Pharmacological regulation of SPARC by lovastatin in human trabecular meshwork cells.

PURPOSE: Statins have been shown to increase aqueous outflow facility. The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is a critical mediator of aqueous outflow and intraocular pressure (IOP). Here, we examine the effects of lovastatin on SPARC expression in trabecular meshwork (TM) cells, exploring the molecular mechanisms involved. METHODS: Primary cultured human TM cells were incubated for 24, 48, and 72 hours with 10 µM lovastatin. In separate cultures, media was supplemented with either farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) for the duration of the 72-hour time point experiment. Trabecular meshwork cells were also pretreated for 24 hours with lovastatin followed by 24-hour stimulation with 3 ng/mL TGF-ß2. Cell lysates and media were harvested and relative mRNA and protein level changes were determined. Krüppel-like factor 4 (KLF4) localization in normal human anterior segments was examined by immunofluorescence. Adenovirus expressing human KLF4 was used and relative changes in SPARC mRNA and protein levels were assessed. RESULTS: Incubating TM cells with lovastatin suppressed SPARC mRNA and protein levels. This effect was reversed upon media supplementation with GGPP but not FPP. Pretreating cells with lovastatin inhibited TGF-ß2 induction of SPARC. The KLF4 transcription factor was expressed throughout the TM and the inner and outer walls of Schlemm's canal. Lovastatin treatment upregulated KLF4 mRNA and protein levels. Overexpression of KLF4 downregulated SPARC expression. CONCLUSIONS: Collectively, our data identify lovastatin as an important pharmacological suppressor of SPARC expression in TM cells, and provide further insight into the molecular mechanisms mediating statin enhancement of aqueous outflow facility.

Long-term complications of iris-claw phakic intraocular lens implantation in Weill-Marchesani syndrome.

PURPOSE: This study was designed to report the long-term complications of iris-claw phakic intraocular lens implantation in a patient with Weill-Marchesani syndrome. METHODS: Case report and literature review. RESULTS: A 26-year-old man with a history of glaucoma had bilateral phakic lens implantation for high myopia 10 years previously. Two years later, the left implant dislocated and was repositioned. Slit-lamp examination of both eyes revealed phakic implants of the iris-claw variety. There were moderate iridocorneal adhesions in the areas in which the lens haptics pinched the iris in both eyes and moderate epithelial and stromal edema over the temporal one-third of the left cornea. The crystalline lenses were clear with 3+phacodonesis OU. Dilated fundus examinations revealed bilateral severe optic nerve cupping. Crystalline lens diameters were measured at 7.5mm in the right eye and 8 mm in the left. Anterior chamber depths were 2.63 mm OD and 2.40 mm OS. Specular microscopy revealed central endothelial cell counts of 1133 and 587 cells/mm OD and OS, respectively. Axial lengths were 23.3 mm OD and 25 mm OS. Gonioscopic examination revealed bilateral angle closure with marked peripheral anterior synechiae. Based on our findings of short stature, shortened and thickened fingers, relatively normal axial length, microspherophakia, high myopia, and glaucoma, we diagnosed the patient with Weill-Marchesani syndrome. CONCLUSION: Iris claw-lens phakic lenses may be an effective surgical alternative to correct high myopia in select patients; however, it may produce long-term complications in eyes with specific features.

Prevalence of the use of complementary and alternative medicine for glaucoma.

OBJECTIVES: To estimate the prevalence of complementary and alternative medicine (CAM) for glaucoma, explore possible demographic and disease-related associations, and inquire about the perceived benefit of these treatments. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: One thousand twenty-seven consecutive patients from two urban, referral glaucoma practices. MAIN OUTCOME MEASURE: Use of CAM specifically for glaucoma. RESULTS: The response rate was 97.4%. The percentage of people reporting use of CAM for glaucoma was 5.4% (54 of 1000 subjects) with 32 of these 54 (59%) having used more than one type. The percentages of those using the various types of nontraditional medicine were: megavitamin therapy (62.9%), herbal therapy (57.4%), exercise (24.0%), diet modification (22.2%), meditation, (1.8%), acupuncture (1.8%), faith healing (1.8%), and homeopathic remedies (1.8%). Patients who used CAM were more likely to be educated beyond high school (P = 0.0014) and less likely to be retired (P = 0.0053). Use of nontraditional therapy was not strongly associated with race (P = 0.044), age (P = 0.062), gender (P = 0.24), length of diagnosis (P = 0.91), or number of glaucoma medications (P = 0.58). Of those using nontraditional therapy, 52% believed that it was helpful, 39% were unsure, and 9% considered it not helpful; 72% discussed their use with an ophthalmologist. Seventy percent discovered it from sources other than providers of either traditional or nontraditional care. CONCLUSIONS: The prevalence of CAM use for glaucoma was 5.4% (95% confidence interval, 4.0%--6.4%). Most glaucoma patients currently cared for by ophthalmologists do not use nontraditional medicine.