ArticleInvestigative ophthalmology & visual science2025
Presynaptic Changes in Mouse Rod Photoreceptors During Early Retinitis Pigmentosa.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Homeostatic plasticity is crucial for maintaining stable neural activity by adjusting strength and intrinsic properties of synapses. This mechanism is vital for normal nervous system function and plays a role in various neurological conditions, including retinal degenerations. Sensitive night vision has been shown in P23H/Gnat2-/- retinitis pigmentosa (RP) mice, which lack cone phototransduction and rely solely on rods, even after losing more than half of their rod photoreceptors. While homeostatic plasticity has been proposed as a potential explanation, the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the molecular basis of this phenomenon. Methods: Single cell RNA-sequencing (scRNA-seq) and bulk retina proteomics were used to investigate the transcriptomic and proteomic changes of the degenerating retinas in 1-month-old P23H/Gnat2-/- RP and Gnat2-/- control mice. Immunohistochemistry was used to analyze the expression of synaptic SNARE complex and vesicle proteins, SNAP25 and SYT1, in the outer plexiform layer, the site of rod axon terminals. Results: This study shows a significant upregulation of genes encoding synaptic SNARE complex and vesicle proteins (Snap25, Stxbp1, and Syt1) in P23H mouse rods. Bulk retina proteomics analysis shows trends toward upregulation of the corresponding proteins as well as upregulation of many matrix-associated and trans-synaptic-complex proteins. Immunohistochemistry shows persistent SYT1 and SNAP25 expression in the outer plexiform layer of P23H/Gnat2-/- mice despite significant rod death. Conclusions: Rod degeneration induces molecular changes in the P23H/Gnat2-/- mouse rods that suggest synaptic plasticity and strengthening of rod-rod bipolar cell synaptic transmission in early RP.
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