Stromal‐Like Cells and Retinal Pigment Epithelium Modulate Choroidal Sprouting Through Galectin‐1‐Dependent and Independent Pathways

ABSTRACT Outer retinal function depends on two supporting tissues: the retinal pigment epithelium (RPE) and the choroid. Limited molecular information is available on the intercellular networks that sustain RPE/choroid tissue in both healthy and pathological states. Galectin‐1 (Gal1), a β‐galactoside‐binding lectin, has recently emerged as a key regulator of angiogenesis and a potential therapeutic target in vascular pathologies, including age‐related macular degeneration. Here, we studied the expression of Gal1 in the outer retina and its regulatory role in the RPE/choroid under physiological and pathological conditions. Our findings indicate that Gal1 is predominantly associated with stromal cells in the RPE/choroid. In Gal1‐deficient ( Lgals1 −/− ) mice, the RPE/choroid ultrastructure and gene expression profiles were altered, and choroidal explants exhibited reduced sprouting compared to those of wild‐type mice. Consistently, recombinant Gal1 promoted choroidal sprouting under hypoxic conditions, and stromal‐like cells modulated pro‐angiogenic and antiangiogenic gene expression in vitro under pathological conditions. Interestingly, Gal1 was also expressed by the RPE, with apical secretion under normoxia that shifted toward a basolateral phenotype under hypoxia. These findings identify stromal‐like cells and RPE as key sources of Gal1 in the choroid, highlighting its distinct roles in maintaining RPE/choroid homeostasis in healthy or pathological microenvironments.