Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Wet and Dry Age-Related Macular Degeneration Induced by Polyethylene Glycol

Version 1 : Received: 17 July 2023 / Approved: 18 July 2023 / Online: 19 July 2023 (09:24:37 CEST)

How to cite: Mitchell, R.; Logan, C.; Lyzogubov, V.V.; Bora, N.S.; Bora, P.S. Wet and Dry Age-Related Macular Degeneration Induced by Polyethylene Glycol. Preprints 2023, 2023071318. https://doi.org/10.20944/preprints202307.1318.v1 Mitchell, R.; Logan, C.; Lyzogubov, V.V.; Bora, N.S.; Bora, P.S. Wet and Dry Age-Related Macular Degeneration Induced by Polyethylene Glycol. Preprints 2023, 2023071318. https://doi.org/10.20944/preprints202307.1318.v1

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

Keywords

Age-related macular degeneration, Choroidal neovascularization, Retinal pigmented epithelium, Fluorescein isothiocyanate

Subject

Medicine and Pharmacology, Ophthalmology

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