Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticinCitation formats

  • External authors:
  • Eva M. Del Amo
  • John R Griffiths
  • Izabela P Klaska
  • Justin Hoke
  • Anne White
  • James W.b. Bainbridge

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Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin. / Del Amo, Eva M.; Griffiths, John R; Klaska, Izabela P; Hoke, Justin; White, Anne; Aarons, Leon; Cooper, Garth J.s.; Bainbridge, James W.b.; Bishop, Paul N; Unwin, Richard D.

In: Molecular Pharmaceutics, 21.05.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Del Amo, E. M., Griffiths, J. R., Klaska, I. P., Hoke, J., White, A., Aarons, L., Cooper, G. J. S., Bainbridge, J. W. B., Bishop, P. N., & Unwin, R. D. (2020). Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.0c00151

Vancouver

Del Amo EM, Griffiths JR, Klaska IP, Hoke J, White A, Aarons L et al. Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin. Molecular Pharmaceutics. 2020 May 21. https://doi.org/10.1021/acs.molpharmaceut.0c00151

Author

Del Amo, Eva M. ; Griffiths, John R ; Klaska, Izabela P ; Hoke, Justin ; White, Anne ; Aarons, Leon ; Cooper, Garth J.s. ; Bainbridge, James W.b. ; Bishop, Paul N ; Unwin, Richard D. / Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin. In: Molecular Pharmaceutics. 2020.

Bibtex

@article{c1270ed7cbb3432db8bd91338369ecca,
title = "Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin",
abstract = "Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supra-normal concentrations supress preretinal neovascularisation. 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 h, 24 h, 72 h, 7 days, 14 days and 28 days post-injection (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 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 anti-angiogenic therapeutics. Whilst 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 non-pigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate and the turnover in vitreous is approximately 15% per day.",
keywords = "opticin, intravitreal pharmacokinetics, Selected reaction monitoring mass spectrometry, SLRP, neovascularisation",
author = "{Del Amo}, {Eva M.} and Griffiths, {John R} and Klaska, {Izabela P} and Justin Hoke and Anne White and Leon Aarons and Cooper, {Garth J.s.} and Bainbridge, {James W.b.} and Bishop, {Paul N} and Unwin, {Richard D.}",
year = "2020",
month = may,
day = "21",
doi = "10.1021/acs.molpharmaceut.0c00151",
language = "English",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Intravitreal pharmacokinetic study of the anti-angiogenic glycoprotein opticin

AU - Del Amo, Eva M.

AU - Griffiths, John R

AU - Klaska, Izabela P

AU - Hoke, Justin

AU - White, Anne

AU - Aarons, Leon

AU - Cooper, Garth J.s.

AU - Bainbridge, James W.b.

AU - Bishop, Paul N

AU - Unwin, Richard D.

PY - 2020/5/21

Y1 - 2020/5/21

N2 - Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supra-normal concentrations supress preretinal neovascularisation. 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 h, 24 h, 72 h, 7 days, 14 days and 28 days post-injection (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 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 anti-angiogenic therapeutics. Whilst 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 non-pigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate and the turnover in vitreous is approximately 15% per day.

AB - Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supra-normal concentrations supress preretinal neovascularisation. 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 h, 24 h, 72 h, 7 days, 14 days and 28 days post-injection (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 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 anti-angiogenic therapeutics. Whilst 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 non-pigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate and the turnover in vitreous is approximately 15% per day.

KW - opticin

KW - intravitreal pharmacokinetics

KW - Selected reaction monitoring mass spectrometry

KW - SLRP

KW - neovascularisation

U2 - 10.1021/acs.molpharmaceut.0c00151

DO - 10.1021/acs.molpharmaceut.0c00151

M3 - Article

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

ER -