6533b81ffe1ef96bd1276e09

RESEARCH PRODUCT

Participation des facteurs nutritionnels et environnementaux au vieillissement de la rétine et aux rétinopathies liées à l’âge

subject

description

Aging is defined by all the physiological processes that alter the structure and functions of the body. With advanced age, aging of the human retina can evolve into pathological forms, agerelated macular degeneration (AMD) or diabetic retinopathy (DR). The mechanisms involved in the transition from normal aging to a pathologic state are poorly understood. Oxidative stress and advanced glycation end-products are promoting factors for aging of the retina. Meanwhile, epidemiological studies suggest that a diet rich in long-chain omega-3 polyunsaturated fatty acids (LC-PUFA) such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), potentially protects against the development of AMD and insulin resistance, the main risk factor for DR. However, the mechanisms surrounding the effects of omega-3 LC-PUFA on aging of the retina are largely undefined. Interestingly, the protective effects of omega-3 LC-PUFA were greater when the intake in omega 6 linoleic acid was low. A better understanding of the mechanisms and consequences of aging on the retina on the one hand, and of the effects of omega-3 LC-PUFA on aging of the retina on the other hand, is warranted. Within this context, our research objectives were to assess: 1 - the impact of endogen and environmental factors, known to trigger oxidative stress, advanced glycation end-products (AGEs) or insulin resistance, on the function and aging of the retina, and 2 - the response of the retina to a omega-3 LC-PUFA-enriched diet. The effects of nutritional, environmental or endogenous factors generating oxidative stress and AGEs on the retina were tested in a murine model of aging of the human retina: the ApoB100,LDLR-/- mouse. Our results showed an alteration of the retinal function assessed by electroretinography, associated with the accumulation of microglial cells and/or macrophages in the outer retina in animals exposed to oxidative stress and AGEs. Insulin resistance triggered by a fructoseenriched diet had similar effects on retinal function: reduced response of the photoreceptors and loss of rod sensitivity. In addition, the expression of genes coding proteins involved in lipid metabolism, and nuclear factors such as PPARd and LXRα was modulated. Following the nutritional guidelines that would prevent the development of AMD improved the incorporation of omega-3 LC-PUFA in the retina and modulated the expression of the LDLreceptor gene in the neurosensory retina without changes in retinal function. 8 In conclusion, our works reported the adaptative response of the retina to environmental and endogenous factors known to promote aging of the retina. It included the impairment of the retinal function, and the modulation of gene expression. Our data also gave a better understanding of the effects of omega-3 LC-PUFA against aging of the retina. Lastly, our data support and suggest new roles of lipids and lipid metabolism in aging of the retina, and in the development of age-related disorders.