ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2012
GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins.
Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Blood Growth Factor Levels in Patients with Systemic Lupus Erythematosus: High Neuregulin-1 Is Associated with Comorbid Cardiovascular Pathology.Life (Basel, Switzerland) · 2024Article
- Mammalian Animal and Human Retinal Organ Culture as Pre-Clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics.Antioxidants (Basel, Switzerland) · 2023Article
- The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice.Neurobiology of disease · 2022Article
- Stem cell transplantation as a progressing treatment for retinitis pigmentosa.Cell and tissue research · 2022Review
- Regulations of Retinal Inflammation: Focusing on Müller Glia.Frontiers in cell and developmental biology · 2022Review
- Colony stimulating factors in the nervous system.Seminars in immunology · 2021Review
- Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?Frontiers in aging neuroscience · 2021Review
- Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration.Scientific reports · 2016Article
- Recent advances of stem cell therapy for retinitis pigmentosa.International journal of molecular sciences · 2014Review
- GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice.Journal of neuroimmunology · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe term retinitis pigmentosa (RP) comprises a heterogeneous group of hereditary and sporadic human retinal degenerative diseases. The molecular and cellular events still remain obscure, thus hiding effective therapies. Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a hematopoietic factor which plays a crucial role in protecting neuronal cells. Binding of GM-CSF to its receptor induces several intracellular signaling pathways and kinases. Here we examined whether GM-CSF has a neuroprotective effect on photoreceptor degeneration in Royal College of Surgeons (RCS) rats.
methodsGM-CSF was injected into the vitreous body of RCS rats either once at the onset of photoreceptor degeneration at day 21, or twice at day 21 and day 42. At day 84, when photoreceptor degeneration is completed, the rats were sacrificed, their eyes enucleated and processed for histological staining and counting the surviving photoreceptor nuclei. The expression of apoptosis-related factors, such as BAD, APAF1 and BCL-2 was examined by Western blot analysis. The expression of neurotrophins such as ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), and glia-derived neurotrophic actor (GDNF), as well as glial fibrillary acidic protein (GFAP) was analysed by Western blots and immunohistochemistry. The expression of JAK/STAT, ERK1/2 and SRC pathway proteins was assessed by Western blot analysis.
resultsGM-CSF protects significantly against photoreceptor degeneration in comparison to control group. After a single injection of GM-CSF at P21, a 4-fold increase of photoreceptors was observed, whereas eyes which received a repeated injection of GM-CSF at P42 showed a 10-fold increase of photoreceptors. Western blot analysis revealed a decreased BAD and an increased pBAD and BCL-2 expression, indicating changed expression profiles of apoptosis-related proteins. Neurotrophic factors examined are up-regulated, whereas GFAP was also modulated. At cell signalling levels, GM-CSF activates SRC-dependent STAT3 which is independent of JAK2, while proteins of the ERK1/2 pathway are not affected.
conclusionsThe data suggest that GM-CSF is a potent therapeutic agent in photoreceptor degeneration caused by mutation of the receptor tyrosine kinase gene (Mertk), and may be also effective in other photoreceptor degeneration.
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Registered trials
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