ReviewFrontiers in cell and developmental biology2026
The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.
Review in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Extracellular purinergic signaling, mediated by nucleotides such as adenosine triphosphate (ATP) and adenosine, is a critical regulator of retinal homeostasis. Within the retina, this signaling pathway is indispensable for maintaining physiological functions. Dysregulation of extracellular purine balance is a key driver of retinal pathophysiology, contributing to inflammation, pathological angiogenesis, and neurodegeneration in diseases like diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and retinopathy of prematurity (ROP). The hydrolysis of extracellular ATP to adenosine, primarily orchestrated by the sequential actions of NTPDase1/ENTPD1 (CD39) and ecto-5'-nucleotidase/NT5E (CD73), represents a fundamental mechanism for calibrating purinergic signals and shifting the microenvironment from pro-inflammatory to anti-inflammatory and protective. CD39 and CD73 are pivotal enzymes in regulating retinal purinergic equilibrium. Despite their well-characterized roles in tumor biology and cerebral pathophysiology, the expression, physiological functions, and pathological implications of CD39/CD73 in the retina remain understudied and lack systematic synthesis. This review synthesizes current understanding of the roles of CD39 and CD73 in retinal physiology and pathology, with a focus on their implications in DR, AMD, glaucoma, and ROP. Critically, this review provides the first systematic integration of their layer-specific spatial compartmentalization, context-dependent functional duality, and emerging metabolic roles in photoreceptor homeostasis. We also discuss emerging therapeutic strategies that target this pathway, addressing the growing need for translational research to preserve vision.
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