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To evaluate corneal endothelial cell loss after Baerveldt glaucoma implantation. We prospectively evaluated changes in endothelial cell density (ECD) in the cornea of 59 patients (59 eyes) who underwent Baerveldt glaucoma implantation. Tubes were inserted into the anterior chamber in 45 eyes and pars plana in 14 eyes. The primary outcome measure was the change in corneal ECD after Baerveldt glaucoma implantation. Secondary outcome measures included relationships between corneal ECD and optical coherence tomography images of tube parameters (tube-cornea distance and tube-cornea angle) and prognostic factors for corneal ECD loss. Corneal ECD decreased significantly by 9.2% at 12 months after surgery (P = 0.001). In the anterior chamber Baerveldt glaucoma implantation group, corneal ECD at the tube insertion quadrant decreased significantly by 9.6% at 3 months (P = <0.001), 10.7% at 6 months (P = <0.001), and 13.1% at 12 months (P = <0.001). Corneal ECD at the center decreased significantly at 6 months after surgery (7.2% loss; P = 0.012) and at 12 months after surgery (12.1% loss; P = 0.001). Corneal ECD at the contralateral quadrant decreased significantly at 12 months after surgery only (10.3% loss; P = 0.004). In the pars plana Baerveldt glaucoma implantation group, no significant loss of corneal ECD was found in any corneal areas at any post-surgery follow-up visits. Tube-cornea angle was negatively correlated with the rate of corneal ECD loss at the tube insertion quadrant; r = -0.55 (P = 0.0013). In multivariable analyses, exfoliation glaucoma and narrower tube-cornea angle were significant prognostic factors for severe corneal ECD loss (P = 0.0068 and P = 0.046, respectively). Anterior chamber Baerveldt glaucoma implantation causes corneal endothelial cell loss. Corneal endothelial cell loss starts at the tube insertion quadrant. Exfoliation glaucoma and narrower tube-corneal angle are associated with severe loss of corneal endothelial cells.

A large-scale proteomic approach was used to evaluate the protein profiles of aqueous humor obtained from patients with primary open angle glaucoma (POAG) and exfoliation glaucoma (EXG). The study population consisted of 15 POAG and 15 EXG patients, and 10 patients with no previous ophthalmic treatment as controls. Aqueous humor was collected at the beginning of surgery. Proteins were analyzed using the SOMAscan platform. Among the 7,335 human proteins identified in the aqueous humor of POAG and EXG patients, 215 and 330, respectively, were upregulated, as compared to controls. A pathway-enrichment analysis of the proteins upregulated in both POAG and EXG revealed enrichment of those involved in trabecular meshwork remodeling. Among the 43 and 23 proteins downregulated in POAG and EXG, respectively, was GSTP1, whose null genotype has been shown to increase the risk of POAG in Asians. SOMAscan analysis of the aqueous humor proteins of POAG and EXG patients revealed enrichment of pathways related to the onset and progression of glaucoma, as well as novel disease-associated proteins. These results demonstrate the advantages of SOMAscan, including its high detection sensitivity and accuracy even in analyses of a small number of samples.

The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23–25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

To identify the factors associated with the surgical outcomes of Baerveldt glaucoma implant (BGI) for open-angle glaucoma (OAG), the medical records of 51 consecutive OAG patients (age, 43–91 years) who underwent BGI were retrospectively reviewed (median follow-up, 21.7 months). Surgical success was defined as the following postoperative intraocular pressures (IOPs, mmHg): (A) 6 ≤ IOP ≤ 21; (B) 6 ≤ IOP ≤ 18; and (C) 6 ≤ IOP ≤ 15 without loss of light perception or additional glaucoma surgery. Univariate analysis showed that age (all criteria), glaucoma type (criterion C), and preoperative IOP (criteria A and B) were the candidate factors ( P  < 0.20). When the patients were divided into two groups according to median age (72 years), the success probability was higher in the older group for criteria B ( P  = 0.047) and C ( P  = 0.02), and the postoperative IOP was lower in the older group 1-year post-surgery ( P  = 0.002). Furthermore, the multivariate Cox proportional hazards model revealed that older age was independently associated with surgical success for criteria B (relative risk [RR], 0.94; P  = 0.02) and C (RR, 0.94; P  = 0.01). In conclusion, older age is a factor associated with the surgical success of BGI for OAG.

This study aimed to investigate the effects of substratum stiffness on the sensitivity of human conjunctival fibroblasts to transforming growth factor (TGF)-β, and to explore the molecular mechanism of action. Human conjunctival fibroblasts were cultured on collagen-coated plastic or silicone plates. The stiffness of the silicone plates was 0.2 or 64 kPa. Cells were treated by 2.5 ng/mL TGF-β2 with or without fibroblast growth factor (FGF)-2 (0-100 ng/mL) for 24 h or 48 h. The protein expression levels were determined by Western blot analysis. Cell proliferation was assessed using the WST-8 assay. FGF-2 suppressed the TGF-β-induced expression of α-smooth muscle actin (SMA) and collagen type I (Col I), but not fibronectin (FN). Both FGF-2 and TGF-β2 increased cell proliferation without an additive effect. The induction of α-SMA by TGF-β2 was decreased on the soft substratum, without any change in the expression level or subcellular location of Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). FGF-2 suppressed TGF-β-induced α-SMA expression even on the soft substratum. FGF-2 treatment and a soft substratum suppressed TGF-β-induced transdifferentiation of conjunctival fibroblasts into myofibroblasts. FGF-2 attenuated the TGF-β-induced expression of α-SMA, even on a soft substratum.

We evaluated bleb fluid images taken after Baerveldt glaucoma implantation. T2-weighted images of bleb fluid were scanned with 3 Tesla magnetic resonance imaging in 52 patients who had undergone tube-shunt surgery using the 350-mm 2 endplate Baerveldt glaucoma implant; three-dimensional images were constructed from these images. Bleb fluid images were classified into either a layer of bleb fluid on either side of the endplate (double bleb layer group; n = 24) or one layer outside the endplate (single bleb layer group; n = 28). Despite there being no correlation between the bleb volume and the postoperative IOP ( r  = −0.080; P  = 0.57), the double bleb layer group had significantly lower postoperative IOPs than the single bleb layer group (12.3 ± 3.8 mmHg vs. 14.7 ± 4.1 mmHg, respectively; P  = 0.033). The single bleb layer was significantly related to higher numbers of prior intraocular surgeries (relative risk = 2.85; P  = 0.0014). Formation of a layer of bleb fluid on either side of the endplate may have resulted in the lower postoperative IOPs after Baerveldt glaucoma implantation. Repeated intraocular surgery adversely affects formation of the double bleb layer.

Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K −tg mice in vivo . While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro , it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro . These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.

[This corrects the article DOI: 10.1371/journal.pone.0242626.].

We compared early postoperative complications between trabeculectomy and Ex-PRESS implantation. Enrolled patients with 39 primary open-angle or 25 exfoliative glaucoma were randomly assigned to receive trabeculectomy (trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS group). Primary outcomes were early postoperative complications, including postoperative anterior chamber inflammation, frequencies of hyphema, flat anterior chamber, choroidal detachment, hypotonic maculopathy, and the change of visual acuity. The postoperative flare values in trabeculectomy group were higher than those in the Ex-PRESS group (overall, P  = 0.004; and 10 days, P  = 0.02). Hyphema occurred significantly more frequently in the trabeculectomy group ( P  = 0.0025). There were no significant differences of the other primary outcomes between the two groups. Additionally, duration of anterior chamber opening was significantly shorter in the Ex-PRESS group ( P  = 0.0002) and the eyes that had iris contact with Ex-PRESS tube had significantly shallower anterior chambers than did the eyes without the iris contact ( P  = 0.013). The Ex-PRESS implantation prevented early postoperative inflammation and hyphema in the anterior chamber and shortened the duration of anterior chamber opening. Iris contact with the Ex-PRESS tube occurred more frequently in eyes with open-angle glaucoma and shallow anterior chambers.

Background To compare the lamina cribrosa between eyes with and without neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical coherence tomography. Methods Forty-six patients with proliferative diabetic retinopathy were enrolled in this cross-sectional study. The patients were divided into two groups based on the absence or presence of NVG (the non-NVG group and the NVG group, respectively). The intraocular pressure (IOP), circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina cribrosa depth (ALD), and laminar thickness (LT) were compared between the groups. Results In the non-NVG group, the mean age was 66.2 ± 2.4 (mean ± standard error) years, mean maximum IOP was 18.8 ± 1.8 mmHg, mean cpRNFL thickness was 91.2 ± 3.9 μm, mean ALD was 407.0 ± 22.9 μm, and mean LT was 155.0 ± 4.7 μm. In the NVG group, the mean age was 61.4 ± 2.1 years, mean maximum IOP was 33.1 ± 1.6 mmHg, mean cpRNFL thickness was 73.6 ± 3.4 μm, mean ALD was 403.9 ± 20.1 μm, and mean LT was 156.9 ± 4.2 μm. The IOP was significantly higher and the cpRNFL was significantly thinner in the NVG group ( P  < 0.001 and P  = 0.002, respectively). However, the age, ALD, and LT were not statistically different between the groups ( P =  0.151, 0.919, and 0.757, respectively). Conclusions Although the cpRNFL was thinner, the structure of the lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal ganglion cells in NVG patients was prior to lamina cribrosa deformation.