Abstract
Purpose :
Retinitis pigmentosa is a hereditary retinopathy that courses with photoreceptor cell death. The rd10 mouse model is suitable for the study of the cellular and molecular alterations that occur during neurodegeneration. Fatty acids and, especially, the n-3 polyunsaturated docosahexaenoic acid (DHA), are abundant in photoreceptor cells and they impact in the phototransduction cascade. Thus, lipidomics analysis can contribute to the knowledge of the molecular pathways that are altered in retinitis pigmentosa.
Methods :
C57BL/6J and rd10 mice were kept at a photoperiod of 12:12 (L:D) with a light intensity of 50 lux. At P25, animals were perfused to avoid contamination by blood fatty acids. Retinal fatty acids were assessed by lipid extraction with Folch method and resolution with GC/MS. Cryostat sections of the retina were obtained for morphological studies using immunohistochemistry.
Results :
Photoreceptor cell rows were decreased in the retina of rd10 compared to C57BL/6J mice. Recoverin and cone arrestin immunolabeling revealed alterations in the morphology of rods and cones. Moreover, outer segments were shortened, and rhodopsin was mislocated to the cell body. The total amount of fatty acids decreased by 29.4 % in the retina of rd10 mice. Some specific short-chain as well as long-chain saturated fatty acids dropped significantly in the rd10 retina. We also found a dropped in the monounsaturated vaccenic acid and hypogeic acid. Polyunsaturated fatty acids dropped in the retina of the dystrophic mouse too. Concretely, we observed a significant decrease in the n-6 linoleic and arachidonic acid and in the n-3 DHA. But the fall of DHA was more pronounced than the decrease of n-6, and the balance between n-6 and n-3 was altered in the rd10 retina. Furthermore, we found a positive correlation between specific long-chain saturated fatty acids, hypogeic acid and DHA and the number of photoreceptor rows.
Conclusions :
DHA fatty acid experiences the most pronounced decrease among fatty acids in the retina of retinitis pigmentosa mice model. The positive correlation between the number of photoreceptor cells and the content of fatty acid could be indicating the relevance of these fatty acids in cell survival. These results can apport new molecular targets and further therapeutic strategies. FEDER-PID2019-106230RB-I00. FPU16/04114, FPU18/02964. RETICS-FEDER RD16/0008/0016. IDIFEDER/2017/064, ACIF/2020/203.
This is a 2021 ARVO Annual Meeting abstract.