Systemic and periocular deliveries of plasminogen kringle 5 reduce vascular leakage in rat models of oxygen-induced retinopathy and diabetes.
OBJECTIVE
Increased retinal vascular permeability is a common complication of diabetes and a major cause of vision loss in diabetic patients. The current study is to determine the effect of plasminogen kringle 5 (K5) on vascular leakage via systemic and periocular deliveries.


METHODS
Oxygen-induced retinopathy (OIR) was generated by exposing newborn rats to 75% oxygen. Diabetes was induced in adult rats by injection of streptozotocin (STZ). Retinal vascular permeability was measured by the Evans blue-albumin leakage method.


RESULTS
Subcutaneous, intraperitoneal, subconjunctival, and retrobulbar injections and topical eyedrop application of K5 significantly reduced retinal vascular permeability in both the OIR and STZ-diabetic rat models. Compared with the periocular deliveries, systemic administration requires higher doses of K5. K5 deliveries downregulated VEGF expression in the retina.


CONCLUSIONS
K5 can reduce retinal vascular permeability through systemic and periocular deliveries. These delivery routes of K5 have therapeutic potential in the treatment of vascular leakage.
Zhang
Sarah X
SX
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Sima
Jing
J
Wang
Joshua J
JJ
Shao
Chunkui
C
Fant
James
J
Ma
Jian-Xing
JX
D000818:Animals; D000831:Animals, Newborn; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004333:Drug Administration Routes; D007124:Immunoenzyme Techniques; D010100:Oxygen / Q000633:toxicity; D010446:Peptide Fragments / Q000008:administration & dosage*; D010958:Plasminogen / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000378:metabolism; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C491499:plasminogen kringle 5; D010958:Plasminogen; D010100:Oxygen