ApoER2 function in the establishment and maintenance of retinal synaptic connectivity

Area of Science:

• Neuroscience
• Ophthalmology
• Molecular Biology

Background:

• Inner retinal circuitry development mechanisms remain unclear.
• Reelin and apolipoprotein E (apoE) are implicated in retinal development and degeneration.
• Apolipoprotein E receptor 2 (ApoER2) function in the retina is not well-defined.

Purpose of the Study:

• To investigate the role of ApoER2 in the developing and adult retina.
• To elucidate the function of ApoER2 in retinal synaptic development and maintenance.

Main Methods:

• Analysis of ApoER2 expression patterns in retinal cells.
• Phenotypic characterization of ApoER2 knockout (KO) mice.
• Assessment of retinal function in KO mice models.

Main Results:

• ApoER2 expression peaks during postnatal retinal synaptic development, primarily in A-II amacrine cells.
• ApoER2 KO mice exhibit rod bipolar morphogenic defects, altered amacrine cell development, and impaired rod-driven responses.
• The NPxY motif of ApoER2, but not exon 19, is essential for rod bipolar pathway development.
• VLDLR deficiency affects amacrine cell development and retinal responses.
• Both ApoER2 and VLDLR KO mice show age-related declines in rod and cone function.

Conclusions:

• ApoER2 plays a critical role in establishing and maintaining normal retinal synaptic connectivity.
• ApoER2 and VLDLR are important for distinct aspects of retinal development and function.
• Age-related vision decline may be linked to the function of these Reelin receptors.