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Q. Zhang, N. Michaud, S. Bennett, B. Uygun, M. L. Yarmush, M. A. Latina; Pilot Study of Laser Assisted Therapeutic Agent Delivery Into Retina and Subretinal Space. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5972.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the possibility of selectively delivering drugs with high molecular weight into the retinal and subretinal space, based on selective pulsed laser treatment of the Retinal Pigment Epithelium (RPE).
6 Dutch Belted rabbits were irradiated with a pulsed dye laser (Palomar 3010; 590nm, 1µs, 1mm dia ) and a Q-switched Nd:Yag laser (Selecta II, Lumenis; 532 nm, 3ns, 400µm dia). Dose studies were performed to determine the threshold laser energies for selective RPE targeting. Following selective laser treatment of the RPE, drug delivery studies, simulated by intravenous delivery of fluorescein isothiocyanate labeled dextrans (FITC-dextran) with 10K and 40K molecular weight, were conducted. Ophthalmoscopic examination, Fluoresein Angiography, Optical Coherence Tomography (Spectralis, Heidelberg Engineering) and histology (1 µm sections) were performed to detect the presence of the FITC-dextran in the retina and to evaluate structural alterations of the retina and the RPE. Animals were examined immediately and up to 5 weeks post treatment.
Selective targeting of RPE can be achieved at about 0.5mJ (64mJ/cm2) for the dye laser and 10µJ (8 mJ/cm2) for the Nd:Yag laser, where the lesion is ophthalmoscopically invisible and angiographically visible. After administration of FITC-dextran with 10K molecular weight, angiography showed positive leakage within 2 minutes post-injection , and for 40K Dextran within 40minutes, localized to the treatment areas. The RPE barrier was re-established within two weeks as demonstrated by negative leakage using routine fluorescein angiography. Histology at 2 days post-treatment shows disruption of the RPE localized to the treated areas which is greater with the Nd:YAG than the dye laser, without gross damage to the neural retina. By 5 weeks post treatment there is mild RPE pigment clumping only at the treated areas, the overlying layers, including the photo receptor layer, were intact.
These results indicate that large molecular weight substances can be effectively delivered across the RPE barrier following selective treatment of RPE, with preservation of the overlying neural retina. The RPE barrier is re-established later. This suggests a novel technique for selectively delivering large molecular weight drugs across the RPE barrier into the retinal and subretinal space, which may be useful for the treatment of retinal diseases.
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