Resumo

Introduction: During the development of the mammalian visual system, synaptic refinement depends on spontaneous electric activity of retinal ganglion cells (RGCs), mostly through GABAergic and cholinergic inputs until postnatal day 12 (DPN 12). Essential fatty acids (EFAs), accumulated during fetal period and neonatal development, appear as precursors of signaling molecules including retrograde messengers and transcription factors. Docosahexaenoic acid (DHA), the final bioactive lipid of the omega-3 fatty acids family chain, is the main polyunsaturated fatty acid in the brain and retina and exerts their effects on brain function through various mechanisms, including some involved in the modulation of glutamate receptors and trophic factors. Here, we tested the effect of omega-3 fatty acids in the development of retinal morphology, particularly, the differentiation of photoreceptors and the cholinergic and GABAergic markers involved in spontaneous activity during the critical period. Methods: Female Lister Hooded rats were fed during 5 weeks before mating with either control (soy oil) or restricted (coconut oil) diets. After birth, litters were fed (30g/day/animal) until postnatal day (PND) 7, 14 and 21. Sections were labeled with antibodies to photoreceptors, cholinergic and GABAergic markers (anti-rhodopsin, anti-vChat and anti-GABA, respectively). Retinae were also stained with either cresyl violet or neutral red. Results: The morphological analysis of retinal tissue revealed a significant reduction in the thickness in the outer nuclear ( 17,02%) and inner plexiform layers (17,24 %) as compared to control sections at PND14 and EFAs restriction resulted in the reduction of rhodopsin expression at PND 7 and PND 14. Also, restricted EFAs restriction resulted in decreased immunoreactivity for the acetylcholine transporter (vChat) from PND7-21 at the inner plexiform layer. In the experimental group, GABA immunoreactivity in the inner nuclear and plexiform layers was significantly reduced at PND 7 and increased at PND14 when compared to the control group. Moreover, via the technique of neutral red observed that even at P14 we observed pyknotic nuclei present in retinal tissue, indicating that it is occurring developmental delay. Conclusions: Altogether, the data indicate that food restriction of DHA promotes morfofunctional changes in the retina with delayed differentiation of the photoreceptor population and also in the population of cholinergic and GABAergic amacrine cells. These results are, therefore, consistent with a role for EFAs in the development of neurochemical differentiation of the retina with impact in the development of retinal circuits.