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AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration
- Source :
- Redox Biology, Vol 37, Iss, Pp 101703-(2020), Redox Biology
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Glaucoma is a leading cause of blindness worldwide in individuals 60 years of age and older. Despite its high prevalence, the factors contributing to glaucoma progression are currently not well characterized. Glia-driven neuroinflammation and mitochondrial dysfunction play critical roles in glaucomatous neurodegeneration. Here, we demonstrated that elevated intraocular pressure (IOP) significantly decreased apolipoprotein A-I binding protein (AIBP; gene name Apoa1bp) in retinal ganglion cells (RGCs), but resulted in upregulation of TLR4 and IL-1β expression in Müller glia endfeet. Apoa1bp−/− mice had impaired visual function and Müller glia characterized by upregulated TLR4 activity, impaired mitochondrial network and function, increased oxidative stress and induced inflammatory responses. We also found that AIBP deficiency compromised mitochondrial network and function in RGCs and exacerbated RGC vulnerability to elevated IOP. Administration of recombinant AIBP prevented RGC death and inhibited inflammatory responses and cytokine production in Müller glia in vivo. These findings indicate that AIBP protects RGCs against glia-driven neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration and suggest that recombinant AIBP may be a potential therapeutic agent for glaucoma.<br />Graphical abstract Image 1<br />Highlights • AIBP loss induces glia-driven neuroinflammation and triggers mitochondrial dysfunction in glaucomatous neurodegeneration. • AIBP regulates mechanisms protecting against mitochondrial dysfunction, Müller glia activation and RGC death. • Administration of recombinant AIBP deactivates Müller glia and protects RGCs and has therapeutic potential for glaucoma.
- Subjects :
- 0301 basic medicine
Retinal Ganglion Cells
Aging
genetic structures
Clinical Biochemistry
Mitochondrion
Neurodegenerative
Medical Biochemistry and Metabolomics
medicine.disease_cause
Eye
Biochemistry
Mice
0302 clinical medicine
Neuroinflammation
2.1 Biological and endogenous factors
Retinal ganglion cell
Aetiology
lcsh:QH301-705.5
Muller glia
lcsh:R5-920
Neurodegeneration
Pharmacology and Pharmaceutical Sciences
Up-Regulation
Mitochondria
medicine.anatomical_structure
5.1 Pharmaceuticals
Development of treatments and therapeutic interventions
lcsh:Medicine (General)
Research Paper
medicine.medical_specialty
Müller glia
Retinal ganglion
AIBP
03 medical and health sciences
Downregulation and upregulation
Internal medicine
medicine
Animals
Eye Disease and Disorders of Vision
business.industry
Animal
Organic Chemistry
Neurosciences
Glaucoma
medicine.disease
eye diseases
Disease Models, Animal
030104 developmental biology
Endocrinology
lcsh:Biology (General)
Disease Models
Biochemistry and Cell Biology
sense organs
business
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....9830cca90722034f5a3b5590c82ca689