Presynaptic Changes in Mouse Rod Photoreceptors During Early Retinitis Pigmentosa

Area of Science:

• Neuroscience
• Ophthalmology
• Molecular Biology

Background:

• Homeostatic plasticity is essential for neural stability, adjusting synaptic strength and intrinsic properties.
• This mechanism is vital for nervous system function and implicated in neurological disorders like retinal degenerations.
• P23H/Gnat2-/- retinitis pigmentosa (RP) mice exhibit sensitive night vision despite significant rod loss, suggesting underlying homeostatic plasticity.

Purpose of the Study:

• To investigate the molecular mechanisms behind homeostatic plasticity in degenerating retinas of P23H/Gnat2-/- RP mice.
• To understand how rods adapt to degeneration and maintain synaptic function.

Main Methods:

• Single cell RNA-sequencing (scRNA-seq) and bulk retina proteomics were employed to analyze transcriptomic and proteomic changes.
• Immunohistochemistry was used to examine the expression of synaptic proteins SNAP25 and SYT1 in the outer plexiform layer.

Main Results:

• Significant upregulation of genes encoding synaptic SNARE complex and vesicle proteins (Snap25, Stxbp1, Syt1) was observed in P23H mouse rods.
• Proteomics revealed trends toward upregulation of corresponding proteins and other synaptic-associated proteins.
• Persistent expression of SYT1 and SNAP25 was confirmed in the outer plexiform layer despite substantial rod photoreceptor death.

Conclusions:

• Rod degeneration in P23H/Gnat2-/- mice induces molecular changes indicative of synaptic plasticity.
• These changes suggest a strengthening of rod-rod bipolar cell synaptic transmission as an early adaptive response in retinitis pigmentosa.