Localization of Ceramide Synthase 5 in Mouse Retina

Ceramide synthases (CerS) are key enzymes in sphingolipid metabolism that regulate fundamental cellular processes, including apoptosis, cell growth, and homeostasis. Among the six known mammalian isoforms (CerS1-CerS6), CerS5 has been particularly well studied for its involvement in the synthesis of the sphingolipid C16-ceramide. However, its expression, localization, and functional significance of CerS5 in the retina remain unclear. In the present study, we investigated the presence, distribution, and functional role of CerS5 in mouse retina using CerS5 knockout (KO) mice. We performed quantitative polymerase chain reaction, X-gal staining, and immunohistochemistry to analyze the expression and localization. Electroretinography (ERG) was employed to assess the impact of CerS5 deficiency on retinal function. Our results demonstrated that CerS5 is localized to the inner nuclear layer and ganglion cell layer, co-localizing with horizontal cells and specific subsets of amacrine and ganglion cells. The retina of CerS5 KO mice showed a reduction in overall thickness, with significant thinning observed in all retinal layers except the photoreceptor, whereas the outer plexiform layer showed increased thickness. Despite these structural alterations, ERG recordings revealed no significant changes in retinal function. These findings suggest that CerS5 contributes to the maintenance of retinal structural integrity, particularly through its presence in specific retinal cell types, whereas its loss does not markedly impair retinal function in adult mice. The observed structural alterations highlight its potential role in retinal physiology and possible implications for retinal pathophysiology, warranting further investigation into compensatory mechanisms by other ceramide synthase isoforms.