Choroidal neovascularization (CNV) represents the most common cause of severe vision loss in patients with age-related macular degeneration (AMD). It is also the most common cause of legal blindness in the United States in patients over the age of 60. Therefore, the study of the diagnosis, prevention and treatment of this condition would have a major impact on the public health. The laboratory is heavily involved in drug development for the treatment of neovascular AMD. These efforts are within the realm of drug delivery and drug formulation development. Within drug delivery, the laboratory is focusing on the use of sustained implant technology. One important aspect of this work is focusing on the ability of drugs to cross the scleral and allow for extraocular placement of these devices. Published work has reported on our observations that physiologic rather than physical barriers appear to limit drug penetration into the eye. Using a gadolinium implant, work in both alive and dead rabbits showed a dramatic difference in ocular drug penetration highlighting the importance of these physiologic barriers. In a further extension of this work in rabbits, various techniques to alter these physiologic barriers including cryotherapy to reduce choroidal blood flow and removal of conjunctival tissue to alter choroidal vascular and lymphatic elimination routes demonstrated the importance of these physiologic barriers. On-going work is focused on a more precise identification and manipulation of these barriers. Focusing on the need for improvements in anti-angiogenic agents and modes of delivery, work is continuing on the sustained drug delivery of two integrin antagonists, EMD 0587 and a short peptide, C16Y, both of which have been shown in the laboratory to have anti-angiogenic effects in a laser-induced model of CNV.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000432-02
Application #
7141781
Study Section
(DIR)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kim, Hyuncheol; Csaky, Karl G; Gravlin, Luisa et al. (2006) Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration. Retina 26:523-30
Gilger, Brian C; Salmon, Jacklyn H; Wilkie, David A et al. (2006) A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci 47:2596-605
Kim, Hyuncheol; Csaky, Karl G; Chan, Chi-Chao et al. (2006) The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res 82:760-6
Cruysberg, Lars P J; Franklin, Alan J; Sanders, Jason et al. (2005) Effective transscleral delivery of two retinal anti-angiogenic molecules: carboxyamido-triazole (CAI) and 2-methoxyestradiol (2ME2). Retina 25:1022-31
Kim, Hyuncheol; Csaky, Karl G; Gilger, Brian C et al. (2005) Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease. Invest Ophthalmol Vis Sci 46:655-62
Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger et al. (2005) Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging. Ann Biomed Eng 33:150-64
Kim, Hyuncheol; Robinson, Michael R; Lizak, Martin J et al. (2004) Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging. Invest Ophthalmol Vis Sci 45:2722-31