Combination Antioxidant/NSAID Therapies and Oral/Topical Ocular Delivery Modes for Prevention of Oxygen-Induced Retinopathy in a Rat Model.

Abstract:

:Given the complexity of oxygen-induced retinopathy (OIR), we tested the hypothesis that combination therapies and modes of administration would synergistically optimize efficacy for prevention of OIR. Newborn rats were exposed to neonatal intermittent hypoxia (IH) from the first day of life (P0) until P14 during which they received: (1) oral glutathione nanoparticles (nGSH) with topical ocular phosphate buffered saline (PBS); (2) nGSH with topical ocular Acuvail (ACV); (3) oral coenzyme Q10 (CoQ10) + ACV; (4) oral omega 3 polyunsaturated fatty acids (n-3 PUFAs) + ACV; (5) CoQ10 + n-3 PUFAs + PBS; or (6) CoQ10 + n-3 PUFAs + ACV. Treated groups raised in room air (RA) served as controls. At P14, pups were placed in RA with no treatment until P21. Retinal vascular pathology, ocular angiogenesis biomarkers, histopathology, and morphometry were determined. All combination treatments in IH resulted in the most beneficial retinal outcomes consistent with suppression of angiogenesis growth factors during reoxygenation/reperfusion and no significant adverse effects on somatic growth. nGSH + PBS also reversed IH-induced retinopathy, but had negative effects on growth. Simultaneously targeting oxidants, inflammation, and poor growth mitigates the damaging effects of neonatal IH on the developing retina. Therapeutic synergy with combination delivery methods enhance individual attributes and simultaneously target multiple pathways involved in complex diseases such as OIR.

journal_name

Nutrients

journal_title

Nutrients

authors

Beharry KD,Cai CL,Siddiqui F,D'Agrosa C,Zangaladze A,Mustafa G,Qadri A,Duggan TJ,Aranda JV

doi

10.3390/nu12071980

subject

Has Abstract

pub_date

2020-07-03 00:00:00

issue

7

issn

2072-6643

pii

nu12071980

journal_volume

12

pub_type

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