中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4918-4919.doi: 10.4103/NRR.NRR-D-25-01399

• 观点:退行性病与再生 • 上一篇    下一篇

针对β-淀粉样蛋白的眼脑联合免疫治疗阿尔茨海默病：挑战和有希望的治疗途径

  

  • 出版日期:2026-10-15 发布日期:2026-06-13

Ocular-brain co-immunotherapy targeting β-amyloid in Alzheimer’s disease: challenges and promising therapeutic avenues

Xiaohong Xiang, Yong Tang, Linlin Song, Zhuohan Li, Betty Yuen Kwan Law*   

  1. Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region, China (Xiang X, Song L, Law BYK) 
    Department of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China (Xiang X) 
    College of Integration of Traditional Chinese and Western Medicine & The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China (Tang Y)
  • Online:2026-10-15 Published:2026-06-13
  • Contact: Betty Yuen Kwan Law, PhD, yklaw@must.edu.mo.
  • Supported by:
    This work was supported by grants from the Macao Science and Technology Development Fund, grant numbers 0046/2024/AGJ and 0048/2024/RIA1; The open project of Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery funded by Macau Science and Technology Development Fund (Macau University of Science and Technology, 002/2023/ALC, 006/2023/SKL), Macau Special Administrative Region (all to BYKL); LuZhou Science and Technology Program, grant number 2023RCM190 (to ZL).

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摘要： https://orcid.org/0000-0002-8926-3960 (Betty Yuen Kwan Law)

Abstract: Alzheimer’s disease is an ocular-brain comorbidity: Alzheimer’s disease (AD) is a leading neurodegenerative disorder affecting the central nervous system (CNS), clinically characterized by progressive cognitive decline, neuropsychiatric disturbances, and memory deficits. Around 60%–70% of dementia cases are due to AD, making it the most prevalent form. Current estimates suggest that approximately 50 million individuals globally are affected by AD, and the number of dementia patients is expected to rise to 139 million in 2050, with the cost of care projected to increase to nearly $1 trillion (Guo et al., 2024). The pathological hallmarks of AD predominantly consist of senile plaques, resulting from the accumulation of amyloid-beta (Aβ), and neurofibrillary tangles, arising from the hyperphosphorylation of tau protein. These features are accompanied by neuroinflammation, synaptic damage, and neuronal loss. AD is an ocular-brain comorbidity. During embryogenesis, both the retina and the brain develop from the neuroectoderm, resulting in shared anatomical, physiological, and embryological characteristics, including similarities in cell types, vasculature, and immune responses. The retina maintains structural and functional connections with the brain via the optic nerve, which links to the thalamus, optic radiation, and visual cortex. The deposition of Aβ has been observed in the postmortem eyes of AD patients and in the eyes of animal models of AD (Gaire et al., 2024). Aβ predominantly accumulates along blood vessels in the inner retinal layers, optic nerve axon bundles, meningeal lymphatic vessels of the optic nerve, and periorbital lymphatic vessels (Cao et al., 2024). Retinal Aβ is likely to originate from the brain rather than local retinal metabolism (Cao et al., 2024). Notably, Aβ can migrate from the brain to the eye within 60 minutes. The proposed mechanisms for the transport of Aβ from the brain to the eye encompass several pathways: (1) Aβ transportation along the subarachnoid space and the optic nerve sheath, with entry into the optic nerve axons via perivascular spaces; (2) axonal transport within the optic nerve directed toward the proximal optic nerve; and (3) diffusion through the perivascular spaces of the central retinal artery into the retina (Cao et al., 2024). The clearance of Aβ in the eye involves multiple processes: (1) Aβ uptake by retinal ganglion cells, followed by axonal transport through the lamina cribrosa and subsequent clearance via the meningeal lymphatic vessels of the optic nerve sheath and periorbital lymphatics; (2) glymphatic clearance facilitated by aquaporin-4 along the perivascular spaces; (3) phagocytosis and degradation by glial cells, including microglia and astrocytes; and (4) efflux across the blood–retina barrier into the systemic circulation for peripheral metabolism. The efficiency of Aβ clearance is modulated by various factors, including the cranio-ocular pressure gradient, expression levels of aquaporin-4, exposure to light, and the administration of cycloplegic agents.