NorLeu3A(1-7) Accelerates Clear Corneal Full Thickness Wound Healing.
OBJECTIVE
We evaluated the effect of the renin angiotensin system (RAS) peptide NorLeu3-Angiotensin (1-7) (NLE) formulated in a viscoelastic gel (USB004) on the healing of full-thickness corneal injuries.


METHODS
Dutch pigmented rabbits received conjunctival administration of 0.3% USB004, 0.03% USB004, or vehicle-control to healthy and full-thickness injured eyes administered once daily for 28 consecutive days. Safety was evaluated using IOP measurement, slit-lamp examination, and confocal microscopy. Evaluations for both efficacy studies included an oblique light examination, modified Seidel test (Seidel test with gentle ocular pressure) as well as during elevated IOP test, confocal microscopy imaging, and histologic analysis.


RESULTS
Application of 0.3% USB004, 0.03% USB004, and vehicle-control was safe in healthy and incised eyes. Further, application of 0.3% and 0.03% USB004 following full-thickness corneal incision resulted in a 2-fold acceleration of resolution of edema and inflammation, reduction in duration of wound leakage on a modified Seidel test (Seidel test with gentle ocular pressure) as well as during elevated IOP test, and healing with near normal architecture without evidence of fibrosis and angiogenesis when compared to vehicle-control animals.


CONCLUSIONS
Topical ocular application of 0.3% and 0.03% USB004 promotes full-thickness cornea wound healing without the evidence of fibrosis and angiogenesis. Further studies are warranted to determine the cornea-specific mechanism of action(s) that promotes regeneration leading to clear corneal healing.
USC Eye Institute, University of Southern California, Los Angeles, California, United States.
Walid F
WF
Abdallah
Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California, United States 3Keck School of Medicine, University of Southern California, Los Angeles, California, United States 4Institute for.
Stan G
SG
Louie
USC Eye Institute, University of Southern California, Los Angeles, California, United States 4Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States.
Yi
Y
Zhang
Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California, United States.
Kathleen E
KE
Rodgers
US-Biotest, San Luis Obispo, California, United States.
Emily
E
Sivok
US-Biotest, San Luis Obispo, California, United States.
Gere
G
S diZerega
USC Eye Institute, University of Southern California, Los Angeles, California, United States 3Keck School of Medicine, University of Southern California, Los Angeles, California, United States 4Institute for Biomedical Therapeutics, University of Southern.
Mark S
MS
Humayun
D060433:Administration, Ophthalmic; D000804:Angiotensin II / Q000627:therapeutic use*; D000818:Animals; D002921:Cicatrix / Q000517:prevention & control; D003315:Cornea / Q000648:ultrastructure; D065306:Corneal Injuries / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000627:therapeutic use*; D011817:Rabbits; D066167:Slit Lamp; D014945:Wound Healing / Q000187:drug effects*
D010446:Peptide Fragments; C473306:norLeu3-A(1-7); D000804:Angiotensin II