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other·ophthalmology, retina, preclinical research, biomedical research·PMC10178932

The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy

Journal of Ocular Pharmacology and Therapeutics · 5 authors, 3 centres

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TL;DR

This preclinical study evaluated the antiangiogenic effects of three modified NSAIDs in models of retinal neovascularization.

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This preclinical study evaluated the antiangiogenic effects of three modified NSAIDs in models of retinal neovascularization. Using the mouse oxygen-induced retinopathy (OIR) model, researchers measured changes in the avascular area (AVA) and neovascular area (NVA) of the retina. A single intravitreal injection of Q-922 or OXT-328 significantly reduced both AVA and NVA. CL-717 administered as topical eye drops over 5 days also reduced AVA and NVA, while topical OXT-328 had no effect. Systemic (intraperitoneal) administration of Q-922 also reduced AVA and NVA. In a chicken chorioallantoic membrane (CAM) assay, all three compounds reduced new blood vessel formation by approximately one-third. Human eye explants bathed in CL-717 showed rapid uptake and biodistribution. Mild ocular surface irritation was noted only with topical Q-922. The study concludes that systemic Q-922 and topical CL-717 show promise for treating proliferative retinopathies without intravitreal injections, though the mechanism is not fully understood and the human relevance is based on ex vivo tissue only.

STUDY TYPE

other

SPECIALTY

ophthalmology

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AI pipeline

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ORIGINAL PAPER

PMC10178932

The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy

Journal of Ocular Pharmacology and Therapeutics

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ABSTRACT

Abstract Purpose: To evaluate the hypothesis that 3 novel compounds, OXT-328, Q-922, and CL-717 show efficacy in the treatment of oxygen-induced retinopathy (OIR) and whether or not their route of administration is intravitreal, topical, or systemic. Methods: The OIR mouse model, characterized by an avascular area (AVA) and a neovascular area (NVA) of the retina, was used to study retinopathy of prematurity and other retinal diseases characterized by abnormal vessel growth. We measured the effect of our compounds on both the AVA and NVA in whole mounts of mouse retinal tissue. We also evaluated their ability to prevent new vessel formation in chicken chorioallantoic membranes (CAMs). Finally, we measured the in vitro uptake and biodistribution of topically applied CL-717 in human eye explants. Results: In mice with OIR, compared to controls, a single intravitreal administration of Q-922 or OXT-328 significantly reduced both AVA and NVA. CL-717 administered as eye drops over 5 days also reduced AVA and NVA, whereas OXT-328 eye drops had no effect. Q-922 given intraperitoneal (150 mg/kg/day × 5 days) reduced AVA and NVA. Remarkably, explanted human eyes bathed in CL-717 show rapid uptake and biodistribution in ocular tissues. In the chicken CAM model, all 3 compounds reduced the formation of new blood vessels by about one-third. No side effect in mice was observed, except for mild ocular surface irritation with Q-922. Conclusions: Systemic administration of Q-922 or topical administration of CL-717 holds particular promise for a simplified treatment of proliferative retinopathies without the necessity of intravitreal injections. Keywords: oxygen-induced retinopathy, OXT-328, Q-922, CL-717, abnormal vessel growth, retinal angiogenesis

CITATION EXPORT

Wei Huang, Liqun Huang, Ziyi Wen et al.. The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy. Journal of Ocular Pharmacology and Therapeutics. (2023). https://doi.org/10.1089/jop.2022.0113

AUTHORS

5 · 3 CENTRES

Wei Huang, Liqun Huang, Ziyi Wen, Robert A Honkanen, Basil Rigas

1Department of Ophthalmology, Population and Preventive Medicine, Stony Brook University, Stony Brook, New York, USA.
2Medicon Pharmaceuticals, Inc., Setauket, New York, USA.
3Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, New York, USA.