Subconjunctival Delivery of a Neuroprotectant using Fibrin Sealant

Abstract

Purpose: : To determine whether subconjunctival injection of tauroursodeoxycholic acid (TUDCA) mixed in fibrin sealant results in tissue concentrations previously shown to be protective in retinal degeneration models.

Methods: : 50 ul of TUDCA (52 mg/ml) in fibrin sealant was injected into the subconjunctival space of one eye of each of 20 rats. The other eye was injected with fibrin sealant alone. Other rats were injected i.p. with 500 mg/kg TUDCA every 3 days for two weeks, a proven protective dosing regimen. Total UDCA levels were assessed by gas chromatography.

Results: : Total UDCA in retinas from eyes injected with fibrin sealant/TUDCA was 16.7 nmol/g one day after injection and 10.3 nmol/g seven days after injection. UDCA was undetectable in control retinas. Total serum UDCA was 0.86 umol/L one day after injection and 0.065 umol/L after seven days. For rats injected i.p. with vehicle, steady-state retina UDCA was 0.06 nmol/g and serum UDCA was 0.50 umol/L. For rats injected i.p. with TUDCA, steady-state retina UDCA was 7.1 nmol/g and serum UDCA was 6.2 umol/L.

Conclusions: : The results indicate that a single subconjunctival injection of TUDCA in fibrin sealant results in minimal serum levels of the compound while providing retina tissue levels of the drug well above those provided by a systemic injection dosage regimen that is protective in models of retinal degeneration.

Keywords: neuroprotection • drug toxicity/drug effects • retinal degenerations: cell biology