Altered Expression of Metallothionein-I and -II and Their Receptor Megalin in Inherited Photoreceptor Degeneration
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1697698
- author
- Wunderlich, Kirsten LU ; Leveillard, Thierry ; Penkowa, Milena ; Zrenner, Eberhart and Perez, Maria Thereza LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Investigative Ophthalmology & Visual Science
- volume
- 51
- issue
- 9
- pages
- 4809 - 4820
- publisher
- Association for Research in Vision and Ophthalmology Inc.
- external identifiers
-
- wos:000281502700061
- scopus:77957338177
- pmid:20357188
- 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
- 2016-04-01 14:56:50
- date last changed
- 2022-04-14 20:29:53
@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 = {{Association for Research in Vision and 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}}, doi = {{10.1167/iovs.09-5073}}, volume = {{51}}, year = {{2010}}, }