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Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response.
Exp Eye Res. 2012 May; 98:37-43.EE

Abstract

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Diabetes is known to alter the amount of retinal expression of the water-selective channels aquaporin 4 (AQP4). However, the function and impact of AQP4 in diabetic retinopathy is not well understood. In the present work, diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Two weeks later, AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were delivered by intravitreal injection to the eyes. Gene delivery was confirmed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting analysis. Eight weeks later, BRB breakdown was measured using Evans blue dye. Images of retinal sections were obtained and the thicknesses of the retinas were determined. Retinal leukostasis measurement was performed using acridine orange leukocyte fluorography. The mRNA levels of IL-1β, IL-6, intercellular adhesion molecule 1 (ICAM-1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined using qRT-PCR method. AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were transfected into rMC-1 cells to investigate its effect on inflammation induced by high glucose. Incubation with IL-1β or IL-6 was performed to test their effect on AQP4 expression in rMC-1 cells. In the current work, it was found that AQP4 expression was enhanced in the retina of diabetic rats. AQP4 knockdown led to exacerbation of retinopathy including enhancing retinal vascular permeability, retinal thickness, pro-inflammatory factors expression, and VEGF and GFAP expression in retinas of diabetic rats. AQP4 knockdown enhanced the expression of pro-inflammatory cytokines induced by high glucose in rMC-1 cells. In addition, AQP4 knockdown enhanced the release of IL-6 and VEGF from rMC-1 cells into the medium. Moreover, it was found that incubation with IL-1β or IL-6 suppressed AQP4 expression in rMC-1 cells. These results suggested that streptozotocin injection induced diabetes resulted in compensatory increases of AQP4 expression, and downregulation of AQP4 exacerbated diabetic retinopathy through aggravating inflammatory response, at last in part. Therefore, regulation of retinal function by AQP4 may attenuate diabetic retinopathy, offering a promising therapeutic strategy for diabetic retinopathy.

Authors+Show Affiliations

Department of Ophthalmology, First Affiliated Hospital of Second Military Medical University, Shanghai 200433, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22449442

Citation

Cui, Bei, et al. "Aquaporin 4 Knockdown Exacerbates Streptozotocin-induced Diabetic Retinopathy Through Aggravating Inflammatory Response." Experimental Eye Research, vol. 98, 2012, pp. 37-43.
Cui B, Sun JH, Xiang FF, et al. Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response. Exp Eye Res. 2012;98:37-43.
Cui, B., Sun, J. H., Xiang, F. F., Liu, L., & Li, W. J. (2012). Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response. Experimental Eye Research, 98, 37-43. https://doi.org/10.1016/j.exer.2012.02.013
Cui B, et al. Aquaporin 4 Knockdown Exacerbates Streptozotocin-induced Diabetic Retinopathy Through Aggravating Inflammatory Response. Exp Eye Res. 2012;98:37-43. PubMed PMID: 22449442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response. AU - Cui,Bei, AU - Sun,Jin-Hua, AU - Xiang,Fen-Fen, AU - Liu,Lin, AU - Li,Wen-Jie, Y1 - 2012/03/16/ PY - 2011/12/07/received PY - 2012/02/16/revised PY - 2012/02/22/accepted PY - 2012/3/28/entrez PY - 2012/3/28/pubmed PY - 2012/7/13/medline SP - 37 EP - 43 JF - Experimental eye research JO - Exp Eye Res VL - 98 N2 - Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Diabetes is known to alter the amount of retinal expression of the water-selective channels aquaporin 4 (AQP4). However, the function and impact of AQP4 in diabetic retinopathy is not well understood. In the present work, diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Two weeks later, AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were delivered by intravitreal injection to the eyes. Gene delivery was confirmed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting analysis. Eight weeks later, BRB breakdown was measured using Evans blue dye. Images of retinal sections were obtained and the thicknesses of the retinas were determined. Retinal leukostasis measurement was performed using acridine orange leukocyte fluorography. The mRNA levels of IL-1β, IL-6, intercellular adhesion molecule 1 (ICAM-1), glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined using qRT-PCR method. AQP4 shRNA (r) lentiviral particles or negative lentiviral particles were transfected into rMC-1 cells to investigate its effect on inflammation induced by high glucose. Incubation with IL-1β or IL-6 was performed to test their effect on AQP4 expression in rMC-1 cells. In the current work, it was found that AQP4 expression was enhanced in the retina of diabetic rats. AQP4 knockdown led to exacerbation of retinopathy including enhancing retinal vascular permeability, retinal thickness, pro-inflammatory factors expression, and VEGF and GFAP expression in retinas of diabetic rats. AQP4 knockdown enhanced the expression of pro-inflammatory cytokines induced by high glucose in rMC-1 cells. In addition, AQP4 knockdown enhanced the release of IL-6 and VEGF from rMC-1 cells into the medium. Moreover, it was found that incubation with IL-1β or IL-6 suppressed AQP4 expression in rMC-1 cells. These results suggested that streptozotocin injection induced diabetes resulted in compensatory increases of AQP4 expression, and downregulation of AQP4 exacerbated diabetic retinopathy through aggravating inflammatory response, at last in part. Therefore, regulation of retinal function by AQP4 may attenuate diabetic retinopathy, offering a promising therapeutic strategy for diabetic retinopathy. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/22449442/Aquaporin_4_knockdown_exacerbates_streptozotocin_induced_diabetic_retinopathy_through_aggravating_inflammatory_response_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(12)00081-4 DB - PRIME DP - Unbound Medicine ER -