Esther S. Kim

Pharmacokinetics of intraocular drug delivery of Oregon green 488-labeled triamcinolone by subtenon injection using ocular fluorophotometry in rabbit eyes.

PURPOSE To evaluate the transscleral delivery of Oregon Green-labeled triamcinolone acetonide (OGTA) into the eye. METHODS Ex vivo experiments were performed on rabbit sclera in a Lucite block perfusion chamber. Two hundred microliters OGTA (5 mg/mL) was placed on the outer surface of the sclera for 24 hours. The exposed sclera was divided into two pieces; one half for a washout of OGTA and the other for histology. The concentration of OGTA that diffused through the sclera (n = 6) was measured by fluorometry. Two hundred microliters of OGTA (5 mg/mL) was also injected subtenon into live (n = 6) and euthanatized rabbits (n = 3). Intraocular OGTA concentrations were measured by ocular fluorophotometry. RESULTS The permeability constant for the transscleral diffusion (K(trans)) of OGTA was 1.12 x 10(-7) +/- 0.08 cm/s (n = 8) during the steady state perfusion. Washout tests showed higher OGTA concentration in the sclera exposed to OGTA for 4 hours than in that exposed for 1 hour. Fluorescent microscopy showed OGTA fluorescence throughout the exposed sclera, as evidence of scleral penetration of OGTA. The maximum OGTA concentration in the retina/choroid after subtenon injection was 25.77 +/- 10.26 ng/mL in the live rabbit at 3 hours and 84.68 +/- 21.04 ng/mL in the euthanatized rabbits at 8 hours. CONCLUSIONS OGTA is capable of diffusing across isolated rabbit sclera ex vivo and into the retina/choroid via transscleral diffusion from a subtenon depot in vivo. Conjunctival and choroidal circulation decreased the drug delivery of OGTA.

Development of Bile Acids as Anti-Apoptotic and Neuroprotective Agents in Treatment of Ocular Disease

The hydrophilic bile acids ursodeoxycholic acid and tauroursodeoxycholic acid are approved by regulatory bodies of many countries for treatment of gallstones and cirrhosis. Delivery is by oral administration and side effects are minimal. This chapter reviews evidence demonstrating that systemic treatment with the two compounds is protective in models of neuronal and retinal degeneration and injury. Variability in the regulation of circulating bile acids suggests a need to explore local delivery as a treatment modality. Our initial experiments testing in vivo intraocular injections and in vitro transscleral permeability indicate that this is feasible and efficacious.