NGF and VEGF effects on retinal ganglion cell fate: new evidence from an animal model of diabetes

Autor: Maria Luisa Rocco, Valeria Colafrancesco, Luigi Aloe, Alessandro Lambiase, Flavio Mantelli, Ilaria Macchi
Rok vydání: 2013
Předmět:
Retinal degeneration
Blood Glucose
Male
Retinal Ganglion Cells
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Cell Survival
Enzyme-Linked Immunosorbent Assay
Tropomyosin receptor kinase A
Retina
Diabetes Mellitus
Experimental

Rats
Sprague-Dawley

03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Nerve Growth Factor
medicine
Animals
Receptor
trkA

Antibodies
Blocking

Diabetic Retinopathy
business.industry
Retinal Degeneration
General Medicine
Anatomy
medicine.disease
Immunohistochemistry
Rats
Vascular endothelial growth factor
Ophthalmology
Vascular endothelial growth factor A
Disease Models
Animal

medicine.anatomical_structure
Nerve growth factor
Endocrinology
Retinal ganglion cell
chemistry
030221 ophthalmology & optometry
sense organs
Ophthalmic Solutions
business
030217 neurology & neurosurgery
Zdroj: European journal of ophthalmology. 24(2)
ISSN: 1724-6016
Popis: To investigate if the survival effects of nerve growth factor (NGF) eyedrops on retinal ganglion cell (RGCs) are related to vascular endothelial growth factor (VEGF) in a rat model of diabetic retinopathy.Diabetes was induced in adult rats by streptozotocin injection and changes in the NGF/TrkA and VEGF retina levels were related to the progression of RGC loss. Diabetic rats were subjected to administration of NGF eyedrops or intraocular injection of anti-NGF antibody. All morphologic, immunohistochemical, and biochemical analyses were performed on whole retinas dissected after 7 or 11 weeks after diabetes induction.Diabetes was successfully induced in rats as shown by glycemic levels250 mg/dL. The NGF levels increased in diabetic retinas at 7 weeks and decreased at 11 weeks, while VEGF levels increased at all time points. The RGC loss in diabetic retinopathy worsened with anti-NGF administration, which did not alter retina VEGF levels significantly. Administration of NGF eyedrops restored TrkA levels in the retina, and protected RGCs from degeneration without influencing VEGF levels.The early increase of NGF in diabetic retina might be an endogenous response for protecting RGCs from degeneration. This protective mechanism is impaired at 11 weeks following diabetes induction, and results in a marked RGC degeneration that is improved by exogenous NGF administration and worsened by anti-NGF. The observed NGF-induced neuroprotection on damaged RGCs was not associated with changes in VEGF retina levels, which were constantly high in diabetic rats and were not altered by anti-NGF administration.
Databáze: OpenAIRE