Apoptosis of Retinal Photoreceptors During Development In Vitro: Protective Effect of Docosahexaenoic Acid

Abstract

Abstract:When rat retinal cells are cultured in a serumfree medium, the photoreceptor cells start dying after 7 days. The addition of docosahexaenoic acid (DHA) to the cultures prevents the selective death of photoreceptors. Here it is shown that, unlike other retinal neurons, photoreceptors die through an apoptotic pathway. Hallmarks of apoptosis, such as nuclear fragmentation and condensation and DNA cleavage forming a ladder pattern on an agarose gel, were observed. The timing and high selectivity of the triggering of photoreceptor cell apoptosis suggest the existence of a programmed cell death. Compared with other fatty acids, DHA not only was the most effective in promoting photoreceptor survival, but also the only one to decrease the number of apoptotic nuclei. The results suggest that DHA is important among the factors preventing apoptosis of photoreceptors in the developing retina. A limitation in the availability of this fatty acid might trigger apoptosis as a result of the failure to develop functional photoreceptor outer segments.

Mechanisms of action of docosahexaenoic acid in the nervous system

“…Considering the fact that PS is the major negatively charged phospholipid class in many mammalian cell membranes and many of the signaling proteins such as protein kinases are influenced by PS (119-121), this alteration of PS content may have significant implications for cellular function. In contrast to the well-documented apoptotic effect of DHA (122)(123)(124)(125)(126)(127), only a few studies have indicated an antiapoptotic function for this fatty acid (128)(129)(130)(131). In each case, an antiapoptotic effect was observed only after preincubation with DHA before the induction of apoptosis.…”

Alteration of polyunsaturated fatty acid status and metabolism in health and disease

“…DHA is especially important in the development of the brain, the retina and the spermatozoids [9]. Other actions of DHA include the formation of free radicals in response to oxidative stress [10], transcriptional activation of genes [11] and the prevention of apoptosis [12]. Impaired PUFA status is observed in numerous physiological state and chronic diseases.…”

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

“…For example, PEDF significantly enhances the release of neuroprotectin D1, a neuroprotectant derivative of DHA with antiangiogenic, antioxidant, and anti-inflammatory properties in the retina and CNS (61)(62)(63). Moreover, PEDF, DHA, and neuroprotectin D1 exert neurotrophic activity by delaying the onset of the apoptotic pathway, including increases in antiapoptotic Bcl-2 protein levels (40,62,64,65). Thus, a plausible upstream mechanism for transmitting PEDF signal in retina cells might involve DHA release by PEDF-R at the cell surface.…”