Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy.
Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin-kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies.
Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA. bolimark@umich.edu.
Mark T
MT
Bolinger
Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA. dantonet@umich.edu.
David A
DA
Antonetti
D000068879:Adalimumab / Q000627:therapeutic use*; D000818:Animals; D000068258:Bevacizumab / Q000627:therapeutic use; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D004358:Drug Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C511194:ecallantide; D007610:Kallikreins; D000068879:Adalimumab
TNF-α; VEGF; angiopoietin; blood retinal barrier; corticosteroid; cytokine; diabetic macular edema; diabetic retinopathy; kinin-kallikrein system; renin-angiotensin system; vitreomacular adhesion