CD73 Controls Ocular Adenosine Levels and Protects Retina from Light-Induced Phototoxicity

Abstract

Ocular ATP and adenosine have emerged as important signalling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging in combination with in situ enzyme histochemistry, flow cytometric analysis and single cell transcriptomics to characterize the pattern of purine metabolism in the mouse and human eyes. This study identified NTPDase1/CD39 and ecto-5’-nucleotidase/CD73 as major ecto-nucleotidases, which are selectively expressed in the optic nerve head, vascular endothelial and perivascular cells, outer segments of photoreceptors, retinal microglia, and cornea and coordinately control ATP and adenosine levels. The relevance of the CD73-adenosine axis was confirmed by flash electroretinography showing that pharmacological inhibition of CD73 in dark-adapted mouse eyes rendered the animals hypersensitive to prolonged bright light, manifested as decreased a-wave and b-wave amplitudes and a loss of retinal ganglion cells. Our study thus defines ocular adenosine metabolism as a complex and spatially integrated network and characterizes its critical role in protecting the retina from light-induced phototoxicity.

Kidney-eye metabolomics in a mouse mode of oxygen-induced retinopathy correlates with those in retinopathy of prematurity

“…Relationship with the eye ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning, and neurovascular coupling in the mammalian eye [51] . purinergic signaling which are selectively expressed in the photoreceptor layer, optic nerve head, retinal vasculature, and microglia.…”