RESUMO
Neurotrophic keratitis represents a complex degeneration of the cornea that can result in debilitating symptoms and serious sight-threatening complications. Patients with neurotrophic keratitis (NK) usually present with a history of corneal injury or past surgical intervention involving damage to the corneal nerves; as well as, chronic ocular surface disease. This nerve damage results in sensory loss and poor healing to the corneal tissues. This poor ability to heal results in the downward spiral of events that NK patients are subject to, which can include corneal surface breakdown, ulceration, melting, and total perforation. Treatments to attempt to support the cornea to heal and then protect it have recently advanced beyond traditional treatments and may include amniotic membrane application, autologous serum eye drops, biologic eye drops, and various other supportive treatments. Even aggressive combinations of these, and many other treatments, can leave NK patients still uncontrolled and progressing to end-stage disease that would require invasive intervention resulting in an even worse prognosis. This case report describes a patient who demonstrated all three stages of NK. Multiple interventions were initiated, including tarsorrhaphy, autologous serum eye drops, Prokera amniotic membrane, antibiotics, bandage contact lenses (BCL) therapy, and PKP. However, the patient experienced variable and transient improvement with relapse within a few weeks with recurrent and persistent epithelial erosion and stromal ulceration. A novel eye drop, cenegermin (OXERVATETM), an ophthalmic solution containing 20 µg/mL of a recombinant form of human nerve growth factor (NGF), was added to her treatment regimen allowing for successful management of NK and restoration of corneal integrity.
RESUMO
PURPOSE: Oxidative damage is a major factor causing cataracts, which account for almost half of human blindness cases worldwide. In this study, we wished to determine if overexpression of superoxide dismutase (SOD) in intact lenses could prevent cataract formation induced by oxidative stress. METHODS: Fresh, intact lenses from 6-week-old male/female Sprague Dawley rats were incubated with plasmid DNA encoding the human SOD1 (Cu/Zn-SOD) gene at 37 degrees C in a CO2 cell culture chamber with 95% air and 5% CO2. SOD1 expression was determined by western blotting and SOD enzyme activity. Lenses with or without overexpression of SOD1 were treated with H2O2 and cataract formation was examined. SOD1 regulation of protein kinase Cgamma (PKCgamma) was determined by PKCgamma enzyme activity assay. Intact lens gap junctions were determined by dye transfer assay. RESULTS: In the lens overexpression system, SOD1 cDNA was fused to EYFP to generate EYFP:SOD1 fusion proteins which allow detection from endogenous SOD1. Incubation of intact lenses with plasmid DNA produced EYFP:SOD1 fusion proteins as determined by western blot using anti-GFP or anti-SOD1 antibodies. This caused significant increases in SOD enzyme activity. Data indicated that SOD1 plasmid DNA can be expressed as a functional enzyme in intact lenses in culture. Lenses overexpressing SOD1 remained clear after H2O2 treatment at 100 muM for 24 h, similar to control. Overexpression of SOD1 diminished the effect of H2O2 on PKCgamma activation and subsequent inhibition of gap junctions, indicating that overexpression of SOD1 may reduce reactive oxygen species (ROS) production, and this would prevent the normal H2O2 effect on cataract formation. CONCLUSIONS: Overexpression of SOD1 in whole lens prevents H2O2-induced oxidative damage (cataract formation) to the lens and subsequent control of gap junctions by protein kinase Cgamma.
