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- Sancho Pelluz, Javier, et al.
(author)
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Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation.
- 2008
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In: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49, s. 5602-5610
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Journal article (peer-reviewed)abstract
- Purpose: Resident microglial cells normally do not express sialoadhesin (a sialic acid binding receptor), whereas recruited inflammatory macrophages have been shown to do so. The expression of sialoadhesin was examined here in the course of photoreceptor cell degeneration and following transplantation. Methods: Sialoadhesin expression was analyzed in retinas of rd1 and rds mice. For transplantation studies, neonatal (P2) retinal cells derived from GFP mice were injected intraocularly in adult rd1 mice and controls. Antibodies recognizing different sialoadhesin epitopes, CD11b, and MHC-II were used to identify activated microglial cells in intact retinas and 21 days post-transplantation. Results: In rd1 mice, a few CD11b-positive cells were observed in the outer nuclear layer in the central retina at postnatal day (P) 11 and in increasing numbers between P12 21. In rds mice, CD11b-expressing cells were found from P16 and onwards. No sialoadhesin expressing cells were observed within the rd1 or rds mouse retinas at any of the ages examined (up to P150). Specific staining was only observed in cells found in the vitreal margin of the retina and in surrounding tissues (sclera, cornea, ciliary body, choroid). Following transplantation to normal and rd1 mice, a variable number of sialoadhesin-positive cells were detected within the grafts, in the graft-host interface, and in the subretinal space. Conclusions: The significant activation of microglia/macrophages observed in the various stages of degeneration in rd1 and rds mouse retinas is not accompanied by sialoadhesin expression. However, sialoadhesin-expressing cells are observed following transplantation. The occurrence of such cells could be of significance for the integration and long term survival of retinal grafts, as expression of sialoadhesin could facilitate other phagocytic receptors.
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| 2. |
- Sahaboglu, Ayse, et al.
(author)
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PARP1 Gene Knock-Out Increases Resistance to Retinal Degeneration without Affecting Retinal Function
- 2010
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11
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Journal article (peer-reviewed)abstract
- Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP) group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO) mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT) and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt). Likewise, retinal function as assessed by electroretinography (ERG) was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6), we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.
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