Researchers from the University of California, Irvine have discovered that the absence of Adiponectin receptor 1 protein (AdipoR1), one of the principal enzymes regulating ceramide homeostasis in the retina, leads to an accumulation of ceramides in the retina, resulting in progressive photoreceptor cell death and ultimately vision loss. The team also found that a combination of desipramine and L-cycloserine reduced lowered ceramide levels, which protected photoreceptors, helped preserve the retina’s structure and function, and improved vision.
Study findings show that ceramide imbalance damages the neural retina and retinal pigmented epithelium, accompanied by a significant reduction of electroretinogram amplitudes, decreased retinoid content in the retina, reduced cone opsin expression and massive inflammatory response. A buildup of ceramides in the retina, likely due to insufficient ceramidase activity, led to photoreceptor death. When treated with the desipramine and L-cycloserine combination, ceramide levels were lowered, which helped preserve photoreceptors in mice. The team also observed improved daylight vision in the L-cycloserine treated mice, and that prolonged treatment significantly improved electrical responses of the primary visual cortex to visual stimuli.