Sorting nexins (SNXs) form a family of proteins known to interact with components in the endosomal system and to regulate various steps of vesicle transport. Sorting nexin 9 (SNX9) is involved in the late stages of clathrin-mediated endocytosis in non-neuronal cells, where together with the GTPase dynamin, it participates in the formation and scission of the vesicle neck. We report here crystal structures of the functional membrane-remodeling unit of SNX9 and show that it efficiently tubulates lipid membranes in vivo and in vitro. Elucidation of the protein superdomain structure, together with mutational analysis and biochemical and cell biological experiments, demonstrated how the SNX9 PX and BAR domains work in concert in targeting and tubulation of phosphoinositide-containing membranes. The study provides insights into the SNX9-induced membrane modulation mechanism.

Purpose: To retrospectively evaluate the efficacy and safety of all transscleral cyclophotocoagulation (TCP) treatments performed during a 5-year period. Methods: Medical records of all patients, who had undergone TCP treatment between 2010 and 2014 at Ume a University Hospital, Sweden, were evaluated. Clinical data including intraocular pressure (IOP), visual acuity (VA), number of topical glaucoma medications, use of oral acetazolamide, retreatments and complications during a 2-year follow-up were registered. Global success was defined as IOP 6-18 mmHg with or without glaucoma medication. Results: Three hundred patients underwent TCP during the time period. Mean IOP at baseline was 29.3 AE 11.0 (mean AE standard deviation) mmHg (n = 297) with a mean reduction of 11.5 (AE12.0) mmHg at 1 year (n = 258; p < 0.001) and 12.6 (AE12.0) mmHg at 2-year follow-up (n = 245; p < 0.001). Global success at 2 years was 64%, achieved by a mean of 1.2 treatments (n = 257). The number of topical glaucoma medications at baseline was 3.1 (AE1.0; n = 296) and was reduced by 0.9 (AE1.0) medications at 2 years (n = 244; p < 0.001). Use of oral acetazolamide decreased from 30% (n = 90) at baseline to 5.3% (n = 13) at 2 years. In eyes with Snellen VA ≥ 0.1, the mean VA at baseline was 0.55 (AE0.3) logarithm of the minimum angle of resolution (logMAR; n = 132) and 1.1 (AE0.9) logMAR (n = 76) at 2 years (p < 0.001). No cases of phthisis bulbi were found. Conclusion: This study displays a substantial and long-term reduction of IOP following TCP with a decrease in topical and oral glaucoma medications. The treatment appears to be safe but the decrease in VA during follow-up is a concern that needs further evaluation.

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To evaluate the intraocular pressure (IOP)-lowering effect of laser trabeculoplasty (LTP) in eyes which IOP had been substantially reduced by intensive topical treatment for one week. Methods: Patients with newly diagnosed open-angle glaucoma were randomized to treatment with three IOP-lowering substances. One week later, 360°argon or selective LTP was performed. IOP was measured before LTP and at one-, three-, six-and 12-month post-LTP. The patients were part of the Glaucoma Intensive Treatment Study (GITS). Results: Mean IOP (AE SD) in 152 eyes of 122 patients was 14.0 (AE 3.5) mmHg just before LTP. For every mmHg higher IOP prior to LTP, the IOP was reduced by an additional 0.6 mmHg at 12 months. The IOP was significantly reduced at all follow-up visits from À2.6 (AE 3.1) mmHg at one month to À2.1 (AE 3.8) mmHg at 12 months in eyes with pre-LTP IOP ≥ 15 mmHg, while no significant IOP reduction was seen in eyes with pre-LTP IOP < 15 mmHg. Older age, argon LTP and male sex were associated with larger IOP reduction after 12 months, whereas presence of exfoliation syndrome was associated with a smaller IOP reduction. No severe complications were reported. Conclusion: Success of LTP was highly dependent on the IOP level prior to LTP treatment. A sustained significant IOP reduction was seen in eyes with pre-LTP IOP ≥ 15 mmHg whereas no such effect was seen in eyes with pre-LTP IOP < 15 mmHg. Thus, LTP can be considered in eyes with multi-treatment when target pressure of < 15 mmHg is not achieved.

PurposeTo evaluate the long‐term effect of laser trabeculoplasty (LTP) in patients randomized to multi‐treatment in the Glaucoma Intensive Treatment Study (GITS).MethodsPatients with untreated newly diagnosed open‐angle glaucoma were treated with three intraocular pressure (IOP)‐lowering substances for 1 week and then 360° argon or selective LTP was performed. IOP was measured just before LTP and repeatedly during the 60‐month study period. Our previous report on 12 months follow‐up data revealed no effect of LTP in eyes having an IOP <15 mmHg before the laser treatment.ResultsBefore LTP, the mean IOP ± standard deviation in all 152 study‐eyes of 122 multi‐treated patients was 14.0 ± 3.5 mmHg. Three eyes of three deceased patients were lost to follow‐up during the 60 months. After exclusion of eyes that received increased therapy during follow‐up, the IOP was significantly reduced at all visits up to 48 months in eyes with pre‐LTP IOP ≥15 mmHg; 2.6 ± 3.1 mmHg at 1 month and 1.7 ± 2.8 mmHg at 48 months, n = 56 and 48, respectively. No significant IOP reduction was seen in eyes with pre‐LTP IOP <15 mmHg. Seven eyes, i.e., <13%, with pre‐LTP IOP ≥15 mmHg at baseline had required increased IOP‐lowering therapy at 48 months.ConclusionLTP performed in multi‐treated patients may provide a useful IOP reduction that is maintained over several years. This was true on a group level when the initial IOP was ≥15 mmHg, but if the pre‐laser IOP was lower than that, chances of LTP success were small.