Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1996 Feb;80(2):159–163. doi: 10.1136/bjo.80.2.159

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 1, A H Jan Danser 1, F H Derkx 1, T V de Jong 1, M Paul 1, J J Mullins 1, M A Schalekamp 1, D Ganten 1
PMCID: PMC505409  PMID: 8814748

Abstract

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.

Full text

PDF
159

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ariza A., Fernandez L. A., Inagami T., Kim J. H., Manuelidis E. E. Renin in glioblastoma multiforme and its role in neovascularization. Am J Clin Pathol. 1988 Oct;90(4):437–441. doi: 10.1093/ajcp/90.4.437. [DOI] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Campbell D. J. Circulating and tissue angiotensin systems. J Clin Invest. 1987 Jan;79(1):1–6. doi: 10.1172/JCI112768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chai S. Y., Mendelsohn F. A., Paxinos G. Angiotensin converting enzyme in rat brain visualized by quantitative in vitro autoradiography. Neuroscience. 1987 Feb;20(2):615–627. doi: 10.1016/0306-4522(87)90114-x. [DOI] [PubMed] [Google Scholar]
  5. Constad W. H., Fiore P., Samson C., Cinotti A. A. Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open-angle glaucoma. Am J Ophthalmol. 1988 Jun 15;105(6):674–677. doi: 10.1016/0002-9394(88)90063-3. [DOI] [PubMed] [Google Scholar]
  6. Cunha-Vaz J., Faria de Abreu J. R., Campos A. J. Early breakdown of the blood-retinal barrier in diabetes. Br J Ophthalmol. 1975 Nov;59(11):649–656. doi: 10.1136/bjo.59.11.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Danser A. H., Derkx F. H., Admiraal P. J., Deinum J., de Jong P. T., Schalekamp M. A. Angiotensin levels in the eye. Invest Ophthalmol Vis Sci. 1994 Mar;35(3):1008–1018. [PubMed] [Google Scholar]
  8. Danser A. H., van den Dorpel M. A., Deinum J., Derkx F. H., Franken A. A., Peperkamp E., de Jong P. T., Schalekamp M. A. Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. J Clin Endocrinol Metab. 1989 Jan;68(1):160–167. doi: 10.1210/jcem-68-1-160. [DOI] [PubMed] [Google Scholar]
  9. Deinum J., Derkx F. H., Danser A. H., Schalekamp M. A. Identification and quantification of renin and prorenin in the bovine eye. Endocrinology. 1990 Mar;126(3):1673–1682. doi: 10.1210/endo-126-3-1673. [DOI] [PubMed] [Google Scholar]
  10. Fernandez L. A., Twickler J., Mead A. Neovascularization produced by angiotensin II. J Lab Clin Med. 1985 Feb;105(2):141–145. [PubMed] [Google Scholar]
  11. Ferrari-Dileo G., Davis E. B., Anderson D. R. Angiotensin binding sites in bovine and human retinal blood vessels. Invest Ophthalmol Vis Sci. 1987 Nov;28(11):1747–1751. [PubMed] [Google Scholar]
  12. Ferrari-Dileo G., Ryan J. W., Rockwood E. J., Davis E. B., Anderson D. R. Angiotensin-converting enzyme in bovine, feline, and human ocular tissues. Invest Ophthalmol Vis Sci. 1988 Jun;29(6):876–881. [PubMed] [Google Scholar]
  13. Franken A. A., Derkx F. H., Man in't Veld A. J., Hop W. C., van Rens G. H., Peperkamp E., de Jong P. T., Schalekamp M. A. High plasma prorenin in diabetes mellitus and its correlation with some complications. J Clin Endocrinol Metab. 1990 Oct;71(4):1008–1015. doi: 10.1210/jcem-71-4-1008. [DOI] [PubMed] [Google Scholar]
  14. Goedert M., Spillantini M. G., Potier M. C., Ulrich J., Crowther R. A. Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J. 1989 Feb;8(2):393–399. doi: 10.1002/j.1460-2075.1989.tb03390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hermann K., Raizada M. K., Sumners C., Phillips M. I. Presence of renin in primary neuronal and glial cells from rat brain. Brain Res. 1987 Dec 29;437(2):205–213. doi: 10.1016/0006-8993(87)91637-4. [DOI] [PubMed] [Google Scholar]
  16. Hirsch A. T., Talsness C. E., Schunkert H., Paul M., Dzau V. J. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res. 1991 Aug;69(2):475–482. doi: 10.1161/01.res.69.2.475. [DOI] [PubMed] [Google Scholar]
  17. Kawasaki E. S., Clark S. S., Coyne M. Y., Smith S. D., Champlin R., Witte O. N., McCormick F. P. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698–5702. doi: 10.1073/pnas.85.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kumar A., Rassoli A., Raizada M. K. Angiotensinogen gene expression in neuronal and glial cells in primary cultures of rat brain. J Neurosci Res. 1988 Mar;19(3):287–290. doi: 10.1002/jnr.490190302. [DOI] [PubMed] [Google Scholar]
  19. Kumar A., Rassoli A., Raizada M. K. Angiotensinogen gene expression in neuronal and glial cells in primary cultures of rat brain. J Neurosci Res. 1988 Mar;19(3):287–290. doi: 10.1002/jnr.490190302. [DOI] [PubMed] [Google Scholar]
  20. Luetscher J. A., Kraemer F. B., Wilson D. M., Schwartz H. C., Bryer-Ash M. Increased plasma inactive renin in diabetes mellitus. A marker of microvascular complications. N Engl J Med. 1985 May 30;312(22):1412–1417. doi: 10.1056/NEJM198505303122202. [DOI] [PubMed] [Google Scholar]
  21. Naftilan A. J., Zuo W. M., Inglefinger J., Ryan T. J., Jr, Pratt R. E., Dzau V. J. Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall. J Clin Invest. 1991 Apr;87(4):1300–1311. doi: 10.1172/JCI115133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Paul M., Printz M. P., Harms E., Unger T., Lang R. E., Ganten D. Localization of renin (EC 3.4.23) and converting enzyme (EC 3.4.15.1) in nerve endings of rat brain. Brain Res. 1985 May 20;334(2):315–324. doi: 10.1016/0006-8993(85)90224-0. [DOI] [PubMed] [Google Scholar]
  23. Paul M., Wagner J., Dzau V. J. Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction. J Clin Invest. 1993 May;91(5):2058–2064. doi: 10.1172/JCI116428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rockwood E. J., Fantes F., Davis E. B., Anderson D. R. The response of retinal vasculature to angiotensin. Invest Ophthalmol Vis Sci. 1987 Apr;28(4):676–682. [PubMed] [Google Scholar]
  25. Sramek S. J., Wallow I. H., Day R. P., Ehrlich E. N. Ocular renin-angiotensin: immunohistochemical evidence for the presence of prorenin in eye tissue. Invest Ophthalmol Vis Sci. 1988 Nov;29(11):1749–1752. [PubMed] [Google Scholar]
  26. Sramek S. J., Wallow I. H., Tewksbury D. A., Brandt C. R., Poulsen G. L. An ocular renin-angiotensin system. Immunohistochemistry of angiotensinogen. Invest Ophthalmol Vis Sci. 1992 Apr;33(5):1627–1632. [PubMed] [Google Scholar]
  27. Weinreb R. N., Sandman R., Ryder M. I., Friberg T. R. Angiotensin-converting enzyme activity in human aqueous humor. Arch Ophthalmol. 1985 Jan;103(1):34–36. doi: 10.1001/archopht.1985.01050010038013. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES