Early Müller Glial Activation and Retinal Ganglion Cell Synaptic Dysfunction in APP/PS1 Mice

Area of Science:

• Neuroscience
• Ophthalmology
• Cell Biology

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder with sensory dysfunctions.
• The retina offers insights into early neurodegenerative processes.
• Cellular mechanisms of AD-associated retinal pathology are not fully understood.

Purpose of the Study:

• To examine structural, functional, and glial alterations in the retina of the APP/PS1 mouse model across disease stages.
• To understand the role of Müller glia in early AD retinal pathology.
• To investigate retinal changes independent of amyloid plaque deposition.

Main Methods:

• Utilized the APP/PS1 mouse model.
• Conducted systematic examination of retinal structure, function, and glial cells.
• Performed electrophysiology, synaptic input analysis, and transcriptomic profiling.

Main Results:

• Early retinal thinning, impaired electrophysiology, and reduced synaptic input to RGCs were observed in young APP/PS1 mice.
• Pronounced Müller glial activation, including gliosis and morphological remodeling, occurred independently of retinal Aβ deposits.
• Dysregulation of genes involved in metabolism and oxidative stress was identified in AD retinas.

Conclusions:

• Müller glial remodeling is an early feature of AD retinal pathology.
• Retinal changes coincide with synaptic vulnerability of RGCs, preceding neuronal loss.
• Retinal glia may serve as early indicators and modulators of neurodegeneration in Alzheimer's disease.