MUC1 is a novel regulator of ErbB1 receptor trafficking.

ErbB receptors are key regulators of cell survival and growth in normal and transformed tissues. The oncogenic glycoprotein MUC1 is a binding partner and substrate for erbB1 and MUC1 expression can potentiate erbB-dependent signal transduction. After receptor activation, erbB1 is typically downregulated via an endocytic pathway that results in receptor degradation or recycling. We report here that MUC1 expression inhibits the degradation of ligand-activated erbB1. Through the use of both RNAi-mediated knock down and overexpression constructs of MUC1, we show that MUC1 expression inhibits erbB1 degradation after ligand treatment in breast epithelial cells. This MUC1-mediated protection against erbB1 degradation can increase total cellular pools of erbB1 over time. Biotinylation of surface proteins demonstrates that cell-surface associated erbB1 receptor is protected by MUC1 against ligand-induced degradation, although this is accompanied by an increase in erbB1 internalization. The MUC1-mediated protection against degradation occurs with a decrease in EGF-stimulated ubiquitination of erbB1, and an increase in erbB1 recycling. These data indicate that MUC1 expression is a potent regulator of erbB1 receptor stability upon activation and may promote transformation through the inhibition of erbB1 degradation.

[Inadvertent intravitreal lidocaine injection following subcutaneous palpebral anesthesia: retinal toxicity of lidocaine?]. / Injection intravitréenne accidentelle de lidocaïne au cours d'une anesthésie palpébrale: toxicité rétinienne de la lidocaïne?

INTRODUCTION: We report an atypical case of scleral perforation due to an inadvertent intravitreal lidocaine injection following palpebral anesthesia. We discuss the management of this rare complication and focus on the transient lidocaine toxicity on human retina. OBSERVATION: A 29-year-old man presented with unilateral decreased vision during a lower right palpebral anesthetic injection for a chalazion removal procedure. The patient's vision was light perception. Examination revealed intraocular pressure at 55 mmHg, a wound of the posterior crystalloid, an intraocular gas bubble, and a central retinal artery spasm. On ERG, the b wave was decreased. The central retinal artery spasm resolved with prompt reduction of hypertony. Twenty-four hours later, the vision was 6/10 and the ERG showed an increased b wave activity. No clinical retinal toxicity of lidocaine was observed. Only a subcapsular cataract was observed, which had caused the loss of vision. CONCLUSION: This case confirms that lidocaine is well tolerated by the retina and reminds us that superficial palpebral anesthetic injection should be done with great caution.

Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-alpha soluble receptor in uveitis.

Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.

[The use of liposomes as intravitreal drug delivery system]. / Administration intra-vitréenne de liposomes pour la vectorisation de principes actifs.

Liposomes are vesicular lipidic systems allowing encapsulation of drugs. This article reviews the relevant issues in liposome structure (composition and size), and their influence on intravitreal pharmacokinetics. Liposome-mediated drug delivery to the posterior segment of the eye via intravitreal administration has been addressed by several authors and remains experimental. Liposomes have been used for intravitreal delivery of antibiotics, antivirals, antifungal drugs, antimetabolites, and cyclosporin. Encapsulation of these drugs within liposomes markedly increased their intravitreal half-life, and reduced their retinal toxicity. Liposomes have also shown an attractive potential for retinal gene transfer by intravitreal delivery of plasmids or oligonucleotides.

[Why are aphakic anterior chamber intraocular lenses still implanted? Five-year incidence and implantation circumstances at the Hôtel-Dieu in Paris]. / Pourquoi pose-t-on encore des implants de chambre antérieure à support angulaire chez l'aphaque? Incidence et circonstances des implantations sur 5 ans à l'Hôtel-Dieu de Paris.

PURPOSE: To report incidence and circumstances of aphakic anterior chamber intraocular lens implantation. METHODS: Retrospective study of medical charts of anterior chamber intraocular lens implantation in the Ophthalmology Department, Hôtel Dieu, Paris, from 1996 to 2000, investigating the number of anterior intraocular lenses (ACIOL) implanted, circumstances, and incidence during cataract extraction. RESULTS: One hundred and forty-three ACIOLs (139 patients, 60 men, 79 women) were implanted. The mean age was 75.98+/-10.6 years [range, 35-96 years]. All ACIOLs were of open-loop design: open C-loop or Kelman lens. Four circumstances leading to ACIOL implantation were reported: extracapsular cataract extraction with intraoperative complications (94 cases), intracapsular cataract extraction (13 cases), secondary implantation (20 cases), and penetrating keratoplasty with ACIOL (9 cases). Since 1996, the number of ACIOLs implanted each year has decreased (p<0.01): 1.09% of cataract extractions performed in 1996 were implanted with ACIOLs and 0.43% in 2000. At the end of the 5-year period, 12,580 cataract extractions had been performed in our department, with a mean incidence of ACIOL implantation at 0.85%. CONCLUSION: ACIOLs continue to be implanted in some cases in the absence of capsular support. Because of endothelial complications, they must be reserved for elderly patients. Endothelial surveillance using specular microscopy remains indispensable.

[Corneal graft rejection and corticoid iontophoresis: 3 case reports]. / Rejet de greffe et iontophorèse de corticoïdes: à propos de 3 cas.

This is the first report of three cases of severe acute corneal graft rejection, treated by transscleral methylprednisolone (Solumédrol) iontophoresis. The efficacy of the treatment was evaluated by corneal transparency, visual acuity and corneal inflammation parameters. The patient was treated with Solumédrol iontophoresis once a day for 3 days with a topical corticotherapy reduced to three drops of dexamethasone per day. Iontophoresis was performed, under topical anesthesia, and lasted 3 minutes with a 1.5-mA current. The subjective and objective tolerance of iontophoresis was good. No side-effect was observed. Corneal transparency and visual acuity improved rapidly after the second iontophoresis procedure. These observations show that Solumédrol iontophoresis might be an alternative to pulse therapy in the treatment of corneal graft rejection. Further comparative studies are necessary to confirm these preliminary observations.

Adventitial sheathotomy for decompression of recent onset branch retinal vein occlusion.

UNLABELLED: Interesting results have been reported on the use of pars plana vitrectomy with adventitial sheathotomy for the decompression of branch retinal vein occlusions (BRVO). Recent onset BRVO responsible for a visual acuity of 20/40 or less have been estimated to be good candidates for this procedure. We report on the results of the prospective evaluation of three eyes (in three patients) with recent onset BRVO which underwent surgical decompression. Three men, aged 40, 50, and 68 years presenting with BRVO for 4, 4, and 3 weeks respectively, underwent surgical decompression. Initial visual acuity was 20/80, 20/80, and 20/200. After 11, 10, and 9 months follow-up, visual acuity was 20/80, 20/200, and 20/200. In two eyes, an increase of the area of retinal non-perfusion was treated with peripheral laser photocoagulation. No cataract, retinal tears or retinal detachment were observed. CONCLUSION: although feasible, sheathotomy did not lead to a significant visual improvement in our patients. Dissection of the arteriovenous crossing could have induced vascular trauma. Furthermore, vitrectomy with posterior hyaloid detachment alone could be of benefit in the treatment of branched retinal vein occlusions. A prospective randomised trial is needed to assess the effectiveness and the safety of this procedure and to determine the best candidates for surgery.