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Sang A Kim, Jeong A Choi, Anna Kim, Hyo Kwon Lee, Young Hee Yoon, Junyeop Lee; Diabetes alters fenestrations and transcytosis in choriocapillaris: Insight into the pathogenesis of diabetic choroidopathy.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5240. doi: https://doi.org/.
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Choriocapillaris is fenestrated with circular openings covered by a diaphragm. Directional fenestrations and transendothelial transport through the choriocapillaris allow the movements of macromolecules between the choroid and retina. This study was designed to investigate the effect of diabetes on cellular transport in the endothelium of choriocapillaris.
We analyzed structural characteristics and functional changes in the choriocapillaris of streptozotocin-induced diabetic mice using transmission electron microscopy and immunostaining. We exposed cultured choroidal endothelial cells to high glucose or advanced glycation end products (AGEs) conditions and evaluated the expression and subcellular localization of plasmalemma-vesicle-associated protein (PLVAP) and caveloin-1-mediated transcytosis.
In the diabetic mice, choriocapillaris was progressively disorganized depending on the duration of hyperglycemia. Ultrastructure analysis revealed that choroidal endothelial cells were thickened, and the number of fenestrations was decreased, and the disoriented fenestration toward sclera were prominent in diabetic mice. In the cultured choroidal endothelial cells, high glucose or AGEs suppressed caveloin-1-mediated transcytosis and stimulated the internalization and lysosomal degradation of PLVAP, which was not mediated by VEGF signal pathway.
Chronic hyperglycemia inhibits PLVAP-mediated fenestration and endothelial transport in the choriocapillaris. Transendothelial transport of macromolecules between choroid and retina is compromised in diabetes. Structural and functional abnormalities in diabetic choroid causes potential retinal undernutrition and accumulation of metabolic wastes, which could be one of the major pathogenesis of vision-threatening diabetic chorioretinopathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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