Renin-angiotensin and kallikrein-kinin systems in diabetic retinopathy
Abstract
This brief review describes how two complex systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), affect the retina. It emphasizes the important physiological actions of components of these systems, the protective effectiveness of angiotensin I converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in diabetic retinopathy, and suggests as well the therapeutic possibilities for treatment of diabetic retinopathy by selective activation of bradykinin receptors (B1 and B2). The preferred pharmacological target likely would be activation of B1 or B2 receptors.
References
Igić R. Four decades of ocular renin-angiotensin and kallikrein-kinin systems (1977-2017). Exp Eye Res 2018;166:74-83.
Igić R. An exploration of bioactive peptides: My collaboration with Ervin G. Erdös. J Biol Chem 2018; 293:7907-7915.
Ferrao FM, Lara LS, Lowe J. Renin-angiotensin system in the kidney: what is new? World J Nephrol 2014;3 64-76.
Škrbić R, Igić R. Seven decades of angiotensin (1939-2009). Peptides 2009;30;1945-1950.
Igić R, Kojović V. Angiotensin I converting enzyme (kininase II) in ocular tissues. Exp Eye Res 1980;30:299-303.
Igić R, Behnia R. Properties and distribution of angiotensin I converting enzyme. Curr Pharm Des 2003;9: 697-706.
Alhenc-Gelas F, Bouby N, Girolami JP. Kallikrein/K1, kinins, and ACE/kininase II in homeostasis and in disease insight from human and experimental genetic studies, therapeutic implication. Front Med (Lausanne) 2019;6:136. doi: 10.3389/fmed.2019.00136.
Seki T, Miwa I, Nakajima T, Erdös EG. Plasma kallikrein-kinin system in
Pathak M, Wong SS, Dreveny I, Emsley J. Structure of plasma and tissue kallikreins. Thromb Haemost. 2013;110:423-33. doi: 10.1160/TH12-11-0840.
Johnson AR, Skidgel RA, Gafford JT, Erdös EG. Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase (“enkephalinase”). Peptides 1984;5:789-796.
Zhang X, Tan F, Brovkovych V, Zhang Y, Lowry JL, Skidgel RA.
Su JB. Different cross-talk sites between the renin angiotensin and the
Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, et al. Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A. Hypertension 2002;39:976-81.
Ferrario CM, Cheng CP, Varagić J. Angiotensin-(1-7) and the heart. In Angiotensin-(1-7), ed. Santos RAS. Springer, New York, pp.83-104, 2019.
Van Haeringen NJ. The renin-angiotensin system in the human eye. Br J Ophthalmol 1996;80:99-100.
Igić R, Robinson CJG, Erdös EG. Angiotensin I converting enzyme in the
Danser AH, Derkx FH, Admiraal PJ, Deinum J, de Jong PT, Schalekamp MA. Angiotensin levels in the eye. Invest Ophthalmol Vis Sci 1994;35:1008-1018.
Choudhary R, Singh M, Kapoor MS, Singh A, Bodakhe SH. Therapeutic
Metzger R, Franke FE, Bohle RM, Alhenc-Gelas F, Danilov SM. Heterogeneous distribution of angiotensin I-converting enzyme (CD143) in the human and rat vascular systems: vessel, organ and species specificity. Microvasc Res 2011;81:206-15. doi: 10.1016/j.mvr.2010.12.003.
Ward PE, Stewart TA, Hammon KJ, Reynolds RC, Igić R. Angiotensin I converting enzyme (kininase II) in isolated retinal microvessels. Life Sci 1979;24:1419-1424.
Bhat M, Pouliot M, Couture R, Vaucher E. The kallikrein-kinin system in
Igić R. Kallikrein and kininases in ocular tissues. Exp Eye Res 1985;41:117-120.
Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med 2012;366:1227-1239.
Kanda A, Ishida S. (Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy. J Diabetes Investig 2019;10:6-17.
Díaz-Coránguez M, Ramos C, Antonetti DA. The inner blood-retinal barrier: Cellular basis and development. Vision Res 2017;139:123-137. doi: 10.1016/j.visres.2017.05.009.
Erdös EG. In: Advances in pharmacology, edited by Garattini S and Shore PA. Vol. 4, pp. 1-90. New York, Academic Press, 1966.
Wang B, Wang F, Zhang Y, Zhao SH, Zhao WJ, Yan SL, et al. Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2015;3:263-74. doi: 10.1016/S2213-8587(14)70256-6.
Belanger S, Bovenzi V, Cote J, Neugebauer W, Amblard M, Martinez J, et al. Structure-activity relationships of novel peptide agonists of the human bradykinin B2 receptor. Peptides 2009;30:777-787.
Cote J, Savard M, Bovenzi V, Belanger S, Morin J, Neugebauer W, et al. Novel kinin B1 receptor agonists with improved pharmacological profiles. Peptides 2009;30:788-795.
Desposito D, Waecked L, Potier l, Richer C, Roussel R, Rouby N, et al. Kallikrein (K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications. Biol Chem 2016;397:1217-1222.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).