TY - JOUR
T1 - Shear stress modulates inner blood retinal barrier phenotype
AU - Molins, Blanca
AU - Mora, Adriana
AU - Romero-Vázquez, Sara
AU - Pascual-Méndez, Anna
AU - Rovira, Sara
AU - Figueras-Roca, Marc
AU - Balcells, Mercedes
AU - Adán, Alfredo
AU - Martorell, J.
N1 - Funding Information:
This work was supported by a grant from the Ministry of Economy and Innovation of Spain ( SAF2017-84773-C2-1-R ).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/10
Y1 - 2019/10
N2 - The vascular endothelium responds to the shear stress generated by blood flow and changes function to maintain tissue homeostasis and adapt to injury in pathological conditions. Shear stress in the retinal circulation is altered in patients with retinal vascular diseases, such as diabetic retinopathy. Therefore, we aimed to study the effect of laminar shear stress on barrier properties and on the release of proinflammatory cytokines in human retinal microvascular endothelial cells (HRMEC). HRMEC were cultured in Ibidi flow chambers and exposed to laminar shear stress (0–50 dyn/cm2) for 24–48 h. Tight junction distribution (ZO-1 and claudin-5) and cytokine production were determined by immunofluorescence and ELISA, respectively. The chemotactic effect of conditioned media exposed to shear stress was determined by measuring lymphocyte transmigration in Transwells. We found that cells exposed to moderately low shear stress (1.5 and 5 dyn/cm2) showed enhanced distribution of membrane ZO-1 and claudin-5 and decreased production of the proinflammatory cytokines IL-8, CCL2, and IL-6 compared to static conditions and high shear stress values. Moreover, conditioned media from cells exposed to low shear stress, had the lowest chemotactic effect to recruit lymphocytes compared to conditioned media from cells exposed to static and high shear stress conditions. In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC.
AB - The vascular endothelium responds to the shear stress generated by blood flow and changes function to maintain tissue homeostasis and adapt to injury in pathological conditions. Shear stress in the retinal circulation is altered in patients with retinal vascular diseases, such as diabetic retinopathy. Therefore, we aimed to study the effect of laminar shear stress on barrier properties and on the release of proinflammatory cytokines in human retinal microvascular endothelial cells (HRMEC). HRMEC were cultured in Ibidi flow chambers and exposed to laminar shear stress (0–50 dyn/cm2) for 24–48 h. Tight junction distribution (ZO-1 and claudin-5) and cytokine production were determined by immunofluorescence and ELISA, respectively. The chemotactic effect of conditioned media exposed to shear stress was determined by measuring lymphocyte transmigration in Transwells. We found that cells exposed to moderately low shear stress (1.5 and 5 dyn/cm2) showed enhanced distribution of membrane ZO-1 and claudin-5 and decreased production of the proinflammatory cytokines IL-8, CCL2, and IL-6 compared to static conditions and high shear stress values. Moreover, conditioned media from cells exposed to low shear stress, had the lowest chemotactic effect to recruit lymphocytes compared to conditioned media from cells exposed to static and high shear stress conditions. In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC.
KW - Blood-retinal barrier
KW - Inflammation
KW - Shear stress
KW - Tight junctions
KW - ZO-1
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U2 - 10.1016/j.exer.2019.107751
DO - 10.1016/j.exer.2019.107751
M3 - Article
C2 - 31394104
AN - SCOPUS:85070233305
SN - 0014-4835
VL - 187
JO - Experimental Eye Research
JF - Experimental Eye Research
M1 - 107751
ER -