2. Academic Validation
  3. AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration

AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration

  • Redox Biol. 2020 Oct;37:101703. doi: 10.1016/j.redox.2020.101703.
Soo-Ho Choi 1,  Keun-Young Kim 2,  Guy A Perkins 2,  Sébastien Phan 2,  Genea Edwards 3,  Yining Xia 4,  Jungsu Kim 4,  Dorota Skowronska-Krawczyk 5,  Robert N Weinreb 3,  Mark H Ellisman 2,  Yury I Miller 4,  Won-Kyu Ju 6
Affiliations

Affiliations

  • 1 Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: [email protected].
  • 2 National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.
  • 3 Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA.
  • 4 Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
  • 5 Department of Physiology, Biophysics & Ophthalmology, University of California Irvine, Irvine, CA, 92697, USA.
  • 6 Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: [email protected].
PMID: 32896719 DOI: 10.1016/j.redox.2020.101703
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.

Keywords

AIBP; Glaucoma; Mitochondria; Müller glia; Neuroinflammation; Retinal ganglion cell.

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