title: Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis in the Pathogenesis of Diabetic Retinopathy.
abstract: Diabetic retinopathy (DR) is a major diabetes complication and the leading cause for vision loss and blindness in the adult human population. Diabetes, being an endocrinological disorder dysregulates a number of hormonal systems including the renin angiotensin system (RAS), which thereby may damage both vascular and neuronal cells in the retina. Angiotensin II (Ang II), an active component of the RAS is increased in diabetic retina, and may play a significant role in neurovascular damage leading to the progression of DR. In this review article, we highlight the role of Ang II in the pathogenesis of retinal damage in diabetes and discuss a newly identified mechanism involving tissue chymase and angiotensin-(1-12) [Ang-(1-12)] pathways. We also discuss the therapeutic effects of potential RAS inhibitors targeting blockade of cellular Ang II formation to prevent/ protect the retinal damage. Thus, a better understanding of Ang II formation pathways in the diabetic retina will elucidate early molecular mechanism of vision loss. These concepts may provide a novel strategy for preventing and/or treating diabetic retinopathy, a leading cause of blindness worldwide.
authors.affiliation: Department of Biochemistry, College of Science, King Saud, University, Riyadh 11451. Saudi Arabia.
authors.forename: Mohammad Shamsul
authors.initials: MS
authors.lastname: Ola
authors.affiliation: Department of Biochemistry, College of Science, King Saud, University, Riyadh 11451. Saudi Arabia.
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Alhomida
authors.affiliation: Department of General Surgery, Wake Forest University Health Science, Winston-Salem, NC 27157. United States.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.affiliation: Department of General Surgery, Wake Forest University Health Science, Winston-Salem, NC 27157. United States.
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D053818:Chymases / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C000610416:angiotensin-(1-12), human; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D053818:Chymases
keywords: Angiotensin II; chymase; diabetic retinopathy; neurodegeneration; oxidative stress; renin-angiotensin
  system; retina