GDNF-induced osteopontin from Müller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration
- PMID:21360756
- DOI: 10.1002/glia.21155
GDNF-induced osteopontin from Müller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration
Abstract
Glial cell line-derived neurotrophic factor (GDNF) enhances the survival of a variety of neurons, including photoreceptors (PR) in the retina. In contrast to most other GDNF receptive neurons, GDNF does, however, not exert its neuroprotective activity directly on PR neurons but transmits it indirectly by inducing expression of yet unknown neurotrophic factors in retinal Müller glial (RMG) cells. Genome-wide differential transcriptome analyses of GDNF-treated mouse retinas revealed 30 GDNF-induced transcripts containing a total of six genes coding for secreted molecules. Among them was (OPN), a secreted glycoprotein which was expressed in mouse RMG and secreted from primary mouse RMG in culture. Furthermore, OPN secretion was significantly upregulated on GDNF treatment of primary RMG. To validate, whether OPN could qualify as a neuroprotective factor for PR, we evaluated its potential neurotrophic activity on isolated PR in vitro as well as on retinal explants from the retinal degeneration 1 (Pde6brd1) mouse mutant. OPN exerted a significant, positive survival effect on primary porcine PR cells in a concentration-dependent manner and induced activation of PI3K/Akt pro-survival pathway. Moreover, in retinal explant cultures from Pde6brd1 mice, OPN significantly reduced the percentage of apoptotic cells to levels comparable with that observed in explants from wild-type mice and led to survival of significantly more PR in long-term retinal explant cultures. Our findings suggest that RMG-derived OPN is a novel candidate protein that transmits part of the GDNF-induced neuroprotective activity of RMG to PR cells.
Similar articles
- Does GDNF exert its neuroprotective effects on photoreceptors in the rd1 retina through the glial glutamate transporter GLAST?Delyfer MN, Simonutti M, Neveux N, Léveillard T, Sahel JA.Delyfer MN, et al.Mol Vis. 2005 Sep 1;11:677-87.Mol Vis. 2005.PMID:16163265
- Cyr61 activates retinal cells and prolongs photoreceptor survival in rd1 mouse model of retinitis pigmentosa.Kucharska J, Del Río P, Arango-Gonzalez B, Gorza M, Feuchtinger A, Hauck SM, Ueffing M.Kucharska J, et al.J Neurochem. 2014 Jul;130(2):227-40. doi: 10.1111/jnc.12704. Epub 2014 Mar 27.J Neurochem. 2014.PMID:24593181
- Gene therapy for detached retina by adeno-associated virus vector expressing glial cell line-derived neurotrophic factor.Wu WC, Lai CC, Chen SL, Xiao X, Chen TL, Tsai RJ, Kuo SW, Tsao YP.Wu WC, et al.Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3480-8.Invest Ophthalmol Vis Sci. 2002.PMID:12407159
- Programmed cell death in retinal degeneration: targeting apoptosis in photoreceptors as potential therapy for retinal degeneration.Marigo V.Marigo V.Cell Cycle. 2007 Mar 15;6(6):652-5. doi: 10.4161/cc.6.6.4029. Epub 2007 Mar 17.Cell Cycle. 2007.PMID:17374995Review.
- Neurotrophin family members as neuroprotectants in retinal degenerations.Abed E, Corbo G, Falsini B.Abed E, et al.BioDrugs. 2015 Feb;29(1):1-13. doi: 10.1007/s40259-014-0110-5.BioDrugs. 2015.PMID:25408174Review.
Cited by
- The Effect of Plasma Rich in Growth Factors on Microglial Migration, Macroglial Gliosis and Proliferation, and Neuronal Survival.Ruzafa N, Pereiro X, Fonollosa A, Araiz J, Acera A, Vecino E.Ruzafa N, et al.Front Pharmacol. 2021 Feb 26;12:606232. doi: 10.3389/fphar.2021.606232. eCollection 2021.Front Pharmacol. 2021.PMID:33716738Free PMC article.
- Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration.Shigesada N, Shikada N, Shirai M, Toriyama M, Higashijima F, Kimura K, Kondo T, Bessho Y, Shinozuka T, Sasai N.Shigesada N, et al.Cell Mol Life Sci. 2024 Jan 22;81(1):51. doi: 10.1007/s00018-023-05087-x.Cell Mol Life Sci. 2024.PMID:38252153Free PMC article.
- Photoreceptor preservation induced by intravitreal controlled delivery of GDNF and GDNF/melatonin in rhodopsin knockout mice.García-Caballero C, Lieppman B, Arranz-Romera A, Molina-Martínez IT, Bravo-Osuna I, Young M, Baranov P, Herrero-Vanrell R.García-Caballero C, et al.Mol Vis. 2018 Nov 16;24:733-745. eCollection 2018.Mol Vis. 2018.PMID:30581280Free PMC article.
- Immunological Insights in Equine Recurrent Uveitis.Degroote RL, Deeg CA.Degroote RL, et al.Front Immunol. 2021 Jan 8;11:609855. doi: 10.3389/fimmu.2020.609855. eCollection 2020.Front Immunol. 2021.PMID:33488614Free PMC article.Review.
- Osteopontin is a biomarker for early autoimmune uveoretinitis.Kim J, Ahn M, Choi Y, Chun J, Jung K, Tanaka A, Matsuda H, Shin T.Kim J, et al.Neural Regen Res. 2022 Jul;17(7):1604-1608. doi: 10.4103/1673-5374.330614.Neural Regen Res. 2022.PMID:34916447Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials