Abstract
Abstract: :
Purpose: To investigate the effect of α-tocopherol on retinal neovascularization in pigs caused by retinal branch vein occlusion (BVO), based on the hypothesis that tocopherol would inhibit neovascularization by inhibiting the ischemia-induced activation of protein kinase C (PKC). Methods: BVO was created in a standardized manner using photodynamic thrombosis with Rose Bengal dye and thermal burns from the argon green laser. α-Tocopherol was administered orally in two separate experiments. In the first experiment, tocopherol was administered to 2 groups(n=3 each) at average daily doses of 5 or 20 IU/kgBW for 3 1/2 months(equivalent to 350 and 1400 IU/day/70 kg human, respectively), and the therapy was begun on the day that the retinas were photocoagulated. Three BVO animals remained as untreated controls. In the second experiment, α-tocopherol therapy was initiated one month prior to photocoagulation, and only the higher dose of tocopherol was compared to controls (n=4 each). PKC activity was measured using an in situ radioactive method. The extent of neovascularization was assessed by semi-quantitative grading of the retinal vasculature based on microscopic evaluation of retinal whole mounts, gross evaluation of the extent of fluorescein leakage in fluorescein angiograms, and counting of pre-retinal vessels in tissue cross-sections. Results: PKC activity increased in control eyes following induction of ischemia, while in eyes from tocopherol-treated groups, PKC levels were significantly lower (p=0.01). Pre-retinal neovascularization developed adjacent to BVO sites in retinas within the control group, and these new vessels leaked large amounts of fluorescein. Compared to the untreated controls, unexpectedly, neither of the two doses of α-tocopherol inhibited the development of pre-retinal neovascularization. In fact, treated animals exhibited worse neovascularization scores (p=0.03). Conclusion: α-Tocopherol supplementation had the desired effect of inhibiting ischemia-induced activation of PKC, but did not inhibit ischemia-induced neovascularization.
Keywords: 483 neovascularization • 316 animal model • 615 vascular occlusion/vascular occlusive disease