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Jeffrey L. Haddox, Roswell R. Pfister, Charnell I. Sommers, J. Edward Blalock, Matteo Villain; Inhibitory Effect of a Complementary Peptide on Ulceration in the Alkali-Injured Rabbit Cornea. Invest. Ophthalmol. Vis. Sci. 2001;42(12):2769-2775.
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purpose. Two tripeptide chemoattractants, acetyl-proline-glycine-proline
(Ac-PGP) and methyl-proline-glycine-proline (Me-PGP), are the primary
triggers for early neutrophil invasion into the alkali-injured cornea.
In the present study the effectiveness of a complementary peptide
designed to inhibit the PGP chemoattractants
(arginine-threonine-arginine [RTR] tetrameric peptide) and an apo A-1
mimicking peptide (5F) was investigated in the alkali-injured rabbit
methods. (L)-RTR tetramer, (D)-RTR tetramer, and 5F were tested in vitro for
their effects on neutrophil polarization. Synthetic 5F was also tested
in vitro for its effect on the neutrophil respiratory burst. In the
alkali-injured rabbit eye model, the right corneas of 48 rabbits were
exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly
assigned to each of three groups: phosphate-buffered saline (PBS)
control; 800 μM RTR (dextrorotatory) tetramer in PBS alternating each
hour with 1.5 mM RTR (levorotatory) tetramer in PBS; and 12 μM 5F in
PBS. One topical drop of each substance was administered hourly (14
times per day) for 33 days. The experiment was continued until day 42
with no additional drops administered.
results. (L)-RTR tetramer and (D)-RTR tetramer inhibited neutrophil polarization
activated by the PGP chemoattractants in vitro. Synthetic 5F did not
inhibit neutrophil polarization in the presence of Ac-PGP or the
respiratory burst of neutrophils in the presence of a metabolic
stimulant derived from alkali-degraded corneas. During the entire
animal experiment, statistically fewer ulcers occurred in the RTR
tetramer group than in the PBS control group (43.8% vs. 87.5%, P = 0.0046). The frequency of ulceration in the 5F
group (68.8%) was not significantly different from the PBS control
conclusions. The reduction in the frequency of corneal ulceration by the RTR
tetramer possibly resulted from its complementary binding to Ac-PGP and
Me-PGP in the cornea shortly after alkali injury, leading to a
reduction in the early and late infiltration of neutrophils. RTR
tetramer appears to hold enough promise to warrant additional study as
a therapeutic drug for the alkali-injured eye.
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