Biomedical subjects
Publications and source records attributed to J Timothy Stout.
Retinopathy of prematurity (ROP) is a relatively new condition. Only in the last 60 years have children survived who were born prematurely enough to have a significantly immature retinal vasculature. This article describes the classification and physiology of ROP, the interventions now available, and possible future therapies.
PURPOSE: To test whether lentivirus-mediated expression of an endostatin::kringle-5 (E::K-5) fusion gene has an inhibitory effect on neovascularization and failure of corneal transplants. METHODS: A lentiviral vector containing a fusion transgene comprising the human endostatin gene and the kringle-5 domain of the human plasminogen gene (E::K-5) was used for transduction of corneal buttons ex vivo. The corneal buttons were transplanted after overnight incubation in media containing either lentivirus or PBS. Sixteen rabbits underwent allogenic penetrating keratoplasty in one eye. The area of neovascularization from the limbus to within the graft was documented after surgery. RT-PCR was performed to demonstrate the presence of transgene mRNA within the graft. Histopathology was used to analyze neovascularization, inflammation, and rejection morphology. RESULTS: Less neovascularization was observed in corneas treated with the lentivirus E::K-5 fusion vector. Early onset and profound neovascularization was observed in control eyes. E::K-5-treated animals did not have graft failure, whereas five of the six control animals had graft failure, as classified by opacification of the graft. All E::K-5 transduced corneas tested were positive by RT-PCR for the unique fusion gene sequence. Histopathology corroborated a significant increase of blood vessel presence and inflammatory reaction in control compared with treated eyes. CONCLUSIONS: Corneas transduced with a lentivirus containing an endostatin::kringle-5 fusion gene demonstrated an inhibition of neovascularization and graft failure. E::K-5 gene transduction through a lentiviral vector system may be a useful adjunct to prevent graft neovascularization and corneal graft rejection in high-risk corneal transplants with antecedent rejection or neovascularization.
OBJECTIVE: To demonstrate the progression of electroretinographic (ERG) findings in mucolipidosis IV. METHODS: Two patients with mucolipidosis IV were examined clinically and their condition was followed up for ophthalmic manifestations of the disease. Electroretinograms were performed on both patients, and conjunctival biopsy specimens were analyzed for characteristic ultrastructural inclusion bodies using light and electron microscopy. Genomic DNA isolated from peripheral blood was screened for 2 major founder mutations in the ML4 gene using polymerase chain reaction and restriction fragment length polymorphism analyses. Haplotypes were confirmed by automated sequencing of polymerase chain reaction products. RESULTS: In patient 1, an ERG obtained at 12 months of age showed mildly subnormal amplitude of rod-mediated and cone-mediated responses and significantly prolonged rod and cone b-wave implicit times. An ERG obtained when the patient was 6.6 years old disclosed marked progression with greater loss of b-wave than a-wave responses to rod-and-cone-mediated activity. Scotopic ERG at the highest intensity was electronegative in configuration. In patient 2, ERG showed minimal rod-mediated responses, severely subnormal cone-mediated responses, and prolonged cone b-wave implicit times. Again, electronegative configuration of the scotopic bright flash response indicated greater disturbance of b-wave generators. CONCLUSIONS: Novel ERG findings in 2 cases of mucolipidosis IV are reported with associated clinical courses, histopathologic abnormality, and genetic studies. In both cases ERGs demonstrate an electronegative configuration, suggesting that the primary retinal disturbance in mucolipidosis IV may occur at or proximal to the photoreceptor terminals.