Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Mammalian Animal & Human Retinal Organ Culture as Pre-clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics

Martina Kropp
* ORCID logo ,
Mohit Mohit
,
Cristina Ioana Leroy-Ciocanea
,
Laura Schwerm
,
Nina Harmening
ORCID logo ,
Thais Bascuas
ORCID logo ,
Eline De Clerck
ORCID logo ,
Andreas J. Kreis
,
Bojan Pajic
,
Sandra Johnen
ORCID logo ,
Gabriele Thumann
*
Version 1 : Received: 10 May 2023 / Approved: 10 May 2023 / Online: 10 May 2023 (09:42:33 CEST)

A peer-reviewed article of this Preprint also exists.

Kropp, M.; Mohit, M.; Leroy-Ciocanea, C.I.; Schwerm, L.; Harmening, N.; Bascuas, T.; De Clerck, E.; Kreis, A.J.; Pajic, B.; Johnen, S.; Thumann, G. Mammalian Animal and Human Retinal Organ Culture as Pre-Clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics. Antioxidants 2023, 12, 1211. Kropp, M.; Mohit, M.; Leroy-Ciocanea, C.I.; Schwerm, L.; Harmening, N.; Bascuas, T.; De Clerck, E.; Kreis, A.J.; Pajic, B.; Johnen, S.; Thumann, G. Mammalian Animal and Human Retinal Organ Culture as Pre-Clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics. Antioxidants 2023, 12, 1211.

Abstract

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed models’ quality, induced OS, and tested efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by high-glucose or hydrogen peroxide (H2O2) and treated by Scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage-colony stimulating factor (GM-CSF). Tissue morphology, cell viability, inflammation, and glutathione level were determined. Retina samples showed only moderate necrosis (23.83±5.05 increased to 27.00±1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3±59.9 vs. 435.7±166.8 nM ATP in controls); antioxidants reduced OS-induced apoptosis (from 124.20±51.09 to 60.80±319.66 cells/image after scutellarin-treatment). Enhanced mammalian animal and human retina cultures allow reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Keywords

retina organ culture; neuroretinal degenerative disease; oxidative stress; antioxidant; age-related macular degeneration (AMD); diabetic retinopathy (DR); Scutellarin; PEDF; GM-CSF; 4R

Subject

Medicine and Pharmacology, Ophthalmology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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