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rd1 Photoreceptor Degeneration: Photoreceptor Rescue and Role of Metalloproteases in Retinal Degeneration

Ahuja Jensen, Poonam LU (2005) In Neuroreport; J Chem Neuroanat; Neuroscience.
Abstract
The thesis is focused on an attempt to delay photoreceptor cell death in the rd1 mouse using Lens Epithelium Derived Growth Factor (LEDGF), Glutathione S-Transferase mu (GST-?? and Glutathione S-Transferase alpha (GST-?? in an organ culture paradigm as well as the role of metalloproteases (MMPs) and their tissue inhibitors in photoreceptor degeneration (TIMPs).



The rd1 mouse model displays a retina degeneration which starts around day 10 with rod photoreceptor cell death. By 21 days after birth virtually all rod photoreceptors in the retina have died, and subsequent cone degeneration starts. The latter process is somewhat slower and by the age of 3-4 months, the animal has practically no photoreceptors left. In order to... (More)
The thesis is focused on an attempt to delay photoreceptor cell death in the rd1 mouse using Lens Epithelium Derived Growth Factor (LEDGF), Glutathione S-Transferase mu (GST-?? and Glutathione S-Transferase alpha (GST-?? in an organ culture paradigm as well as the role of metalloproteases (MMPs) and their tissue inhibitors in photoreceptor degeneration (TIMPs).



The rd1 mouse model displays a retina degeneration which starts around day 10 with rod photoreceptor cell death. By 21 days after birth virtually all rod photoreceptors in the retina have died, and subsequent cone degeneration starts. The latter process is somewhat slower and by the age of 3-4 months, the animal has practically no photoreceptors left. In order to study the effect of factors which delay or halt the photoreceptor degeneration, a long term retina organ culture has been used. The culture medium of this culture paradigm was devoid of fetal calf serum (FCS) as FCS by itself contains an unknown number of growth factors which can synergistically interact on the rescue mechanisms together with the tested substance. In order to provide a chemically defined environment for the test paradigm, the culture medium was further developed to function without the addition of any FCS. Using this improved culture paradigm, a moderate but clear photoreceptor rescue was demonstrated using LEDGF. Also GSTs were tested and found to exhibit a rescue effect on photoreceptor degeneration. The mechanism(s) of photoreceptor cell death (apoptosis) in the rd1 mouse is not completely understood and is probably not involving the established caspase dependent apoptotic pathways. MMPs and TIMPs are involved in apoptotic processes. To enlighten their role in photoreceptor cell death, a study on the normal presence of these substances in the wild type retina and their changes in the rd1 mouse was performed. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr Chader, Gerald, University of Southern California
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Oftalmologi, Ophtalmology, retinal degeneration, Survival factors, metalloproteases
in
Neuroreport; J Chem Neuroanat; Neuroscience.
pages
120 pages
publisher
Ophthalmology (Lund), Lund University
defense location
Rune Grubbsalen, BMC, Sölvegatan 19, Lund
defense date
2005-04-15 13:00:00
ISSN
1652-8220
ISBN
91-85439-16-9
language
English
LU publication?
yes
additional info
AR Caffe, P Ahuja, B Holmqvist, S Azadi, J Forsell, I Holmqvist, AK Soderpalm and T van Veen. 2001. Mouse retina explants after long-term culture in serum free medium. Journal of chemical neuroanatomy, vol 22 pp 263-273. Elsevier
P Ahuja, AR Caffe, I Holmqvist, AK Soderpalm, DP Singh, T Shinohara and T van Veen. 2001. Lens epithelium-derived growth factor (LEDGF) delays photoreceptor degeneration in explants of rd/rd mouse retina. Neuroreport, vol Sept 17, 12 pp 2951-2955. Lippincott Williams and Wilkins
P Ahuja, A. R. Caffé, P Ahuja, P Ekström and T van Veen. 2005. Decreased Glutathione Transferase Levels in rd1/rd1 mouse retina, Replenishment protects photoreceptors in retinal explants. Neuroscience, vol 131 pp 935-944. Elsevier
S Ahuja, P Ahuja, AR Caffé, P Ekström, M Abrahamson and T van Veen. . rd1 Mouse Shows Imbalance in Cellular Distribution and Levels of TIMP-1/ MMP-9, TIMP-2/ MMP-2 and Sulphated Glycosaminoglycans. Opthalmic Research, (submitted)
id
b1781db9-dbf4-4541-945f-df123946818e (old id 544444)
date added to LUP
2016-04-01 15:20:09
date last changed
2019-05-22 08:12:38
@phdthesis{b1781db9-dbf4-4541-945f-df123946818e,
  abstract     = {{The thesis is focused on an attempt to delay photoreceptor cell death in the rd1 mouse using Lens Epithelium Derived Growth Factor (LEDGF), Glutathione S-Transferase mu (GST-?? and Glutathione S-Transferase alpha (GST-?? in an organ culture paradigm as well as the role of metalloproteases (MMPs) and their tissue inhibitors in photoreceptor degeneration (TIMPs).<br/><br>
<br/><br>
The rd1 mouse model displays a retina degeneration which starts around day 10 with rod photoreceptor cell death. By 21 days after birth virtually all rod photoreceptors in the retina have died, and subsequent cone degeneration starts. The latter process is somewhat slower and by the age of 3-4 months, the animal has practically no photoreceptors left. In order to study the effect of factors which delay or halt the photoreceptor degeneration, a long term retina organ culture has been used. The culture medium of this culture paradigm was devoid of fetal calf serum (FCS) as FCS by itself contains an unknown number of growth factors which can synergistically interact on the rescue mechanisms together with the tested substance. In order to provide a chemically defined environment for the test paradigm, the culture medium was further developed to function without the addition of any FCS. Using this improved culture paradigm, a moderate but clear photoreceptor rescue was demonstrated using LEDGF. Also GSTs were tested and found to exhibit a rescue effect on photoreceptor degeneration. The mechanism(s) of photoreceptor cell death (apoptosis) in the rd1 mouse is not completely understood and is probably not involving the established caspase dependent apoptotic pathways. MMPs and TIMPs are involved in apoptotic processes. To enlighten their role in photoreceptor cell death, a study on the normal presence of these substances in the wild type retina and their changes in the rd1 mouse was performed.}},
  author       = {{Ahuja Jensen, Poonam}},
  isbn         = {{91-85439-16-9}},
  issn         = {{1652-8220}},
  keywords     = {{Oftalmologi; Ophtalmology; retinal degeneration; Survival factors; metalloproteases}},
  language     = {{eng}},
  publisher    = {{Ophthalmology (Lund), Lund University}},
  school       = {{Lund University}},
  series       = {{Neuroreport; J Chem Neuroanat; Neuroscience.}},
  title        = {{rd1 Photoreceptor Degeneration: Photoreceptor Rescue and Role of Metalloproteases in Retinal Degeneration}},
  url          = {{https://lup.lub.lu.se/search/files/4369734/544452.pdf}},
  year         = {{2005}},
}