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The ERK/MAPK signaling pathway is involved in several cellular functions. Inactivation in mice of genes encoding members of this pathway is often associated with embryonic death resulting from abnormal placental development. The placenta is essential for nutritional and gaseous exchanges between maternal and embryonic circulations, as well as for the removal of metabolic wastes. These exchanges take place without direct contact between the two circulations. In mice, the hematoplacental barrier consists in a triple layer of trophoblast cells and endothelial cells of the embryo. MEK1 and MEK2 are double specificity serine-threonine/tyrosine kinases responsible for the activation of ERK1 and ERK2. Mek1 inactivation results in placental anomalies due to trophoblast cell proliferation and differentiation defects leading to severe delays in the development of placenta and causing the death of the embryo. Although Mek2(-/-) mutant mice survived without any apparent phenotype, double heterozygous Mek1(+/-)Mek2(+/-) mutants die during gestation from placental malformations. Together, these data emphasize the crucial role of the ERK/MAPK cascade in the formation of extraembryonic structures.

The blood-brain barrier (BBB) is the main interface controlling the exchange of nutrients and drugs between the blood and brain. Its specificity is given by some specific properties of the endothelium of the brain capillaries. They include the presence of tight junctions sealing adjacent endothelial cells and the absence of fenestrations preventing paracellular transport pathway across the BBB. The BBB is also a metabolic and pharmacological barrier because of the activity of many cytosolic enzymes and transporters expressed both or either at the luminal or abluminal faces of the brain microvessel endothelial cells. Macromolecules like insulin, leptin and transferrin may cross the BBB via receptor mediated transcytosis. More recently the discovery of P-glycoprotein, an ABC protein, at the luminal membrane of the brain endothelial cells has shown that several lipophilic antimitotic and psychotropic drugs are pumped out of the brain by this transporter. All these properties illustrate how complex the exchanges of nutrients and drugs across the BBB are.

To evaluate the use of intravenous vitreous fluorophotometry in assessment of the blood-aqueous barrier in eyes with uveal melanoma.Vitreous fluorophotometry was performed before treatment in 14 patients with uveal melanoma. Both eyes of patients were examined, and fifteen control healthy patients were examined between November 1996 and December 1996 at the department of ophthalmology of Bicêtre hospital.Tumors with height6 mm and serous retinal detachments were accompanied by marked alterations of the blood-aqueous barrier, vitreous fluorophotometry showed diffusion of dye in posterior, mid and anterior vitreous: 2.99 ng/ml in the posterior vitreous and 5.20 ng/ml in the anterior vitreous. The posterior vitreous fluorescence at 60 minutes in the control eyes was 1.43 ng/ml and 1.30 ng/ml in the anterior vitreous. Diffusion of dye was present in the posterior vitreous in patients with tumor height less than 6 mm: 2.38 ng/ml (1.43 ng/ml in control eyes) at 60 minutes.Fluorophotometry provides a method for the assessment of the blood-aqueous ocular barrier in eyes with choroidal melanoma.

To prospectively evaluate use of the laser flare meter the inflammatory response after phacoemulsification with four different types of intraocular lenses.Measurements with the Kowa laser flare meter FC-500 were done before surgery and at 1, 6 and 21 days following standard phacoemulsification with corneal incision in 157 patients. The patients were randomized in four groups to receive HSM IOL (group I), foldable acrylic IOL (group II), foldable three-piece silicone (group III), and foldable single-piece silicone (group IV).Overall, mean flare values were increased at D1, and decreased rapidly to normal values at D21. Intragroup analysis showed a slight increase of flare value observed in the PMMA group (p = 0.0015) and silicone monobloc group (p = 0.001) at D21 compared to D0. There was no statistical difference found between D0 and D21 in the acrylic and the silicone three pieces groups. At D1, a significant increase of flare values was observed in the PMMA (28.9 ph/ms) and silicone three pieces (28.8 ph/ms) groups, as compared to silicone monobloc group (22 ph/ms). At D21, the acrylic group had a significantly lower mean value than PMMA and silicone monobloc groups. No statistical difference was observed between acrylic and three-piece silicone at D21.This study shows that the inflammation in the four groups was very low after phacoemulsification by a corneal incision and attempts to explain the impact of the incision length on the breakdown of blood-aqueous barrier.

First described in 1957, anterior segment ischemia (ASI) following extraocular muscle surgery for non paralytic or paralytic strabismus is a rare but serious complication. Systemic and anatomical risk factors can be identified and vesselsparing surgical techniques used. The aim of this study is to evaluate those changes in the anterior chamber that may indicate the presence of post-operative subclinical ASI.Pre- and 1 day post-operative anterior chamber flare measurements with the Laser flare cell meter (Kowa FC-1000) were made in 107 patients (109 operations) undergoing strabismus surgery. Surgery was carried out by the same surgeon in all cases and under general anaesthesia. Patients were divided into different groups according to the muscles operated (horizontal recti, vertical recti, obliques, or combinations thereof).Global and selective analysis showed no significant statistical difference between pre- and post-operative flare measurements in patients undergoing strabismus surgery.No subclinical ASI was found in this study of 109 strabismus operations (107 patients).

The lacrimal film contains 6 to 10 g/l of proteins, 99% of which locally synthesized by the lacrimal glands. The study of these proteins allows us to explore the lacrimal function and to reveal an inflammatory process.The lacrimal proteinic profile included the determination of total proteins and electrophoresis on agarose gel and, if necessary, specific determinations of albumin, lactoferrin, lysozyme and immunoglobulins using a nephelemetric technique. Normal values were established on a hundred of individual tears.The electrophoretic proteinic profile may present different abnormalities, such as an inflammatory process, a functional alteration of the lacrimal glands or a dysproteinic abnormality of the tears. The specific determination of the principal lacrimal proteins allows us to accurately quantify each of them.The electrophoresis of the tears on an agarose gel reveals the presence of an inflammatory process or the quantitative or qualitative alteration of the lacrimal function. The immuno-nephelemetric determination of the most important proteins which are involved in theses mechanisms gives an accurate quantitative measurement of proteins and allows biological follow-up of the disease.

The immunological status of the eye, like the one of the brain, is generally considered as an "immune privilege" site because of the presence of a strong blood-ocular barrier, the lack of lymphatic drainage and, last but not the least, the absence of professional antigen-presenting cells. This dogma is now challenged by recent studies indicating that presentation of endogenous (as in autoimmune uveitis) or exogenous (like in ocular cysticercosis) antigens occurs. The local immune response seems regulated by active immunosuppressive mechanisms, in order to limit the destructive effect of inflammatory reactions.