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Valeriy V Lyzogubov, Nalini S Bora, Puran S Bora; Polyethylene Glycol (PEG) Induced Mouse Model of Dry Age Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):1181.
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Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide. Understanding the mechanisms responsible for dry AMD during its initial phases will be highly beneficial in designing new therapeutic strategies for the treatment of dry AMD. The aim of this study was to characterize dry AMD-like changes in mouse RPE and retina after PEG treatment.
We injected male C57BL/6 mice subretinally with PBS, 0.025, 0.25, 0.5 and 1.0 mg of PEG-400 and the animals were sacrificed on day 5. Eyes were harvested and processed for histological analysis. In all other experiments 0.5 mg PEG was injected and animals were sacrificed on days 1, 3, 5 or 14. Paraffin sections were used for TUNEL staining. Immunofluorescent staining using paraffin sections were utilized to detect active Caspase 3 (Casp3act), Atg12 and proliferating cell nuclear antigen. Plastic sections were analyzed using light and electron microscopy. Measurement and quantification of morphometric parameters were performed using ImageJ program. Gene expression was studied in PEG injected eyes and PBS controls using RNA microarray.
Subretinal injection of 0.5 mg PEG caused a 32% reduction of outer nuclear layer (ONL) thickness, 61% decrease of photoreceptor outer and inner segment length, 49% decrease of nuclear density in the ONL and 31% increase of RPE cell density by day 5 post-injection. Maximum TUNEL positive nuclei in the ONL were detected at day 5 after PEG injection. Histological signs of apoptosis were observed in the ONL by light and electron microscopy. Degeneration, autophagy and proliferation of RPE cells was noted in PEG injected eyes. RNA microarray demonstrated that several genes including Mmp9, Htra1, Casp1, Lgals3, C3, Serping1, Cfi, Lpl, Cp, fgf2 were up-regulated in PEG injected eyes compared to PBS controls.
Intraocular administration of PEG leads to morphological changes in RPE and retina consistent with dry AMD. Furthermore, PEG treatment up-regulated several genes reported to be involved in human AMD. Collectively, these results suggest that this simple and fast model will be useful to investigate dry AMD pathogenesis and treatment.
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