Inhibiting De Novo Biosynthesis of Ceramide by L-Cycloserine Can Prevent Light-Induced Retinal Degeneration in Albino BALB/c Mice

Retinal degenerative diseases lead to irreversible vision loss due to photoreceptor cell death, driven by complex genetic and environmental factors. Ceramide, a sphingolipid metabolite, emerges as a critical mediator in the apoptotic cascade associated with retinal degeneration. Our previous work demonstrated L-Cycloserine's ability to protect photoreceptor-derived cells from oxidative stress by inhibiting the de novo ceramide pathway and thus prompting further investigation on its effect in the in vivo retina. This study investigates the potential of L-Cycloserine to protect albino BALB/c mice against light-induced retinal degeneration (LIRD). L-Cycloserine, in an optimal dose, administered systemically 30 min before LIRD, was found to prevent photoreceptor cell death significantly from light-induced degeneration. We further determined the retinal bioavailability and pharmacokinetic behavior of L-Cycloserine, its effect on sphingolipid profile, expression of sphingolipid biosynthetic, and cell death-promoting genes and proteins from the retina to understand the underlying mechanisms. This study lays the groundwork for further preclinical and clinical investigations into L-Cycloserine's potential as a novel therapeutic in treating retinal degenerative diseases.