Role of A-Kinase Anchoring Protein 1 in Retinal Ganglion Cells: Neurodegeneration and Neuroprotection
Tonking Bastola,
Guy A. Perkins,
Keun-Young Kim,
Seunghwan Choi,
Jin-Woo Kwon,
Ziyao Shen,
Stefan Strack,
Won-Kyu Ju
Affiliations
Tonking Bastola
Hamilton Glaucoma Center and Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA
Guy A. Perkins
National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA
Keun-Young Kim
National Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA
Seunghwan Choi
Hamilton Glaucoma Center and Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA
Jin-Woo Kwon
Hamilton Glaucoma Center and Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA
Ziyao Shen
Hamilton Glaucoma Center and Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA
Stefan Strack
Department of Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA
Won-Kyu Ju
Hamilton Glaucoma Center and Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA
A-Kinase anchoring protein 1 (AKAP1) is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis by anchoring several proteins, including protein kinase A, to the outer mitochondrial membrane. Glaucoma is a complex, multifactorial disease characterized by a slow and progressive degeneration of the optic nerve and retinal ganglion cells (RGCs), ultimately resulting in vision loss. Impairment of the mitochondrial network and function is linked to glaucomatous neurodegeneration. Loss of AKAP1 induces dynamin-related protein 1 dephosphorylation-mediated mitochondrial fragmentation and loss of RGCs. Elevated intraocular pressure triggers a significant reduction in AKAP1 protein expression in the glaucomatous retina. Amplification of AKAP1 expression protects RGCs from oxidative stress. Hence, modulation of AKAP1 could be considered a potential therapeutic target for neuroprotective intervention in glaucoma and other mitochondria-associated optic neuropathies. This review covers the current research on the role of AKAP1 in the maintenance of mitochondrial dynamics, bioenergetics, and mitophagy in RGCs and provides a scientific basis to identify and develop new therapeutic strategies that could protect RGCs and their axons in glaucoma.
