Laser-triggered, lipsome-encapsulated fluorescent dyes can be used as a tracer in the eye. Fluorescein is widely used in ophthalmic diagnosis, but it must be applied topically or injected intravenously, resulting in diffuse spread of dye through the retinal circulation along with high levels of background fluorescence in the choroid. Carboxyfluorescein and calcein, dyes similar to fluorescein, can be encapsulated in liposomes at high concentrations (100 mM). At such elevated concentrations, the fluorescence is quenched, but when the dye is released from the liposome, it is diluted and fluoresces intensely. Liposomes containing these fluorescent dyes can be injected intravenously and once in the circulation, can be trigged to release their contents by a localized pulse of light from a laser. The dye converts the laser into heat, which raises the temperature of the liposomal envelope, lyses the liposome, and releases the dye. The ability to control location, timing, and repetition of dye release would allow local flow patterns to be visualized without the background of the underlying choroidal circulation or adjacent vessel networks. The system will make assessment of localized perfusion defects possible. The creation of a better defined wavefront, achieved with the generation of a bolus, opens the way for quantitative measurement of flow. By controlling the time between the release of the dye from the liposomes and the time of recording, we have been able in preliminary studies to measure the velocity of blood in vitro, as well as in the retinal vessels of rabbits and monkeys. Moreover, the possibility of repeating the procedure allows refinement of alignment and focusing of the camera, thereby optimizing the quality of the photographs. Additionally, measurements can be performed before and after induced changes of physiologic conditions (i.e., oxygen or nitrogen breathing, exposure to light or pharmacological agents). The system offers the control of time, location, and repetition of delivery, which potentially will be useful in a number of therapeutic applications as well.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008137-03
Application #
3265322
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-05-01
Project End
1993-12-31
Budget Start
1991-05-01
Budget End
1993-12-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Khoobehi, B; Peyman, G A (1999) Fluorescent labeling of blood cells for evaluation of retinal and choroidal circulation. Ophthalmic Surg Lasers 30:140-5
Peyman, G A; Khoobehi, B; Moshfeghi, A et al. (1998) Blood velocity in an experimental iris tumor. Ophthalmic Surg Lasers 29:506-9
Peyman, G A; Khoobehi, B; Moshfeghi, A et al. (1998) Reversal of blood flow in experimental branch retinal vein occlusion. Ophthalmic Surg Lasers 29:595-7
Moshfeghi, D M; Peyman, G A; Moshfeghi, A A et al. (1998) Ocular vascular thrombosis following tin ethyl etiopurpurin (SnET2) photodynamic therapy: time dependencies. Ophthalmic Surg Lasers 29:663-8
Peyman, G A; Moshfeghi, D M; Moshfeghi, A et al. (1997) Photodynamic therapy for choriocapillaris using tin ethyl etiopurpurin (SnET2). Ophthalmic Surg Lasers 28:409-17
Khoobehi, B; Shoelson, B; Zhang, Y Z et al. (1997) Fluorescent microsphere imaging: a particle-tracking approach to the hemodynamic assessment of the retina and choroid. Ophthalmic Surg Lasers 28:937-47
Peyman, G A; Moshfeghi, D M; Moshfeghi, A A et al. (1996) Fluorescent vesicle angiography with sodium fluorescein and indocyanine green. Ophthalmic Surg Lasers 27:279-84
Peyman, G A; Khoobehi, B; Shaibani, S et al. (1996) A fluorescent vesicle system for the measurement of blood velocity in the choroidal vessels. Ophthalmic Surg Lasers 27:459-66
Kizhakkethara, I; Li, X; el-Sayed, S et al. (1995) Noninvasive monitoring of intraocular pharmacokinetics of daunorubicin using fluorophotometry. Int Ophthalmol 19:363-7
Golshani, M R; Khoobehi, B; Peyman, G A et al. (1994) Calcein fluorophotometry in streptozocin-induced diabetic rats. Ophthalmic Surg 25:526-31

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