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Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 22, Iss 7581, p 7581 (2021), Volume 22, Issue 14
- Publication Year :
- 2021
-
Abstract
- Glaucoma is a leading cause of irreversible blindness worldwide, and increased intraocular pressure (IOP) is a major risk factor. We aimed to determine if early functional and molecular differences in the glaucomatous retina manifest before significant retinal ganglion cell (RGC) loss is apparent. Adenoviral vectors expressing a pathogenic form of myocilin (Ad5.MYOC) were used to induce IOP elevation in C57BL/6 mice. IOP and pattern electroretinograms (pERG) were recorded, and retinas were prepared for RNA sequencing, immunohistochemistry, or to determine RGC loss. Ocular injection of Ad5.MYOC leads to reliable IOP elevation, resulting in significant loss of RGC after nine weeks. A significant decrease in the pERG amplitude was evident in eyes three weeks after IOP elevation. Retinal gene expression analysis revealed increased expression for 291 genes related to complement cascade, inflammation, and antigen presentation in hypertensive eyes. Decreased expression was found for 378 genes associated with the γ-aminobutyric acid (GABA)ergic and glutamatergic systems and axon guidance. These data suggest that early functional changes in RGC might be due to reduced GABAA receptor signaling and neuroinflammation that precedes RGC loss in this glaucoma model. These initial changes may offer new targets for early detection of glaucoma and the development of new interventions.
- Subjects :
- 0301 basic medicine
Male
Retinal Ganglion Cells
Intraocular pressure
genetic structures
Glaucoma
neuroinflammation
chemistry.chemical_compound
Mice
0302 clinical medicine
Biology (General)
GABAergic Neurons
Spectroscopy
gamma-Aminobutyric Acid
General Medicine
Computer Science Applications
Chemistry
medicine.anatomical_structure
Retinal ganglion cell
GABAergic
Female
medicine.medical_specialty
QH301-705.5
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Ophthalmology
medicine
retinal ganglion cell loss
Animals
Physical and Theoretical Chemistry
Eye Proteins
QD1-999
Molecular Biology
Myocilin
Neuroinflammation
Intraocular Pressure
Glycoproteins
Inflammation
myocilin
pattern electroretinography
Retina
γ-aminobutyric acid (GABA)
business.industry
Organic Chemistry
Retinal
medicine.disease
eye diseases
Mice, Inbred C57BL
Cytoskeletal Proteins
Disease Models, Animal
030104 developmental biology
chemistry
Gene Expression Regulation
030221 ophthalmology & optometry
sense organs
business
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....eb1bbb08f004557da7a34bcca594a653