TY - JOUR
T1 - Is the arginase pathway a novel therapeutic avenue for diabetic retinopathy?
AU - Shosha, Esraa
AU - Fouda, Abdelrahman Y.
AU - Narayanan, S. Priya
AU - Caldwell, R. William
AU - Caldwell, Ruth B.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - Diabetic retinopathy (DR) is the leading cause of blindness in working age Americans. Clinicians diagnose DR based on its characteristic vascular pathology, which is evident upon clinical exam. However, extensive research has shown that diabetes causes significant neurovascular dysfunction prior to the development of clinically apparent vascular damage. While laser photocoagulation and/or anti-vascular endothelial growth factor (VEGF) therapies are often effective for limiting the late-stage vascular pathology, we still do not have an effective treatment to limit the neurovascular dysfunction or promote repair during the early stages of DR. This review addresses the role of arginase as a mediator of retinal neurovascular injury and therapeutic target for early stage DR. Arginase is the ureohydrolase enzyme that catalyzes the production of L-ornithine and urea from L-arginine. Arginase upregulation has been associated with inflammation, oxidative stress, and peripheral vascular dysfunction in models of both types of diabetes. The arginase enzyme has been identified as a therapeutic target in cardiovascular disease and central nervous system disease including stroke and ischemic retinopathies. Here, we discuss and review the literature on arginase-induced retinal neurovascular dysfunction in models of DR. We also speculate on the therapeutic potential of arginase in DR and its related underlying mechanisms.
AB - Diabetic retinopathy (DR) is the leading cause of blindness in working age Americans. Clinicians diagnose DR based on its characteristic vascular pathology, which is evident upon clinical exam. However, extensive research has shown that diabetes causes significant neurovascular dysfunction prior to the development of clinically apparent vascular damage. While laser photocoagulation and/or anti-vascular endothelial growth factor (VEGF) therapies are often effective for limiting the late-stage vascular pathology, we still do not have an effective treatment to limit the neurovascular dysfunction or promote repair during the early stages of DR. This review addresses the role of arginase as a mediator of retinal neurovascular injury and therapeutic target for early stage DR. Arginase is the ureohydrolase enzyme that catalyzes the production of L-ornithine and urea from L-arginine. Arginase upregulation has been associated with inflammation, oxidative stress, and peripheral vascular dysfunction in models of both types of diabetes. The arginase enzyme has been identified as a therapeutic target in cardiovascular disease and central nervous system disease including stroke and ischemic retinopathies. Here, we discuss and review the literature on arginase-induced retinal neurovascular dysfunction in models of DR. We also speculate on the therapeutic potential of arginase in DR and its related underlying mechanisms.
KW - Arginase
KW - Diabetic retinopathy
KW - Neurovascular injury
KW - Therapy
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U2 - 10.3390/jcm9020425
DO - 10.3390/jcm9020425
M3 - Review article
AN - SCOPUS:85087011639
SN - 2077-0383
VL - 9
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 2
M1 - 425
ER -