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NGF/anti-VEGF combined exposure protects RCS retinal cells and photoreceptors that underwent a local worsening of inflammation
- Source :
- Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 255(3)
- Publication Year :
- 2016
-
Abstract
- Our previous study highlighted the potential nerve growth factor (NGF) effect on damaged photoreceptors from a rat model of spontaneous Retinitis Pigmentosa (RP). Herein, we tested the combined NGF/anti-vascular endothelial growth factor (αVEGF) effect on cultured retinal cells isolated from Royal College of Surgeons (RCS) rats receiving an intravitreal VEGF injection (iv-VEGF) to exacerbate retinal inflammation/neovascularization. RCS (n = 75) rats were equally grouped as untreated (n = 25), iv-saline (single saline intravitreal injection; n = 25) and iv-VEGF (single VEGF intravitreal injection; n = 25). Morphological and biochemical analysis or in vitro stimulations with the biomolecular investigation were carried out on explanted retinas. Isolated retinal cells were treated with NGF and αVEGF, either alone or in combination, for 6 days and cells were harvested for morphological and biomolecular analyses. Infiltrating inflammatory cells were detected in iv-VEGF exposed RCS retinas, indicative of exacerbated inflammation and neovascularization. In cell cultures, NGF/αVEGF significantly increased retinal cell survival as well as rhodopsin expression and neurite outgrowth in photoreceptors. Particularly, NGF/αVEGF upregulated Bcl-2 mRNA, downregulated Bax mRNA, upregulated trkANGFR mRNA and finally upregulated both NGF mRNA and protein. These data confirm and extend our previous findings on NGF-photoreceptor crosstalk, highlighting that the NGF/αVEGF combination might be an interesting approach for improving neuroprotection of RCS retinal cells and likewise photoreceptors in the presence of neovascularization. Further studies are required to translate this in vitro approach into clinical practice.
- Subjects :
- Retinal degeneration
Male
Vascular Endothelial Growth Factor A
Neurite
Cell Survival
Inflammation
Angiogenesis Inhibitors
Apoptosis
Enzyme-Linked Immunosorbent Assay
Real-Time Polymerase Chain Reaction
Andrology
Neovascularization
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Nerve Growth Factor
Medicine
Animals
Cells, Cultured
Gene therapy of the human retina
Microscopy, Confocal
business.industry
Gene Expression Regulation, Developmental
Retinal
Anatomy
medicine.disease
Sensory Systems
Rats
Vascular endothelial growth factor
Bevacizumab
Ophthalmology
Disease Models, Animal
Nerve growth factor
chemistry
Animals, Newborn
Proto-Oncogene Proteins c-bcl-2
Intravitreal Injections
030221 ophthalmology & optometry
RNA
Female
sense organs
medicine.symptom
business
030217 neurology & neurosurgery
Retinitis Pigmentosa
Photoreceptor Cells, Vertebrate
Subjects
Details
- ISSN :
- 1435702X
- Volume :
- 255
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
- Accession number :
- edsair.doi.dedup.....5b0098d2cbcefccd5ad02c4cd1dcf1e8