Tags

Type your tag names separated by a space and hit enter

AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration.
Redox Biol. 2020 10; 37:101703.RB

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.

Authors+Show Affiliations

Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: soc002@health.ucsd.edu.National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA.Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.Department of Physiology, Biophysics & Ophthalmology, University of California Irvine, Irvine, CA, 92697, USA.Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA.National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address: wju@health.ucsd.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32896719

Citation

Choi, Soo-Ho, et al. "AIBP Protects Retinal Ganglion Cells Against Neuroinflammation and Mitochondrial Dysfunction in Glaucomatous Neurodegeneration." Redox Biology, vol. 37, 2020, p. 101703.
Choi SH, Kim KY, Perkins GA, et al. AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration. Redox Biol. 2020;37:101703.
Choi, S. H., Kim, K. Y., Perkins, G. A., Phan, S., Edwards, G., Xia, Y., Kim, J., Skowronska-Krawczyk, D., Weinreb, R. N., Ellisman, M. H., Miller, Y. I., & Ju, W. K. (2020). AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration. Redox Biology, 37, 101703. https://doi.org/10.1016/j.redox.2020.101703
Choi SH, et al. AIBP Protects Retinal Ganglion Cells Against Neuroinflammation and Mitochondrial Dysfunction in Glaucomatous Neurodegeneration. Redox Biol. 2020;37:101703. PubMed PMID: 32896719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration. AU - Choi,Soo-Ho, AU - Kim,Keun-Young, AU - Perkins,Guy A, AU - Phan,Sébastien, AU - Edwards,Genea, AU - Xia,Yining, AU - Kim,Jungsu, AU - Skowronska-Krawczyk,Dorota, AU - Weinreb,Robert N, AU - Ellisman,Mark H, AU - Miller,Yury I, AU - Ju,Won-Kyu, Y1 - 2020/08/27/ PY - 2020/07/13/received PY - 2020/08/12/revised PY - 2020/08/22/accepted PY - 2020/9/9/pubmed PY - 2020/9/9/medline PY - 2020/9/8/entrez KW - AIBP KW - Glaucoma KW - Mitochondria KW - Müller glia KW - Neuroinflammation KW - Retinal ganglion cell SP - 101703 EP - 101703 JF - Redox biology JO - Redox Biol VL - 37 N2 - 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. SN - 2213-2317 UR - https://www.unboundmedicine.com/medline/citation/32896719/AIBP_protects_retinal_ganglion_cells_against_neuroinflammation_and_mitochondrial_dysfunction_in_glaucomatous_neurodegeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(20)30908-3 DB - PRIME DP - Unbound Medicine ER -