Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Cell Biology

Background:

• Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss.
• Current treatments for AMD are limited, highlighting the need for novel therapeutic strategies.
• Cell replacement therapy, particularly using retinal pigment epithelium (RPE) cells, shows promise for AMD treatment.

Purpose of the Study:

• To establish and characterize a novel mouse model of AMD using systemic sodium iodate injection.
• To evaluate the efficacy of human embryonic stem cell (hESC)-derived RPE cell transplantation in this AMD model.
• To assess the potential of this model for studying RPE cell transplantation and disease progression.

Main Methods:

• Induction of RPE and photoreceptor damage in mice via systemic sodium iodate injection.
• Monitoring of morphological, functional, and behavioral changes using histology, gene expression, electroretinography, and optokinetic tracking.
• Transplantation of hESC-derived RPE cells one week post-injection, with analysis three weeks later.

Main Results:

• Sodium iodate injection led to complete RPE loss, photoreceptor degeneration, and functional vision impairment.
• Transplanted hESC-derived RPE cells formed organized monolayers with wild-type morphology and function.
• Donor RPE cells demonstrated phagocytic activity, integrating effectively into the host retina.

Conclusions:

• Systemic sodium iodate injection creates a robust model for studying AMD and evaluating RPE cell transplantation.
• The model facilitates the assessment of RPE cell reconstitution and maturation following transplantation.
• The RPE-free environment in this model supports the formation of extensive, polarized RPE monolayers from cell suspensions.