Decreased docosahexaenoic acid and other specific fatty acids in a mouse model of retinal degeneration

Abstract

PurposeRetinal degeneration compromises retinal metabolism and signaling, including lipid pathways. Fatty acids are highly enriched in the retina and they impact photoreceptor survival. In this study, we aimed to identify fatty acids that could be relevant in retinal degeneration. For this purpose, we analyzed the fatty acid profile of the retina of rd10 mice, model of retinitis pigmentosa.MethodsFatty acids of the retina of C57BL/6J and rd10 mice were extracted by the Folch method and analyzed by GC/MS. Morphological changes were studied by immunohistochemistry.ResultsIn the retina of rd10 mice, there was a drop of photoreceptor rows compared to healthy retinas. Rhodopsin, a protein expressed in outer segments, was delocalized into the cell bodies of photoreceptors in dystrophic retinas, and axons and outer segments of cones were shortened. In these animals, we found a decrease of specific saturated, monounsaturated and polyunsaturated fatty acids. Remarkably, docosahexaenoic acid (DHA) experienced a marked drop, leading to a heightening of the n‐3/n‐6 ratio, an indicator of inflammation. We found a positive correlation of cerotic acid, hypogeic acid, and DHA with photoreceptor rows.ConclusionsSpecific saturated and unsaturated fatty acids dropped in retinitis pigmentosa. Remarkably, diminished levels of the omega‐3 DHA could be contributing to the neurodegeneration process due to a shift to pro‐inflammatory pathways and a lack of neuroprotective signals, promoting photoreceptor death. Fatty acids could have decisive roles in the retinal degeneration outcome and should be considered to improve therapy.MICINN‐FEDER PID2019‐106230RB‐I00; RETICS‐FEDER RD16/0008/0016; ACIF/2020/203; IDIFEDER/2017/064; FPU16/04114; FPU18/02964.