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Srini Goverdhan, Maureen Gatherer, Andrew Lotery; A New Laser Induced Senescent Mouse Model of Geographic Dry Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1237.
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Blindness from dry Age-related macular degeneration (AMD) remains unaddressed. Animal models are crucial to study AMD mechanisms and evaluate novel treatment strategies. Dry geographic AMD (GA) primarily results from loss of the retinal pigment epithelium (RPE). Current models of dry AMD have limitations. These include transgenic ELOVL4 gene (TGE_mut+/−) mice which have no visible GA type lesions but develop RPE vacuolisation with sub-retinal debris. Sodium iodate has been used to target RPE, but this method causes secondary degeneration of photoreceptors and choriocapillaris. The 810 nm diode laser has near infrared wavelength with deeper retinal penetration. It has low xanthophyll absorption, minimising nerve fibre layer and retinal damage, and is mainly absorbed in the RPE/choroid. We aimed to recreate the age related loss of RPE seen in human dry AMD (GA) in a senescent mouse model using a 810nm wavelength diode retinal laser.
C57 wild type mice (ex-breeders aged 11-13 months) were used. In phase 1, low powered diode laser thermal burns ranging from invisible to visible were titrated in 14 mice. In the 2nd phase, confluent diode laser spots were applied in 1 quadrant of the retina (1.3mw power, 60 sec each) in 21 eyes. Eyes were photographed with FFA (Micron 3 imaging) at weeks 4, 8 and 12 to document visible RPE atrophy. RPE65, FITC-labeled peanut agglutinin, anti-Rhodopsin staining and ERG were used to document the time course of RPE cell death and photoreceptor integrity.
The appropriate post-laser duration needed for RPE atrophy to develop following laser applications was studied. This was crucial as mimicking age-related RPE atrophy that normally occurs over many years is difficult in an acute laser animal model. Initial phase 1 results showed solitary retinal lesions progressing towards atrophic type dry AMD by week 8. In phase 2, both phenotype and histology resembling human GA dry AMD (focal RPE atrophy with early photoreceptor degeneration) was confirmed in all mice at 8 weeks.
Using long wavelength diode laser, we have created a novel, robust and reproducible mouse model of dry geographic AMD. New models of dry AMD are crucial for developing and testing therapeutic interventions of autologous or stem cell derived RPE cell transplantation for dry AMD.
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