In the endoplasmic reticulum (ER), a number of thioredoxin (Trx) superfamily proteins are present to enable correct disulfide bond formation of secretory and membrane proteins via Trx-like domains. ...Here, we identified a novel transmembrane Trx-like protein 4 (TMX4), in the ER of mammalian cells. TMX4, a type I transmembrane protein, was localized to the ER and possessed a Trx-like domain that faced the ER lumen. A maleimide alkylation assay showed that a catalytic CXXC motif in the TMX4 Trx-like domain underwent changes in its redox state depending on cellular redox conditions, and, in the normal state, most of the endogenous TMX4 existed in the oxidized form. Using a purified recombinant protein containing the Trx-like domain of TMX4 (TMX4-Trx), we confirmed that this domain had reductase activity in vitro. The redox potential of this domain (−171.5 mV; 30 °C at pH 7.0) indicated that TMX4 could work as a reductase in the environment of the ER. TMX4 had no effect on the acceleration of ER-associated degradation. Because TMX4 interacted with calnexin and ERp57 by co-immunoprecipitation assay, the role of TMX4 may be to enable protein folding in cooperation with these proteins consisting of folding complex in the ER.
Purpose
The purpose of this study was to determine the incidence of and risk factors for intraocular pressure (IOP) elevation within 24 h following vitrectomy for rhegmatogenous retinal detachment ...(RD).
Methods
We assessed 34 eyes of 34 consecutive patients with RD undergoing vitrectomy and 12 eyes of 12 patients with macular hole as controls. IOP was measured using Tonopen XL before surgery, at the end of surgery, and at 5 h and 1 day postoperatively. IOP at the end of surgery was adjusted to 15.0 ± 2.0 mmHg.
Results
IOP elevation was found in five RD eyes at 5 h and in 13 1 day postoperatively. IOP in patients with RD at both 5 h and 1 day postoperatively was significantly higher than that of controls. Circumferential dimension of retinal tears and disease duration were significantly associated with IOP elevation at both 5 h and 1 day postoperatively.
Conclusions
IOP elevation in the early postoperative period following vitrectomy for RD is common. The risk factors for IOP elevation include the extent of retinal tears and duration of detachment. Prophylactic treatment may be useful in eyes with higher risks of IOP elevation.
To evaluate prognostic factors for metamorphopsia in patients undergoing vitrectomy for epiretinal membrane using spectral domain optical coherence tomography.
This study included 53 eyes of 53 ...patients undergoing vitrectomy for idiopathic epiretinal membrane. The authors examined visual acuity, severity of metamorphopsia with M-CHARTS, and retinal microstructures with spectral domain optical coherence tomography before surgery and 3 months and 6 months after surgery. Central foveal thickness, parafoveal retinal thickness, macular volume, thickness of the ganglion cell layer, inner nuclear layer, and outer retinal layer (ONL + OPL: outer nuclear layer and outer plexiform layer) were analyzed using an image processing program. The status of the outer retinal lines was also evaluated.
Preoperative metamorphopsia score (M-score) significantly correlated with central foveal thickness, inner nuclear layer thickness, and ONL + OPL thickness. Postoperative M-score significantly correlated with postoperative central foveal thickness and inner nuclear layer thickness. Inner nuclear layer thickness had significant correlation with M-score at each time point by multiple regression analysis, whereas other parameters were not relevant. Multiple regression analysis showed that preoperative inner nuclear layer thickness yielded the highest regression coefficient with postoperative M-score.
Inner nuclear layer thickness was found to be a good indicator of metamorphopsia both before and after surgery and a predictor of postoperative metamorphopsia in patients with epiretinal membrane.
To investigate the relationship between the severity of metamorphopsia and the foveal microstructure measured with spectral-domain optical coherence tomography (SD-OCT) in patients with epiretinal ...membrane (ERM).
This study included 48 eyes of 48 patients with idiopathic ERM and 18 age-matched normal controls. We examined the logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and the severity of metamorphopsia using M-CHARTS. Central foveal thickness (CFT), central retinal thickness at the fovea (CRT-1mm) and parafovea (CRT-3mm), and macular volume (MV) were measured with SD-OCT software. Based on the obtained OCT image, we divided the 1.0 × 1.0-mm area centered on the fovea into nine sections and quantified the following parameters using an image-processing program: mean thickness of the ganglion cell layer (GCL), inner nuclear layer (INL), and outer retinal layer (ONL+OPL: outer nuclear layer and outer plexiform layer), the degree of the photoreceptor inner and outer segment junction (IS/OS), and external limiting membrane (ELM) disruption.
CFT, CRT-1mm, CRT-3mm, MV, mean GCL, INL, and ONL+OPL thickness were significantly larger in patients with ERM than in normal controls. Multiple regression analysis revealed that the severity of metamorphopsia was significantly related to the mean INL thickness (P < 0.0001). LogMAR BCVA had a significant correlation with the degree of IS/OS disruption (P < 0.05), whereas other parameters were not relevant.
In patients with idiopathic ERM, the degree of metamorphopsia is associated with INL thickness, and IS/OS status influences visual acuity.
We investigated the relationship between contrast sensitivity (CS) and vision-related quality of life (VR-QOL) in patients with central retinal vein occlusion following ranibizumab intravitreal ...injection; CS showed a stronger association with VR-QOL than visual acuity.
To investigate the relationship between CS, VR-QOL and optical coherence tomography (OCT) findings in patients with cystoid macular oedema secondary to central retinal vein occlusion (CRVO-CMO) following intravitreal injection of ranibizumab.
This was a multicentre, open-label, single-arm, prospective study. The study included 23 patients with CRVO-CMO who were followed up for 12 months after treatment. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS) and OCT images were obtained every month. For VR-QOL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was administered to the patients before treatment and at 3, 6 and 12 months following treatment.
The LCS and VFQ-25 composite score improved significantly from baseline to 12 months following treatment. The multiple regression analysis revealed that the LCS of the affected eye and BCVA of the fellow eye were related to the VFQ-25 composite score following treatment. The LCS improvement showed a significant correlation with the improvement in the VFQ-25 composite score, whereas the BCVA improvement was not correlated with the improvement in the VFQ-25 composite score. Stepwise multiple regression analyses revealed that, at the time of macular oedema resolution, the distance between the external limiting membrane and retinal pigment epithelium (ELM-RPE) and average ganglion cell-inner plexiform layer (GCIPL) thickness were associated with LCS.
CS had a stronger association with VR-QOL than with BCVA in patients with CRVO-CMO. With the resolution of macular oedema, CS was associated with ELM-RPE thickness and average GCIPL thickness.
Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this ...hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision.
Case study and clinicopathologic correlation.
A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age.
The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n = 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps).
Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps.
The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV.
Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy.
We conducted an in vivo study using Dutch pigmented rabbit eyes to test the usefulness of polyethylene glycol (PEG) sealant for the closure of sutureless sclerotomies in microincisional vitrectomy ...surgery (MIVS).
Three-port, 23-gauge vitrectomy was performed on rabbit eyes. After air leakage was confirmed by the application of 0.625% povidone-iodine at the sclerotomy site, PEG sealant was subconjunctivally injected using a 27-gauge needle through conjunctival incisions to cover the sclerotomy wounds, following which it was polymerized by the application of xenon light for 60 seconds. Ophthalmological examinations and intraocular pressure measurements were conducted the day before and 1, 3, 5, and 7 days after surgery. The eyes were enucleated for histological evaluation 7 days after surgery.
PEG sealant was rapidly polymerized by the application of xenon light after subconjunctival injection, and it firmly sealed the sclerotomies without air leakage, as confirmed by povidone-iodine dropping, in all cases. Conjunctival and scleral wounds closed with PEG sealant were successfully attached and remained intact till the end of the follow-up period. There was no sign of postoperative hypotony or infection in any eye, and no adverse effects of PEG sealant were found. In histological examination, linear scar formation and eosinophilic staining of collagen fibers were observed at the sclerotomy sites, while the sclerotomy tunnels appeared tightly closed.
PEG sealant can be useful for the closure of sutureless 23-gauge vitrectomy incisions in rabbits.
The PEG sealant may become an effective option for closing vitrectomy incisions including pediatric cases.
Mitochondria utilize diverse cytoskeleton-based mechanisms to control their functions and morphology. Here, we report a role for kinesin-like protein KLP6, a newly identified member of the kinesin ...family, in mitochondrial morphology and dynamics. An RNA interference screen using Caenorhabditis elegans led us to identify a C. elegans KLP-6 involved in maintaining mitochondrial morphology. We cloned a cDNA coding for a rat homolog of C. elegans KLP-6, which is an uncharacterized kinesin in vertebrates. A rat KLP6 mutant protein lacking the motor domain induced changes in mitochondrial morphology and significantly decreased mitochondrial motility in HeLa cells, but did not affect the morphology of other organelles. In addition, the KLP6 mutant inhibited transport of mitochondria during anterograde movement in differentiated neuro 2a cells. To date, two kinesins, KIF1Bα and kinesin heavy chain (KHC; also known as KIF5) have been shown to be involved in the distribution of mitochondria in neurons. Expression of the kinesin heavy chain/KIF5 mutant prevented mitochondria from entering into neurites, whereas both the KLP6 and KIF1Bα mutants decreased mitochondrial transport in axonal neurites. Furthermore, both KLP6 and KIF1Bα bind to KBP, a KIF1-binding protein required for axonal outgrowth and mitochondrial distribution. Thus, KLP6 is a newly identified kinesin family member that regulates mitochondrial morphology and transport.
To evaluate and compare paralesional and perilesional choriocapillaris vascular impairment in eyes with geographic atrophy with and without outer retinal tubulations (ORT).
Using swept-source optical ...coherence tomography angiography, 6 × 6 mm scans of eyes with geographic atrophy with and without ORT were acquired. Choriocapillaris en-face flow and structural images were binarized, before flow signal deficit (FD) analysis in the paraatrophy zone (a 500-µm-wide band adjacent to the geographic atrophy) and the periatrophy zone (a 500-µm-wide band adjacent to the latter).
Twenty-four eyes of 19 patients with ORT and 18 eyes of 15 patients without ORT were analyzed. With and without ORT, mean percental area of FD (%FD) was greater in para- than in periatrophy zone. The difference of %FD between para- and periatrophy zone (deltaFD) was lower in eyes with ORT (mean 1.8477%, 95% confidence interval 0.8607-2.8346) than without ORT (mean 4.0018%, 95% confidence interval 2.8622-5.1414).
In eyes with geographic atrophy caused by non-neovascular age-related macular degeneration, smaller reductions in FDs were found between the para- and periatrophy zone in eyes with ORT. In both cohorts, the paraatrophy zone had more FD than the periatrophy zone.
We compared postoperative metamorphopsia and optical coherence tomography (OCT) findings between eyes that underwent internal limiting membrane (ILM) peeling and the inverted flap (IF) technique for ...macular hole (MH).
This retrospective analysis included 64 eyes of 64 patients with idiopathic MH whose MH was closed after initial surgery. Thirty-nine patients were treated with pars plana vitrectomy (PPV) with ILM peeling, and 25 patients were treated with PPV with the IF technique. Best corrected visual acuity (BCVA), severity of metamorphopsia, and OCT images were collected before and 3, 6, and 12 months postoperatively. Based on the OCT images, the status of the external limiting membrane (ELM) and ellipsoid zone and the presence of hyperreflective plugs were assessed.
At baseline and 3, 6, and 12 months postoperatively, BCVA and severity of metamorphopsia were not significantly different between groups. The status of the ELM was significantly worse in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Significantly more hyperreflective plugs were observed in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Stepwise multiregression analysis revealed that hyperreflective plugs were significantly associated with the severity of metamorphopsia at 12 months postoperatively.
The alterations on the OCT were fewer in the ILM peeling group than in the IF group, while no significant differences were observed in postoperative severity of metamorphopsia between groups. Metamorphopsia was worse in eyes with hyperreflective plugs.
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