Gene therapy of the cornea shows promise for modulating corneal transplant rejection but the most appropriate vector for gene transfer has yet to be determined. We investigated a lentiviral vector (LV) for its ability to transduce corneal endothelium. A lentivector expressing enhanced yellow fluorescent protein (eYFP) under the control of the Simian virus type 40 early promoter (LV-SV40-eYFP) transduced 80-90% of rat, ovine and human corneal endothelial cells as detected by fluorescence microscopy. The kinetics of gene expression varied among species, with ovine corneal endothelium showing a relative delay in detectable reporter gene expression compared with the rat or human corneal endothelium. Vectors containing the myeloproliferative sarcoma virus promoter or the phosphoglycerate kinase promoter were not significantly more effective than LV-SV40-eYFP. The stability of eYFP expression in rat and ovine corneas following ex vivo transduction of the donor cornea was assessed following orthotopic corneal transplantation. Following transduction ex vivo, eYFP expression was maintained in corneal endothelial cells for at least 28 days after corneal transplantation in the sheep and 460 days in the rat. Thus, rat, ovine and human corneal endothelial cells were efficiently transduced by the LV, and gene expression appeared stable over weeks in vivo. Gene Therapy (2007) 14, 760-767.

Although lentiviral vectors show some promise for corneal gene therapy, they are less efficient than adenoviral vectors.

The Crystalens HD showed some benefit for intermediate visual function compared to the monofocal IOLs with both groups wearing full correction for distance. There were no significant signs of accommodation in either group.

Ptosis and lower lid margin eversion are previously unreported findings in patients with MEN2B. Medullary thyroid carcinoma is the most serious consequence of MEN2B and has a high mortality if untreated. Early diagnosis and prophylactic thyroidectomy may be lifesaving. Gene mutations can be identified but the sporadic tendency of the syndrome emphasizes the importance of early clinical detection. MEN2B is one of a number of systemic malignancies with ophthalmic manifestations. Ophthalmologists should be aware of the external features of this rare but lethal malignancy.

The GRE5 promoter in a lentiviral vector drove rapid, sustained and inducible transgene expression in both ovine and human corneas in the presence of dexamethasone. A steroid-inducible promoter may be useful for controlling transgene expression in gene-modified donor corneal allografts.