《生命科学》 2026, 38(7): 1336-1344
周细胞调控眼部新生血管的研究进展
摘 要：
病理性眼部新生血管（pathological ocular neovascularization）是多种致盲性眼病的共同病理特征，是在多种 细胞成分和多种病理因素互相包含、交互影响下形成的。其发病率呈现持续增高的趋势，目前已成为威胁人群视觉 健康的重要公共卫生问题。目前临床上以抗VEGF治疗为主，但是也存在应答率有限、依从性差等问题，因此迫切需 要探究新的发病机制，寻找新的治疗靶点。近年来的研究发现，周细胞（pericytes，PCs）通过PDGF-B/PDGFR-β信号 通路被招募，分泌TGF-β、Ang-1等因子来调控血管成熟、血流稳态以及血-组织屏障完整性。本文将深入探讨周细胞 的生物学特性、新生血管生成的机制，以及周细胞在眼部新生血管生成过程中的作用，为治疗病理性眼部新生血管 提供新的思路和方向。
通讯作者：宋洪元 , Email:hongyuansong@hotmail.com
Abstract:
Pathological ocular neovascularization is a universal pathological feature of various sight-threatening eye diseases, such as diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration . Its global prevalence keeps rising, creating a mounting public health burden that severely impairs visual function and patients’ quality of life. Current clinical interventions mainly rely on pan-retinal photocoagulation and anti-VEGF therapy. Despite partial therapeutic efficacy, these approaches are limited by insufficient response rates, transient curative effects, heavy treatment burden and unsatisfactory patient adherence. Accordingly, it is urgent to unravel the complex pathogenic mechanisms underlying ocular neovascularization and develop innovative therapeutic targets. Accumulating research evidence has validated that pericytes are central modulators of retinal vascular homeostasis and pathological angiogenesis. As mural cells closely encasing endothelial layers of capillaries, arterioles and venules, pericytes establish direct physical connections with endothelial cells and participate in reciprocal signal crosstalk to coordinate vascular maturation, hemodynamic stability and blood-tissue barrier integrity. The PDGF-B/PDGFR-β signaling cascade dominates the recruitment, migration and vascular coverage of pericytes throughout vascular development and remodeling. After recruitment, pericytes secrete key regulatory cytokines including TGF-β and Ang-1, which synergistically promote vessel maturation, stabilize microcirculation and sustain barrier function. Additionally, pericytes exhibit prominent functional plasticity. Under developmental or pathological stimuli, they may undergo dedifferentiation, proliferation or transdifferentiation into fibroblasts, smooth muscle cells and mesenchymal stem cells, thus dynamically regulating vascular remodeling, tissue repair and fibrotic progression. Recent studies have pinpointed pericyte dysfunction as a pivotal factor facilitating the progression of pathological ocular neovascularization. In retinopathy of prematurity, hyperoxia provokes intracellular Ca2+ overload and α-SMA-mediated vasoconstriction, leading to capillary obliteration. Subsequent retinal ischemia elevates HIF-1α expression to induce excessive VEGF secretion, while impaired Ang-2/Tie2 signaling further accelerates pericyte shedding and vascular destabilization. Early pericyte loss is acknowledged as the hallmark pathological alteration of diabetic retinopathy; hyperglycemia triggers oxidative stress, mitochondrial damage and advanced glycation end-product deposition, jointly disrupting the pericyte microenvironment and triggering pericyte apoptosis and subsequent microvascular lesions. In age- related macular degeneration, early pericyte apoptosis causes choroidal capillary atrophy and Bruch’s membrane rupture, and pericyte-myofibroblast transformation further drives subretinal fibrosis. During corneal neovascularization, PDGF-B/PDGFR-β signaling mediates pericyte recruitment to pathological vessels and aggravates abnormal angiogenesis. Chronic ischemia-induced pericyte dysfunction also reshapes iris vasculature and eventually induces neovascular glaucoma. In conclusion, pericytes are indispensable for maintaining ocular microvascular homeostasis. Pericyte depletion, phenotypic transformation and abnormal activation represent core mechanisms underlying the initiation and progression of pathological ocular neovascularization. This review systematically summarizes the regulatory roles of pericytes in multiple ocular neovascular disorders. Further investigations into pericyte-related signaling pathways in the ocular microenvironment will provide novel intervention strategies, offering theoretical support for developing long-term, effective and individualized therapies for blinding neovascular eye diseases.
Communication Author：SONG Hong-Yuan , Email:hongyuansong@hotmail.com
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