Format

Send to

Choose Destination
Sci Rep. 2019 May 16;9(1):7475. doi: 10.1038/s41598-019-43906-z.

A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy.

Author information

1
Biological Sciences, University of Southampton, SGH, South Lab and Path Block, MP840, Tremona Road, Southampton, SO16 6YD, United Kingdom.
2
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton, SO16 6YD, United Kingdom.
3
Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom.
4
Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton, SO16 6YD, United Kingdom.
5
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton, SO16 6YD, United Kingdom. A.J.Lotery@soton.ac.uk.
6
Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, United Kingdom. A.J.Lotery@soton.ac.uk.
7
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton, SO16 6YD, United Kingdom. J.Ratnayaka@soton.ac.uk.

Abstract

Early stages of geographic atrophy (GA) age-related macular degeneration is characterised by the demise of photoreceptors, which precedes the loss of underlying retinal pigment epithelial (RPE) cells. Sight-loss due to GA has no effective treatment; reflecting both the complexity of the disease and the lack of suitable animal models for testing potential therapies. We report the development and characterisation of a laser-induced mouse model with early GA-like pathology. Retinas were lasered at adjacent sites using a 810 nm laser (1.9 J/spot), resulting in the development of confluent, hypopigmented central lesions with well-defined borders. Optical Coherence Tomography over 2-months showed progressive obliteration of photoreceptors with hyper-reflective outer plexiform and RPE/Bruch's membrane (BrM) layers within lesions, but an unaffected inner retina. Light/electron microscopy after 3-months revealed lesions without photoreceptors, leaving the outer plexiform layer apposed to the RPE. We observed outer segment debris, hypo/hyperpigmented RPE, abnormal apical-basal RPE surfaces and BrM thickening. Lesions had wedge-shaped margins, extended zones of damage, activated Müller cells, microglial recruitment and functional retinal deficits. mRNA studies showed complement and inflammasome activation, microglial/macrophage phagocytosis and oxidative stress providing mechanistic insights into GA. We propose this mouse model as an attractive tool for early GA studies and drug-discovery.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center