Opticin is an endogenous vitreous
glycoprotein that may have therapeutic
potential as it has been shown that supranormal concentrations suppress
preretinal neovascularization. Herein we investigated the pharmacokinetics
of opticin following intravitreal injection in rabbits. To measure
simultaneously concentrations of human and rabbit opticin, a selected
reaction monitoring mass spectrometry assay was developed. The mean
concentration of endogenous rabbit opticin in 7 uninjected eyes was
measured and found to be 19.2 nM or 0.62 μg/mL. When the vitreous
was separated by centrifugation into a supernatant and collagen-containing
pellet, 94% of the rabbit opticin was in the supernatant. Intravitreal
injection of human opticin (40 μg) into both eyes of rabbits
was followed by enucleation at 5, 24, and 72 h and 7, 14, and 28 days
postinjection (n = 6 at each time point) and measurement
of vitreous human and rabbit opticin concentrations in the supernatant
and collagen-containing pellet following centrifugation. The volume
of distribution of human opticin was calculated to be 3.31 mL, and
the vitreous half-life was 4.2 days. Assuming that rabbit and human
opticin are cleared from rabbit vitreous at the same rate, opticin
is secreted into the vitreous at a rate of 0.14 μg/day. We conclude
that intravitreally injected opticin has a vitreous half-life that
is similar to currently available antiangiogenic therapeutics. While
opticin was first identified bound to vitreous collagen fibrils, here
we demonstrate that >90% of endogenous opticin is not bound to
collagen.
Endogenous opticin is secreted by the nonpigmented ciliary epithelium
into the rabbit vitreous at a remarkably high rate, and the turnover
in vitreous is approximately 15% per day.