Abstract
Purpose :
Opticin is an endogenous, anti-angiogenic, extracellular glycoprotein found in the vitreous that binds to vitreous collagen fibrils. Opticin has potential therapeutic value as an anti-angiogenic agent in conditions such as proliferative diabetic retinopathy. The purpose of this study was to investigate the pharmacokinetic (PK) profile of intravitreally delivered opticin in rabbits.
Methods :
Eighteen New Zealand rabbits were intravitreally injected in both eyes with 40 µg of human opticin (50 µl). Eyes were enucleated at 5 h, 24 h, 72 h, 7 days, 14 days, 28 days (n=5-6). The vitreous was extracted and the free and collagen bound concentrations of human opticin were measured by mass spectrometry using selected reaction monitoring. The concentration of free and collagen-bound endogenous opticin in rabbit vitreous was also measured within the same method. The resulting PK data was analysed by Nonlinear Mixed Effects Method (Monolix software®) using a one compartmental model. The interplay between the exogenous and endogenous opticin in the vitreous was also investigated.
Results :
The injected human opticin presented a first-order elimination profile with an intravitreal volume of distribution of 3.18 ml, clearance of 0.022 ml/h and half-life of 4.1 days. The concentrations of free and collagen bound rabbit opticin in the uninjected eyes were 0.60 and 0.04 ng/ml respectively. With the human opticin injection, more than 20-fold increase over the rabbit opticin was reached with a possible partial replacement of the collagen-bound rabbit opticin by the human one. This effect is reversed as the human opticin is cleared from the eye.
Conclusions :
Opticin has a half-life in the eye comparable to that of aflibercept. Its long half-life is a consequence of its binding to collagen fibrils. Reversible displacement of the natural bound opticin was observed.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.