Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (5): 1414-1415.doi: 10.4103/NRR.NRR-D-24-00221

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Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration

Sinwoo Hwang, Seunghwan Choi, Soo-Ho Choi, Keun-Young Kim, Yury I. Miller, Won-Kyu Ju*    

  1. Hamilton Glaucoma Center and Shiley Eye Instttute, The Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA (Hwang S, Choi S, Ju WK)  Department of Medicine, University of California San Diego, La Jolla, CA, USA (Choi SH, Miller YI)  Nattonal Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA, USA (Kim KY) 
  • Online:2025-05-15 Published:2024-10-30
  • Contact: Won-Kyu Ju, PhD, wju@health.ucsd.edu.
  • Supported by:
    This work was supported by the Nattonal Instttutes of Health grants EY034116 (to WKJ, KYK, and SHC) and AG081037 (to YIM and WKJ).

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Abstract: Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness, affecting individuals aged 40 to 80 years worldwide. Due to the aging population, it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more prevalent. Glaucoma primarily contributes to opttc nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs), subsequently leading to vision impairment. The onset of glaucoma is affected by various factors, including genettc predisposittons, environmental influences, and physiological condittons. The major risk factors include elevated intraocular pressure (IOP), aging, genetic/ epigenettc factors, immune system dysregulatton, and vascular dysfunctton. Elevated IOP is currently the only adjustable and treatable risk factor for glaucoma through medicattons, laser procedures, and surgical interventions. However, reducing IOP by these treatments is insufffcient to manage the progression of glaucomatous optic nerve degeneration and RGC death. There is growing interest in elucidating the pathophysiological mechanisms underlying glaucoma pathogenesis, particularly regarding the involvement of gliamediated neuroinffammatton. Cholesterol is essential for the structural and functional integrity of RGCs, playing a pivotal role in maintaining cell membrane integrity, signal transduction, synaptic function, and neuroprotectton. However, excessive accumulatton of cholesterol deteriorates cellular functions by enhancing toll-like receptor (TLR) signaling, ac tivating inflammasomes, and induc ing inflammatory responses (Tall and Yvan-Charvet, 2015). Recent evidence indicates that ATPbinding cassette transporter 1 (ABCA1) deffciency triggers rettnal cholesterol accumulatton, resulttng in alterations in mitochondrial function and autophagy ffux, and RGC death (Yang et al., 2023). Addittonally, glia-speciffc ABCA1 deffciency induces cholesterol accumulatton in the astrocytes, which is linked to RGC degeneration and inflammation (Shinozaki et al., 2022).