Establishing in vitro mES-RPE cells bearing S28C TIMP3 mutation toidentify mouse models for Age Related Macular Degeneration.


English Laserna

Document Type


Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory


Age-related macular degeneration (AMD) is a complex retinal disease and the current leading cause of progressive blindness in aging populations. AMD is caused by the degradation of the macula, the portion of the retina responsible for central high-resolution vision. Mutations in TIMP3 have been described to cause AMD in humans. The objective of this study is to characterize the molecular and cellular effects of a S28C TIMP3 mutation in retinal pigment epithelial cells (ES-RPE) differentiated from eight different mouse strains of various genetic backgrounds (CAST/EiJ,129S1/SvImJ, C57BL/6J, WSB/EiJ, NZO/HlLtJ, A/J, PWK/PhJ, and NOD/LtJ). In this report, three cell lines (129S1/SvImJ, CAST/EiJ, & C57BL/6J) are under investigation.To compare the effects between cell lines, as well as to the human iPS-RPE cells, methods included qRT-PCR and immunocytochemical staining to quantitatively analyze protein expression and localization. All three cell lines have shown decreased stem cell protein expression and increased RPE protein expression through the RPE maturation process. No murine strain has been excluded; however, to establish an AMD mouse model that accurately represents human AMD pathology for future research efforts, the continued analysis of the remaining five cell lines as well as subculture analysis post-RPE maturation will need to occur.

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