Nutrition for the eye: different susceptibility of the retina and the lacrimal gland to dietary omega-6 and omega-3 polyunsaturated fatty acid incorporation.

The purpose of this study was to compare the susceptibility of the retina and the exorbital lacrimal gland to dietary supplies of long-chain omega-3 (omega3) and omega-6 (omega6) polyunsaturated fatty acids (LC-PUFAs). Male Wistar rats were fed a 5% lipid diet containing: (1) 10% eicosapentaenoic acid (EPA) and 7% docosahexaenoic acid (DHA), or (2) 10% gamma-linolenic acid (GLA), or (3) 10% EPA, 7% DHA and 10% GLA or (4) a balanced diet deprived of EPA, DHA and GLA for 3 months. Lipids were extracted from plasma phospholipids, retina and exorbital lacrimal gland, and fatty acid composition was determined by gas chromatography. Dietary supplementation with EPA and DHA increased omega3 PUFA levels in plasma phospholipids as well as in the retina and the exorbital lacrimal gland. By contrast, GLA supplementation favored omega6 PUFA incorporation, and particularly the incorporation of the end-chain omega6 product, docosapentaenoic acid (DPA), into all tissues. Supplementation with EPA, DHA and GLA increased the levels of DHA, EPA and dihomo-GLA (dGLA), whereas arachidonic acid (AA) was unchanged and DPA decreased in the retina and the lacrimal gland. The ability of both tissues to incorporate PUFAs from blood was evaluated. The results showed that the retina was more selective than the lacrimal gland for EPA. In spite of the different susceptibility of the retina and the lacrimal gland to dietary PUFAs, these results suggest that the concomitant use of dietary omega3 and omega6 PUFAs may be useful in modulating inflammation in both tissues.

Lipid and fatty acid profile of the retina, retinal pigment epithelium/choroid, and the lacrimal gland, and associations with adipose tissue fatty acids in human subjects.

Accumulation of lipids within Bruch's membrane (BrM) and between BrM and retinal pigment epithelium (RPE) accounts for one of the biological changes associated with normal aging and may contribute to the development of age-related maculopathies. The origin of these lipids is still being actively investigated. The relative contribution of plasma lipids and lipids coming from the neural retina remains a matter of controversy. Low-density lipoproteins (LDLs) have been reported to significantly participate in the retina's lipid supply, after active remodeling within RPE. Meanwhile, RPE expresses the enzymatic machinery for synthesizing lipoprotein-like particles. The objective of this study was to establish associations between the fatty acid profile of the ocular structures and adipose tissue as a surrogate for the subjects' past dietary intake. Lipids and fatty acids were analyzed from the neural retina, retinal pigment epithelium (RPE)/choroid, the lacrimal gland, and adipose tissue, collected from 27 human donors (19 women, eight men) aged 59-95 years. DHA concentrations in the neural retina were positively associated with the concentrations in cholesteryl esters (CEs) from RPE/choroid and negatively associated with DHA concentrations in phospholipids (PLs) from RPE/choroid. DHA in orbital fat was positively associated with DHA in the lacrimal gland. No significant association was observed in the other ocular structures. Linoleic acid in orbital fat was positively associated with linoleic acid in the lacrimal gland, followed by the neural retina and CEs from RPE/choroid; it was slightly correlated with PLs from RPE/choroid. Other fatty acids that originate exclusively from the diet such as trans fatty acids were detected in orbital fat, the lacrimal gland, PLs, and CEs from RPE/choroid. DHA in the neural retina was poorly associated with its dietary intake, contrary to other fatty acids such as linoleic acid. Within this context, CEs may be important carriers of fatty acids entering the retina. Although epidemiological studies have reported the benefit of DHA in the prevention of age-related macular degeneration, the leading cause of blindness in Western countries, the relevance of supplementing patients with DHA is questioned.

Modulation of secretory functions in epithelia by adenovirus capsid proteins.

To evaluate the safety of adenovirus-derived capsid proteins for ocular gene delivery, we have investigated their effects on the morphology and function of the acinar epithelial cells of the lacrimal gland. These cells are responsible for basal and stimulated release of proteins and electrolytes into ocular fluid, a process essential in maintaining the health of the ocular surface. Acinar epithelial cells from rabbit lacrimal gland were exposed to one of two adenovirus serotype 5 capsid proteins, penton or knob (the carboxy-terminal fragment of the fiber capsid protein). Sustained (16-18 h) exposure to the penton at 20 microg/ml was associated with major changes in the organization of the regulated secretory pathway and cytoskeleton. These changes included an apparent loss of mature secretory vesicles enriched in rab3D around the apical lumen as well as a depletion of apical actin. The microtubule array in penton-treated acini also exhibited bundling and disorganization. None of these effects were elicited by exposure to knob protein. Penton treatment also caused a significant (p < or = 0.05) increase and decrease in basal and carbachol-stimulated release, respectively, of bulk protein. Competition studies showed that RGD peptide partially prevented the penton-induced changes in rab3D-enriched secretory vesicles and actin filaments. These findings suggest that the adenovirus penton protein compromises normal acinar secretory compartment organization and function and that these changes are due at least partly to penton-integrin interactions.