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A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
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prominin-1-null Xenopus laevis develop subretinal drusenoid-like deposits, cone-rod dystrophy and RPE atrophy
Brittany J Carr1,2, Dominic Skitsko3, Linnea M Kriese1,2
1The University of Alberta, Faculty of Medicine and Dentistry, Department of Ophthalmology and Visual Sciences, Edmonton, AB T6G 2E1, Canada.
Journal of Cell Science
|October 2, 2024
Summary
Genetic variants in Prominin-1 (PROM1) cause inherited vision loss. A frog model shows PROM1 deficiency leads to retinal pigment epithelium dysfunction and drusen-like deposits before photoreceptor degeneration.
Area of Science:
- Ophthalmology
- Genetics
- Developmental Biology
Background:
- Prominin-1 (PROM1) gene variants are linked to inherited, non-syndromic vision impairment.
- The precise mechanism of PROM1-associated retinal degeneration remains incompletely understood.
Purpose of the Study:
- To investigate the role of Prominin-1 in retinal health and disease progression using a Xenopus laevis model.
- To elucidate the cellular and molecular events underlying PROM1-deficiency-mediated retinal degeneration.
Main Methods:
- CRISPR/Cas9 gene editing was employed to create prom1-null mutations in Xenopus laevis.
- Retinal disease progression was monitored longitudinally from 6 weeks to 3 years of age.
- Histology, optical coherence tomography (OCT), and color fundus photography were used to assess retinal structure and pathology.
Main Results:
- Prom1-null frogs exhibited age-dependent retinal degeneration.
- Retinal pigment epithelium (RPE) dysfunction, including thinning and disorganization, preceded photoreceptor degeneration.
- Subretinal drusenoid deposit (SDD)-like structures accumulated in the subretinal space and outer segment layer.
- Evidence suggested an RPE origin for the SDD-like deposits, including pigment granule infiltration.
Conclusions:
- Prom1-null-associated blindness involves RPE dysfunction and death preceding photoreceptor degeneration.
- The findings challenge the previous hypothesis of direct effects on photoreceptor outer segment morphogenesis.
- This Xenopus model provides insights into the pathogenesis of PROM1-related inherited retinal diseases.
