science},
  title        = {Altered Expression of Metallothionein-I and -II and Their Receptor Megalin in Inherited Photoreceptor Degeneration},
  url          = {http://dx.doi.org/10.1167/iovs.09-5073},
  volume       = {51},
  year         = {2010},
}