Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular renin-angiotensin system.

J Wagner, A H Jan Danser, F H Derkx, T V de Jong, M Paul, J J Mullins, M A Schalekamp and D Ganten

German Institute for High Blood Pressure Research, University of Heidelberg, Germany.

AIMS/BACKGROUND: All components necessary for the formation of angiotensin II, the biologically active product of the renin-angiotensin system (RAS), have been demonstrated in ocular tissue or vitreous and subretinal fluid. The tissue concentrations of renin were too high to be explained by admixture of blood. This raises the possibility of an intraocular RAS, independent of the RAS in the circulation. METHODS: In the present study, gene expression of RAS components in different parts of enucleated human eyes was investigated as evidence for tissue specific production. RESULTS: By using pooled tissue samples renin mRNA could be detected with the RNAse protection assay in retinal pigment epithelium (RPE) choroid, but not in neural retina or sclera. With reverse transcription polymerase chain reaction (RT-PCR), renin mRNA was detected in individual samples of RPE choroid and neural retina, and not anterior uveal tract or sclera. Angiotensinogen and angiotensin converting enzyme (ACE) gene expression could be demonstrated by RT-PCR in individual RPE choroid and neural retina samples and marginally in sclera samples. CONCLUSIONS: These results support the concept of intraocular synthesis of angiotensin II, independent of renin, angiotensin, and ACE in the circulation. Since gene expression was highest in ocular parts, which are highly vascularised, local angiotensin II may be involved in blood supply and/or pathological vascular processes such as neovascularisation in diabetic retinopathy.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

The renin-angiotensin system in the human eye.

N J Van Haeringen
Br. J. Ophthalmol. 1996 80: 99-100. [PDF]

This article has been cited by other articles:

• Mauer, M., Zinman, B., Gardiner, R., Suissa, S., Sinaiko, A., Strand, T., Drummond, K., Donnelly, S., Goodyer, P., Gubler, M. C., Klein, R. (2009). Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes. NEJM 361: 40-51 [Abstract] [Full Text]  
• Okunuki, Y., Usui, Y., Nagai, N., Kezuka, T., Ishida, S., Takeuchi, M., Goto, H. (2009). Suppression of Experimental Autoimmune Uveitis by Angiotensin II Type 1 Receptor Blocker Telmisartan. IOVS 50: 2255-2261 [Abstract] [Full Text]  
• Striker, G. E., Praddaude, F., Alcazar, O., Cousins, S. W., Marin-Castano, M. E. (2008). Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II. Am. J. Physiol. Cell Physiol. 295: C1633-C1646 [Abstract] [Full Text]  
• Ootaki, C., Yamashita, M., Ootaki, Y., Kamohara, K., Weber, S., Klatte, R. S., Smith, W. A., Massiello, A. L., Emancipator, S. N., Golding, L. A.R., Fukamachi, K. (2008). Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin-Angiotensin System. J. Thorac. Cardiovasc. Surg. 136: 150-158 [Abstract] [Full Text]  
• Vaajanen, A., Vapaatalo, H., Kautiainen, H., Oksala, O. (2008). Angiotensin (1-7) Reduces Intraocular Pressure in the Normotensive Rabbit Eye. IOVS 49: 2557-2562 [Abstract] [Full Text]  
• Veerappan, A., Reid, A. C., Estephan, R., O'Connor, N., Thadani-Mulero, M., Salazar-Rodriguez, M., Levi, R., Silver, R. B. (2008). Mast cell renin and a local renin-angiotensin system in the airway: Role in bronchoconstriction. Proc. Natl. Acad. Sci. USA 105: 1315-1320 [Abstract] [Full Text]  
• Chen, P., Guo, A. M., Edwards, P. A., Trick, G., Scicli, A. G. (2007). Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293: R1619-R1629 [Abstract] [Full Text]  
• Senanayake, P. deS., Drazba, J., Shadrach, K., Milsted, A., Rungger-Brandle, E., Nishiyama, K., Miura, S.-I., Karnik, S., Sears, J. E., Hollyfield, J. G. (2007). Angiotensin II and Its Receptor Subtypes in the Human Retina. IOVS 48: 3301-3311 [Abstract] [Full Text]  
• Kurihara, T., Ozawa, Y., Shinoda, K., Nagai, N., Inoue, M., Oike, Y., Tsubota, K., Ishida, S., Okano, H. (2006). Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1R) Blocker, Telmisartan, via Modulating AT1R and AT2R Signaling in Retinal Inflammation. IOVS 47: 5545-5552 [Abstract] [Full Text]  
• Paul, M., Poyan Mehr, A., Kreutz, R. (2006). Physiology of local Renin-Angiotensin systems.. Physiol. Rev. 86: 747-803 [Abstract] [Full Text]  
• Nagai, N., Oike, Y., Noda, K., Urano, T., Kubota, Y., Ozawa, Y., Shinoda, H., Koto, T., Shinoda, K., Inoue, M., Tsubota, K., Yamashiro, K., Suda, T., Ishida, S. (2005). Suppression of Ocular Inflammation in Endotoxin-Induced Uveitis by Blocking the Angiotensin II Type 1 Receptor. IOVS 46: 2925-2931 [Abstract] [Full Text]  
• Hashizume, K., Mashima, Y., Fumayama, T., Ohtake, Y., Kimura, I., Yoshida, K., Ishikawa, K., Yasuda, N., Fujimaki, T., Asaoka, R., Koga, T., Kanamoto, T., Fukuchi, T., Miyaki, K., The Glaucoma Gene Research Group, (2005). Genetic Polymorphisms in the Angiotensin II Receptor Gene and Their Association with Open-Angle Glaucoma in a Japanese Population. IOVS 46: 1993-2001 [Abstract] [Full Text]  
• Sarlos, S., Wilkinson-Berka, J. L. (2005). The Renin-Angiotensin System and the Developing Retinal Vasculature. IOVS 46: 1069-1077 [Abstract] [Full Text]  
• Yilmaz, M. I., Sonmez, A., Kilic, S., Celik, T., Bingol, N., Pinar, M., Mumcuoglu, T., Ozata, M. (2005). The association of plasma adiponectin levels with hypertensive retinopathy. Eur J Endocrinol 152: 233-240 [Abstract] [Full Text]  
• Silver, R. B., Reid, A. C., Mackins, C. J., Askwith, T., Schaefer, U., Herzlinger, D., Levi, R. (2004). Mast cells: A unique source of renin. Proc. Natl. Acad. Sci. USA 101: 13607-13612 [Abstract] [Full Text]  
• Strain, W D., Chaturvedi, N. (2002). Review: The renin-angiotensin-aldosterone system and the eye in diabetes. Journal of Renin-Angiotensin-Aldosterone System 3: 243-246 [Abstract]  
• Cullinane, A B, Leung, P S, Ortego, J, Coca-Prados, M, Harvey, B J (2002). Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium. Br. J. Ophthalmol. 86: 676-683 [Abstract] [Full Text]  
• Funatsu, H, Yamashita, H, Nakanishi, Y, Hori, S (2002). Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. Br. J. Ophthalmol. 86: 311-315 [Abstract] [Full Text]  
• Drixler, T. A., Rinkes, I. H. M. B., Ritchie, E. D., Treffers, F. W., van Vroonhoven, T. J. M. V., Gebbink, M. F. B. G., Voest, E. E. (2001). Angiostatin Inhibits Pathological but Not Physiological Retinal Angiogenesis. IOVS 42: 3325-3330 [Abstract] [Full Text]  
• Otani, A., Takagi, H., Oh, H., Koyama, S., Honda, Y. (2001). Angiotensin II Induces Expression of the Tie2 Receptor Ligand, Angiopoietin-2, in Bovine Retinal Endothelial Cells. Diabetes 50: 867-875 [Abstract] [Full Text]  
• Moravski, C. J., Kelly, D. J., Cooper, M. E., Gilbert, R. E., Bertram, J. F., Shahinfar, S., Skinner, S. L., Wilkinson-Berka, J. L. (2000). Retinal Neovascularization Is Prevented by Blockade of the Renin-Angiotensin System. Hypertension 36: 1099-1104 [Abstract] [Full Text]  
• Uckaya, G., Ozata, M., Sonmez, A., Kinalp, C., Eyileten, T., Bingol, N., Koc, B., Kocabalkan, F., Ozdemir, I. C. (2000). Is Leptin Associated with Hypertensive Retinopathy?. J. Clin. Endocrinol. Metab. 85: 683-687 [Abstract] [Full Text]  
• Methot, D., Silversides, D. W., Reudelhuber, T. L. (1999). In Vivo Enzymatic Assay Reveals Catalytic Activity of the Human Renin Precursor in Tissues. Circ. Res. 84: 1067-1072 [Abstract] [Full Text]  
• Yan, Y., Chen, R., Pitarresi, T., Sigmund, C. D., Gross, K. W., Sealey, J. E., Laragh, J. H., Catanzaro, D. F. (1998). Kidney Is the Only Source of Human Plasma Renin in 45-kb Human Renin Transgenic Mice. Circ. Res. 83: 1279-1288 [Abstract] [Full Text]  
• Mäkimattila, S., Summanen, P., Matinlauri, I., Mäntysaari, M., Schlenzka, A., Aalto, M., Irjala, K., Yki-Järvinen, H. (1998). Serum total renin, an independent marker of the activity and severity of retinopathy in patients with IDDM. Br. J. Ophthalmol. 82: 939-944 [Abstract] [Full Text]  
• BUCKLEY, C. H, HADOKE, P. W F, O'BRIEN, C. J (1997). Use of isolated ocular arteries in vitro to define the pathology of vascular changes in glaucoma. Br. J. Ophthalmol. 81: 599-607 [Full Text]