Aqueous misdirection syndrome: clinical outcomes and risk factors for treatment failure.

PURPOSE: To evaluate the outcomes of postoperative aqueous misdirection and factors predicting failure of interventions. METHODS: This retrospective study included 49 eyes from 47 patients with aqueous misdirection following glaucoma or cataract surgery. Resolution of aqueous misdirection (AM) was deepening of the central anterior chamber (AC) and intraocular pressure (IOP) ≤ 21 mmHg. The Cox proportional hazards regression model was used to evaluate risk factors for failure of various treatments. RESULTS: 10/49 eyes (20%) resolved with conservative management, and 39/49 eyes (80%) needed multiple intervention, of which 95% (37/39) eyes achieved resolution of aqueous misdirection. Pseudophakia predicted the need for multiple interventions with a hazard ratio of 2.391 (1.158-4.935), p = 0.02). Among the risk factors assessed for resolution of AM, longer axial length (HR: 0.61 (0.414-0.891), p < 0.01) and eyes with prior glaucoma surgery predicted resolution (HR: 0.142 (0.027-0.741), p < 0.01) and delayed presentation predicted failure (HR: 1.002 (1.0002-1.0031), p < 0.02). CONCLUSION: Pseudophakic eyes were more refractory and predicted the need for multiple interventions. Eyes with prior glaucoma surgery and those with longer axial length had achieved resolution faster, and delayed presentation was a risk factor for failure to resolve.

Glaucoma Mimickers: A major review of causes, diagnostic evaluation, and recommendations.

Background: Glaucoma is characterized by chronic progressive optic neuropathy with corresponding visual field changes, with or without raised intraocular pressure (IOP). When diagnosing glaucoma or monitoring its progression, the examiner has to rely on the appearance of the optic disc, characteristic retinal nerve fiber layer defects, and corresponding visual field defects. However, similar changes and symptoms may be observed in several other disorders of the optic nerve and retina that may mimic glaucoma, often leading to misdiagnosis. Methods and result: The consequences of misdiagnosis not only result in improper treatment that may impact vision but also would negatively affect the overall health, psychological well-being of the patient, and may have considerable economic implications.Conclusion: The current review describes various conditions that mimic glaucoma and the features that help differentiate these conditions from glaucoma.

Insoluble protein characterization by circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR).

Besides misfolded proteins, which still retain the capacity to fold into uniquely defined structures but are misled to "off-pathway" aggregation, there exists a group of proteins which are unrefoldable and insoluble in buffers. Previously no general method was available to solubilize them and consequently their solution conformations could not be characterized. Recently, we discovered that these insoluble proteins could in fact be solubilized in pure water. Circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) characterization led to their classification into three groups, all of which lack the tight tertiary packing and consequently anticipated to unavoidably aggregate in vivo with ~150 mM ions, thus designated as "intrinsically insoluble proteins (IIPs)." It appears that eukaryotic genomes contain many "IIP," which also have a potential to interact with membranes to trigger neurodegenerative diseases. In this chapter, we provide a detailed procedure to express and purify these proteins, followed by CD and NMR spectroscopy characterization of their conformation and interaction with dodecylphosphocholine (DPC).

VAPC, an human endogenous inhibitor for hepatitis C virus (HCV) infection, is intrinsically unstructured but forms a "fuzzy complex" with HCV NS5B.

Nearly 200 million people are infected by hepatitis C virus (HCV) worldwide. For replicating the HCV genome, the membrane-associated machinery needs to be formed by both HCV non-structural proteins (including NS5B) and human host factors such as VAPB. Recently, the 99-residue VAPC, a splicing variant of VAPB, was demonstrated to inhibit HCV replication via binding to NS5B, thus acting as an endogenous inhibitor of HCV infection. So far, the structure of VAPC remains unknown, and its interaction with NS5B has not been biophysically characterized. In this study, we conducted extensive CD and NMR investigations on VAPC which led to several striking findings: 1) although the N-terminal 70 residues are identical in VAPC and VAPB, they constitute the characteristic ß-barrel MSP fold in VAPB, while VAPC is entirely unstructured in solution, only with helical-like conformations weakly populated. 2) VAPC is indeed capable of binding to NS5B, with an average dissociation constant (Kd) of ∼20 µM. Intriguingly, VAPC remains dynamic even in the complex, suggesting that the VAPC-NS5B is a "fuzzy complex". 3) NMR mapping revealed that the major binding region for NS5B is located over the C-terminal half of VAPC, which is composed of three discrete clusters, of which only the first contains the region identical in VAPC and VAPB. The second region containing ∼12 residues appears to play a key role in binding since mutation of 4 residues within this region leads to almost complete loss of the binding activity. 4) A 14-residue mimetic, VAPC-14 containing the second region, only has a ∼3-fold reduction of the affinity. Our study not only provides critical insights into how a human factor mediates the formation of the HCV replication machinery, but also leads to design of VAPC-14 which may be further used to explore the function of VAPC and to develop anti-HCV molecules.