Immunolocalization of advanced glycation end products in human diabetic eyes: an immunohistochemical study

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DOI: 10.4236/jdm.2011.13009   PDF   HTML     4,573 Downloads   7,753 Views   Citations

Abstract

Background: Advanced glycation end-products (AGEs) play a critical role in the pathology of diabetic complications. The aim of this study is to examine the immunolocalization of advanced glycation end products (AGE) and receptor for AGE (RAGE) in human diabetic and non-diabetic donor eyes using immunohistochemistry. Materials and Methods: Eight globes were obtained from human postmortem donors: six diabetic donors and two non-diabetic. Formalin-fixed, paraffin-embedded tissue sections were subjected to immunohistochemistry with anti-AGE, and RAGE antibodies. Results: In eyes from diabetic donors, the blood vessels of the iris and choroid had relatively thickened walls. The ciliary body showed decreased capillaries with hyalinization in the stroma. Neovascularization or proliferative changes were not observed in the tissues. Immunoreactivity for AGE was highly detected in the stroma and blood vessels of the iris, ciliary body, choriocapillaris, choroidal large vessels, and central retinal artery/vein. Immunoreactivity was also detected in the retina, corneal endothelium, and lens. RAGE immunoreactivity was weakly detected in choroidal vessels and Bruch’s membrane. In eyes from non-diabetic donors, AGE was weakly detected in the iris, ciliary body stroma, and choriocapillaris, but RAGE was hardly detected. Conclusion: AGE is highly accumulated in vascularized intraocular tissues of diabetic eyes, suggesting that AGE accumulation may play an important role in the pathogenesis of diabetic vasculopathy. This study indicates that inhibition of AGE formation may be an important therapeutic strategy for suppressing the progression of diabetic ocular complications.

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Kase, S. , Ishida, S. and Rao, N. (2011) Immunolocalization of advanced glycation end products in human diabetic eyes: an immunohistochemical study. Journal of Diabetes Mellitus, 1, 57-62. doi: 10.4236/jdm.2011.13009.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Yamagishi, S., Nakamura, K., Matsui, T., Ueda, S., Fukami, K. and Okuda, S. (2008) Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: A novel therapeutic strategy for diabetic vascular complications. Expert Opinion on Investigational Drugs, 17, 983-996. doi:10.1517/13543784.17.7.983
[2] Brownlee, M. (2001) Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813-820. doi:10.1038/414813a
[3] Yamagishi, S. and Imaizumi, T. (2005) Diabetic vascular complications: Pathophysiology, biochemical basis and potential therapeutic strategy. Current Pharmaceutical Design, 11, 2279-2299. doi:10.2174/1381612054367300
[4] De La Cruz, J.P., Gonzalez-Correa, J.A., Guerrero, A. and de la Cuesta, F.S. (2004) Pharmacological approach to diabetic retinopathy. Diabetes/Metabolism Research and Reviews, 20, 91-113. doi:10.1002/dmrr.432
[5] Donnelly, R., Emslie-Smith A.M., Gardner I.D. and Morris, A.D. (2000) ABC of arterial and venous disease: Vascular complications of diabetes. British Medical Journal, 320, 1062-1066. doi:10.1136/bmj.320.7241.1062
[6] Yanoff, M. and Fine, B. (2002) Ocular pathology, Fifth Ediyion, Mosby, St. Louis.
[7] Fu, M.X., Requena, J.R., Jenkins, A,J,, Lyons, T.J., Baynes, J.W. and Thorpe, S.R. (1996) The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. The Journal of Biological Chemistry, 271, 9982-9986. doi:10.1074/jbc.271.17.9982
[8] Diamanti-Kandarakis, E., Piperi, C., Patsouris, E., Korkolopoulou, P., Panidis, D., Pawelczyk, L., Papavassiliou, A.G. and Duleba, A.J. (2007) Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochemistry and Cell Biology, 127, 581-589. doi:10.1007/s00418-006-0265-3
[9] Thomas, M.C., Forbes, J.M. and Cooper, M.E. (2005) Advanced glycation end products and diabetic nephropathy. American Journal of Therapeutics, 12, 562-572. doi:10.1097/01.mjt.0000178769.52610.69
[10] Calabrese, V., Mancuso, C., Sapienza, M., Puleo, E., Calafato, S., Cornelius, C., Finocchiaro, M., Mangiameli, A., Di Mauro, M., Stella, A.M. and Castellino, P. (2007) Oxidative stress and cellular stress response in diabetic nephropathy. Cell Stress and Chaperones, 12, 299-306. doi:10.1379/CSC-270.1
[11] Endo, M., Yanagisawa, K., Tsuchida, K., Okamoto, T., Matsushita, T., Higuchi, M., Matsuda, A., Takeuchi, M., Makita, Z. and Koike, T. (2001) Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy. Hormone Metabolism Research, 33, 317-322. doi:10.1055/s-2001-15122
[12] Stitt, A.W., Moore, J.E., Sharkey, J.A., Murphy, G., Simpson, D.A., Bucala, R., Vlassara, H. and Archer D.B. (1998) Advanced glycation end products in vitreous: Structural and functional implications for diabetic vitreopathy. Investigative Ophthalmology & Visual Science, 39, 2517-2523.
[13] Stitt, A.W., Li, Y.M., Gardiner, T.A., Bucala, R., Archer, D.B. and Vlassara, H. (1997) Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats. American Society for Investigative Pathology, 150, 523- 531.
[14] Kaji, Y., Usui, T., Oshika, T., Matsubara, M., Yamashita, H., Araie, M., Murata, T., Ishibashi, T., Nagai, R., Horiuchi, S. and Amano, S. (2000) Advanced glycation end products in diabetic corneas. Investigative Ophthalmology & Visual Science, 41, 362-368.
[15] Amano, S., Kaji, Y., Oshika, T., Oka, T., Machinami, R., Nagai, R. and Horiuchi, S. (2001) Advanced glycation end products in human optic nerve head. British Journal of Ophthalmology, 85, 52-55. doi:10.1136/bjo.85.1.52
[16] Handa, J.T., Verzijl, N., Matsunaga, H., Aotaki-Keen, A., Lutty, G.A., te Koppele, J.M., Miyata, T. and Hjelmeland, L.M. (1999) Increase in the advanced glycation end product pentosidine in Bruch’s membrane with age. Investigative Ophthalmology & Visual Science, 40, 775-779.
[17] Sato, E., Mori, F., Igarashi, S., Abiko, T., Takeda, M., Ishiko, S. and Yoshida, A. (2001) Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy. Diabetes Care, 24, 479-482. doi:10.2337/diacare.24.3.479
[18] Yokoi, M., Yamagishi, S.I., Takeuchi, M., Ohgami, K., Okamoto, T., Saito, W., Muramatsu, M., Imaizumi, T. and Ohno, S. (2005) Elevations of AGE and vascular endothelial growth factor with decreased total antioxidant status in the vitreous fluid of diabetic patients with retinopathy. British Journal of Ophthalmology, 89, 673-675. doi:10.1136/bjo.2004.055053
[19] Jandeleit-Dahm, K. and Cooper, M.E. (2008) The role of AGEs in cardiovascular disease. Current Pharmaceutical Design, 14, 979-986. doi:10.2174/138161208784139684
[20] Watkinson, S. and Seewoodhary, R. (2008) Ocular complications associated with diabetes mellitus. Nursing Standard, 22, 51-57.
[21] Kadoglou, N.P., Daskalopoulou, S.S., Perrea, D. and Liapis, C.D. (2005) Matrix metalloproteinases and diabetic vascular complications. Angiology, 56, 173-189. doi:10.1177/000331970505600208
[22] Goto, H., Mochizuki, M., Yamaki, K., Kotake, S., Usui, M. and Ohno, S. (2007) Epidemiological survey of intraocular inflammation in Japan. Japanese Journal of Ophthalmology, 51, 41-44. doi:10.1007/s10384-006-0383-4
[23] Lappas, M., Permezel, M. and Rice, G.E. (2007) Advanced glycation endproducts mediate pro-inflammatory actions in human gestational tissues via nuclear factor-kappaB and extracellular signal-regulated kinase 1/2. Journal of Endocrinology, 193, 269-277. doi:10.1677/JOE-06-0081
[24] Kitamura, M., Kitaichi, N., Takeuchi, M., Kitamei, H., Namba, K., Yamagishi, S.I., Iwabuchi, K., Onoé and K. Ohno, S. (2005) Decrease in the glyceraldehyde derived advanced glycation end products in the sera of patients with Vogt-Koyanagi-Harada disease. British Journal of Ophthalmology, 89, 1407-1409. doi:10.1136/bjo.2005.072678
[25] Pachydaki, S.I., Tari, S.R., Lee, S.E., Ma, W., Tseng, J.J., Sosunov, A.A., Cataldergirmen, G., Scarmeas, N., Caspersen, C., Chang, S., Schiff, W.M., Schmidt, A.M. and Barile, G.R. (2006) Upregulation of RAGE and its ligands in proliferative retinal disease. Experimental Eye Research, 82, 807-815. doi:10.1016/j.exer.2005.09.022

  
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