Forskolin attenuates retinal inflammation in diabetic mice

You,Zhi‑Peng; Xiong,Bin; Zhang,Yu‑Lan; Shi,Lu; Shi,Ke

doi:10.3892/mmr.2017.8106

February-2018 Volume 17 Issue 2

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February-2018 Volume 17 Issue 2

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Article Open Access

Forskolin attenuates retinal inflammation in diabetic mice

Authors:
- Zhi‑Peng You
- Bin Xiong
- Yu‑Lan Zhang
- Lu Shi
- Ke Shi
View Affiliations / Copyright

Affiliations: Department of Ophthalmology, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China

Copyright: © You et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 2321-2326
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Published online on: November 20, 2017

https://doi.org/10.3892/mmr.2017.8106
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Abstract

The present study aimed to investigate the effect of forskolin on retinal inflammation under diabetic conditions. C57BL/6 mice were randomly divided into normal control, diabetic control and forskolin treatment groups. The diabetic model was established by intraperitoneal injection of streptozotocin. The forskolin treatment group received intragastrical administration of forskolin for 12 weeks, the other two groups received an equal amount of PBS. At 21 weeks following diabetic induction, an immunoblotting test was conducted to investigate the expression of two inflammatory factors: Intercellular adhesion molecule-1 (ICAM‑1) and tumor necrosis factor‑α (TNF‑α). Glucose concentration was additionally calculated. A leukostasis assay was utilized to compare microvasculature pathological alterations. It was demonstrated that retinal glucose concentration of diabetic control and forskolin treatment were both increased compared with normal control, however the forskolin treatment group was only ~68.06% of the diabetic control due to downregulated glucose transporter 1 expression. The expression of ICAM‑1 and TNF‑α were upregulated in the forskolin treatment and diabetic control groups compared with the normal control, however these two inflammatory factor expression levels in the forskolin treatment group were ~68.75 and 75.37% of diabetic control. It was additionally observed that there were less adherent leukocytes in retinal microvasculature in the forskolin treatment group compared with diabetic control. All the differences observed were significant. Overall, by means of limiting glucose transport into the retina via forskolin, the retinal environment with lower glucose concentration alleviates the inflammatory response under diabetic conditions.

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1	International Diabetes Federation (IDF), . IDF Diabetes Atlas. 7th. IDF; Brussels: 2015
2	Wong TY, Simó R and Mitchell P: Fenofibrate-a potential systemic treatment for diabetic retinopathy. Am J Ophthalmol. 154:6–12. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sjølie AK, Dodson P and Hobbs FR: Does renin-angiotensin system blockade have a role in preventing diabetic retinopathy? A clinical review. Int J Clin Pract. 65:148–153. 2011. View Article : Google Scholar : PubMed/NCBI
4	Chen M, Curtis TM and Stitt AW: Advanced glycation end products and diabetic retinopathy. Curr Med Chem. 20:3234–3240. 2013. View Article : Google Scholar : PubMed/NCBI
5	Tang J and Kern TS: Inflammation in diabetic retinopathy. Prog Retin Eye Res. 30:343–358. 2011. View Article : Google Scholar : PubMed/NCBI
6	Roy S, Kern TS, Song B and Stuebe C: Mechanistic insights into pathological changes in the diabetic retina: Implications for targeting diabetic retinopathy. Am J Pathol. 187:9–19. 2017. View Article : Google Scholar : PubMed/NCBI
7	Silva PS, Sun JK and Aiello LP: Role of steroids in the management of diabetic macular edema and proliferative diabetic retinopathy. Semin Ophthalmol. 24:93–99. 2009. View Article : Google Scholar : PubMed/NCBI
8	Thorens B and Mueckler M: Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab. 298:E141–E145. 2010. View Article : Google Scholar : PubMed/NCBI
9	Lu L, Seidel CP, Iwase T, Stevens RK, Gong YY, Wang X, Hackett SF and Campochiaro PA: Suppression of GLUT1; a new strategy to prevent diabetic complications. J Cell Physiol. 228:251–257. 2013. View Article : Google Scholar : PubMed/NCBI
10	Fu S, Dong S, Zhu M, Sherry DM, Wang C, You Z, Haigh JJ and Le YZ: Müller glia are a major cellular source of survival signals for retinal neurons in diabetes. Diabetes. 64:3554–3563. 2015. View Article : Google Scholar : PubMed/NCBI
11	Agrawal NK and Kant S: Targeting inflammation in diabetes: Newer therapeutic options. World J Diabetes. 5:697–710. 2014. View Article : Google Scholar : PubMed/NCBI
12	Wang J, Xu X, Elliott MH, Zhu M and Le YZ: Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes. 59:2297–2305. 2010. View Article : Google Scholar : PubMed/NCBI
13	Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK prospective diabetes study (UKPDS) group. Lancet. 352:837–853. 1998. View Article : Google Scholar : PubMed/NCBI
14	Stophen J and Ryan R: Retina. 4th. Elsevier; Singapore: 2010
15	Kumagai AK, Vinores SA and Pardridge WM: Pathological upregulation of inner blood-retinal barrier Glut1 glucose transporter expression in diabetes mellitus. Brain Res. 706:313–317. 1996. View Article : Google Scholar : PubMed/NCBI
16	Tian P, Ge H, Liu H, Kern TS, Du L, Guan L, Su S and Liu P: Leukocytes from diabetic patients kill retinal endothelial cells: Effects of berberine. Mol Vis. 19:2092–2105. 2013.PubMed/NCBI
17	Zhang HT, Shi K, Baskota A, Zhou FL, Chen YX and Tian HM: Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats. Eur J Pharmacol. 740:233–239. 2014. View Article : Google Scholar : PubMed/NCBI
18	Zhang Q and Steinle JJ: IGFBP-3 inhibits TNF-α production and TNFR-2 signaling to protect against retinal endothelial cell apoptosis. Microvasc Res. 95:76–81. 2014. View Article : Google Scholar : PubMed/NCBI
19	Lutty GA: Effects of diabetes on the eye. Invest Ophthalmol Vis Sci. 54:ORSF81–ORSF87. 2013. View Article : Google Scholar : PubMed/NCBI
20	Noda K, Nakao S, Zandi S, Sun D, Hayes KC and Hafezi-Moghadam A: Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: New insight on the inflammatory paradigm. FASEB J. 28:2038–2046. 2014. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Forskolin attenuates retinal inflammation in diabetic mice

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