Altered retinal dopamine homeostasis in murine models of retinitis pigmentosa

RP retinas additionally demonstrated higher levels of DA precursor l-3,4-dihydroxyphenylalanine (L-DOPA), as well as upregulated tyrosine hydroxylase gene expression, which suggest elevated DA synthesis. In parallel, we observed increased activity and expression of the catecholamine-metabolising enzyme catechol-O-methyltransferase (COMT) during retinal degeneration. Comparative tissue analysis with cortex, striatum, retina, and eye cup samples further highlighted COMT as a major contributor to catecholamine inactivation in the mouse retina.

Finally, RNA sequencing of P23H retinal extracts revealed widespread alterations related to the catecholaminergic system during disease progression, including upregulation of the solute carrier family 6 member 2 gene, encoding norepinephrine transporter, and the protein phosphatase 1 regulatory subunit 1B gene, which encodes DA- and cAMP-regulated neuronal phosphoprotein. In conclusion, these data demonstrate elevated DA levels in P23H and rd10 mouse retinas, along with several other biochemical changes in the catecholamine system, suggesting a hyperexcited state in early RP progression.