title: Polyethylene glycol induced mouse model of retinal degeneration.
abstract: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness. This study was done to characterize dry AMD-like changes in mouse retinal pigment epithelium (RPE) and retina after polyethylene glycol (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, 5 μm and plastic, 1 μm and 80 nm sections were used for further analysis. Subretinal injection of 0.5 mg PEG induced 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 after injection. The maximum level of TUNEL positive nuclei in the ONL (6.8 + 1.99%) was detected at day 5 after PEG injection and co-localized with Casp3act. Histological signs of apoptosis were observed in the ONL by light or electron microscopy. Degeneration of RPE cells was found in PEG injected eyes. Gene expression data identified several genes reported to be involved in human AMD. C3, Cfi, Serping1, Mmp9, Htra1 and Lpl were up-regulated in PEG injected eyes compared to PBS controls. PEG leads to morphological and gene expression changes in RPE and retina consistent with dry AMD. This model will be useful to investigate dry AMD pathogenesis and treatment.
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Valeriy V
authors.initials: VV
authors.lastname: Lyzogubov
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Ruslana G
authors.initials: RG
authors.lastname: Tytarenko
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: pbora@uams.edu.
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
mesh_terms: D000626:Aminopeptidases / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D050718:Complement C1 Inhibitor Protein / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology; D057092:Geographic Atrophy / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D020287:In Situ Nick-End Labeling; D056965:Injections, Intraocular; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D011092:Polyethylene Glycols / Q000633:toxicity*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D012697:Serine Endopeptidases / Q000235:genetics; D013997:Time Factors
chemical_list: D050718:Complement C1 Inhibitor Protein; D003176:Complement C3; C487284:Serping1 protein, mouse; C010073:chemotactic factor inactivator; D011092:Polyethylene Glycols; D000626:Aminopeptidases; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: age-related macular degeneration; mouse model; pathology; retinal degeneration