Long term effect of trabeculectomy on retrobulbar haemodynamics in glaucoma.

PURPOSE: Previous reports showed increased flow velocities in retrobulbar vessels after glaucoma surgery in the first weeks. Colour Doppler imaging was performed to investigate the long-term effects of trabeculectomy on retrobulbar haemodynamics in patients with primary open-angle glaucoma (POAG). METHODS: In a prospective study 30 patients (mean age 63.2 ± 15.4 years) with POAG were included. Colour Doppler imaging was performed before 1-2 weeks, after 2 months, after 4-6 months, and up to 3 years after trabeculectomy to determine the peak systolic and end-diastolic velocities in the ophthalmic artery, central retinal artery, and the short nasal and temporal posterior ciliary arteries. RESULTS: Mean follow-up was 416 ± 246 days. In the first postsurgical period mean intraocular pressure (IOP) decreased after trabeculectomy from 25 ± 6 mmHg to 9 ± 4 mm Hg (p < 0.0001) and then increased in the further follow-up to 13 ± 3 mmHg (p < 0.05) without any anti-glaucomatous medication. Colour Doppler imaging revealed a significant increase of the end-diastolic velocities of the central retinal artery at all postoperative visits compared to pre-surgery (p < 0.003) and of the end-diastolic velocities in the temporal posterior ciliary arteries (p < 0.003). The change of blood flow parameters that increased during follow-up was significantly correlated to the change in ocular perfusion pressure and IOP. CONCLUSIONS: End-diastolic velocities of the central retinal artery and of the temporal posterior ciliary arteries increased after successful trabeculectomy and remained stable in a longer period - even if IOP rose significantly in the follow-up.

Uridine abrogates mitochondrial toxicity related to nucleoside analogue reverse transcriptase inhibitors in HepG2 cells.

OBJECTIVE: To assess in vitro if uridine may be suitable to prevent or treat mitochondrial toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTIs). METHODS: Human HepG2-hepatocytes were exposed to NRTIs with or without uridine for 25 days. Cell growth, lactate production, intracellular lipids, mitochondrial DNA (mtDNA) and the ratio between the respiratory chain components COX II (mtDNA-encoded) and COX IV (nuclear-encoded) were measured. RESULTS: HepG2 cells exposed to zalcitabine (177 nM) without uridine developed a severe depletion of mtDNA (to 8% of wild-type mtDNA levels), resulting in a decline of cell proliferation and COX II levels, with increased lactate and lipid accumulation. Uridine fully abrogated the adverse effects of zalcitabine on hepatocyte proliferation and normalized lactate synthesis, intracellular lipids and COX II levels by adjusting mtDNA levels to about 65% of NRTI-unexposed control cells. This effect was dose-dependent, with a maximum at 200 microM of uridine. Uridine also rapidly and fully restored cell function when added to cells with established mitochondrial dysfunction (zalcitabine for 15 days) despite continued zalcitabine exposure. Uridine also normalized cell proliferation in HepG2 cells exposed to 36 microM of stavudine and protected HepG2-cells exposed to 7 microM of zidovudine + 8 microM of lamivudine (pyrimidine analogues), but failed to improve cell function or mtDNA in cells exposed to 11.8 or 118 microM of didanosine (a purine analogue). CONCLUSIONS: The pyrimidine precursor uridine may attenuate the mitochondrial toxicity of antiretroviral pyrimidine NRTIs in vitro, and its supplementation may represent a promising strategy in the prevention or treatment of mitochondrial toxicities in HIV-infected patients.