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Young Hee Yoon, Yoo-Ri Chung, Jeong A Choi, Jae-Young Koh; Ursodeoxycholic acid attenuates endoplasmic reticulum stress-related pericyte loss in diabetic retinopathy of streptozotocin-treated mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4277.
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Loss of pericytes, an early hallmark of diabetic retinopathy (DR), results in the breakdown of blood-retinal barrier (BRB). Endoplasmic reticulum (ER) stress is thought to be involved in this process. Here, we examined the effect of ursodeoxycholic acid (UDCA) on ER stress and loss of pericytes in DR of streptozotocin (STZ)-induced diabetic mice.
Pathological endpoints examined in vivo included the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice. In addition, the induction of ER stress and unfolded protein response (UPR) were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE) or modified low-density lipoprotein (mLDL).
The diffuse leakage of fluorescein dye in angiography and decreased density of retinal capillaries were improved in UDCA-treated diabetic mice compared to non-treated diabetic group. Among the UPR markers, the expressions of markers involved in PERK pathway were increased in STZ-induced diabetic mice, as well as AGE or mLDL-exposed cultured retinal pericytes. Administration of UDCA also inhibited cell death in AGE or mLDL-exposed cultured retinal pericytes.
Taken together, our results demonstrate that UDCA attenuated both UPR induction and pericyte loss in DR. This suggests that UDCA, as a chemical chaperone that alleviates ER stress, may have protective effect and needs further evaluation for its efficacy in diabetic retinopathy.
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