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Impressum
Intravitreal injection of Arg-Gly-Asp (RGD) peptide facilitates surgical creation of a posterior vitreous detachment in pig and rabbit model
1,3Meyer C. H., 1Oliveira L. B., 1Kumar J., 1Tatbayashi M., 1,2Toth C. A., 1McCuen II B. W.
1Department of Ophthalmology, Duke University Medical Center, Durham, NC; 2Departments of Biomedical Engineering, Duke University, Durham, NC; 3Universitätsaugenklinik, Phillips-Universität, Marburg
Purpose: To evaluate the efficacy of intravitreal injection of
Arg-Gly-Asp (RGD) peptide in facilitating the separation of the posterior
cortical vitreous from the retinal surface during vitrectomy in two experimental
animal models.
Methods: Pig group: 8 animals received 1.0 mg active RGD-TP
peptide into the midvitreous of one eye and PBS into the fellow eye as
a control. At varying time intervals (2h, 6h, 12h or 24 h) a vitrector
applied a mechanical aspiration of 25mmHg near the optic disc, to induce
a PVD. Rabbit group: In a double blind fashion 6 animals received
an intravitreal injection of 1mg RGD-TP peptide into one eye and inactive
RGD-SP peptide into the fellow eye. Mechanical aspiration to induce a
PVD was applied in the same manner. Intraoperative observation, indirect
ophthalmoscopy and kinetic ultrasound were used to evaluate and classify
the status of the posterior vitreous: Total PVD without evidence of retinal
traction; total PVD with evidence of retinal traction; partial PVD; and
no PVD. Scanning electron microscopy (SEM) and immunohistochemistry were
performed in two rabbits. In addition, two animals were followed for 5
days to study the long-term effects of active and inactive RGD.
Results: Pig-group: 6 out of 9 eyes treated with RGD-TP
showed a complete PVD without signs of retinal traction >/= 6h after
injection. All control eyes showed either no PVD or PVD with retinal traction,
none had a complete PVD. Rabbit group: In 6 out of 8 eye treated
with RGD-TP a higher incidence of PVD was observed when compared to the
control eye (p=0.01). Ultrasound determined a total number of detached
quadrants in the treatment group of 25, compared to 7 in the control eyes.
SEM confirmed the PVD in selected eyes. No evidence of retina cell apoptosis
was found in either RDG-TP or RGD-SP treated eyes. Eyes treated with RGD-TP
developed a mild vascular exudation followed by a vitritis about 4 to
6 hours after injection. This inflammatory reaction progressively increased
throughout 24 hours and spontaneously resolved between 2 to 5 days. No
inflammation was seen in the control eyes.
Conclusion: The preliminary data of these two experimental animal
models demonstrated that the intravitreal injection of RGD-TP peptide
can facilitate a PVD and may be a new competitive approach for pharmacological
vitreolysis. (Patent file No.1929) CR: none. Support: NIH Grant EY-11498,
NEI Core Grant P30EY05722, Foundation Fighting Blindness, Adler Foundation,
Research to Prevent Blindness (RPB)