Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain-Brief Report.

OBJECTIVE: THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the core of the ischemic tissue Thbd expression was decreased compared with the contralateral side. We generated a novel Cre/loxP-based mouse line that allows for the inducible deletion of Thbd specifically in brain endothelial cells, which worsened stroke outcome 48 hours after middle cerebral artery occlusion. Unexpectedly, we found no signs of increased coagulation, thrombosis, or inflammation in the brain but decreased vessel diameters and impaired angiogenesis in the peri-infarct area that led to a reduced overall vessel length 1 week after stroke induction. CONCLUSIONS: Endogenous THBD acts as a protective factor in the brain during ischemic stroke and enhances vessel diameter and proliferation. These previously unknown properties of THBD could offer new opportunities to affect vessel function after ischemia and thereby improve stroke outcome.

Targeting the interaction of pleiotrophin and VEGFA165 with protein tyrosine phosphatase receptor zeta 1 inhibits endothelial cell activation and angiogenesis.

Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is a transmembrane tyrosine phosphatase (TP) that serves as a receptor for pleiotrophin (PTN) and vascular endothelial growth factor A 165 (VEGFA165) to regulate endothelial cell migration. In the present work, we identify a PTN peptide fragment (PTN97-110) that inhibits the interaction of PTN and VEGFA165 with PTPRZ1 but not VEGF receptor 2. This peptide abolishes the stimulatory effect of PTN and VEGFA165 on endothelial cell migration, tube formation on Matrigel, and Akt activation in vitro. It also partially inhibits VEGFA165-induced VEGF receptor 2 activation but does not affect ERK1/2 activation and cell proliferation. In vivo, PTN97-110 inhibits or dysregulates angiogenesis in the chick embryo chorioallantoic membrane and the zebrafish assays, respectively. In glioblastoma cells in vitro, PTN97-110 abolishes the stimulatory effect of VEGFA165 on cell migration and inhibits their anchorage-independent growth, suggesting that this peptide might also be exploited in glioblastoma therapy. Finally, in silico and experimental evidence indicates that PTN and VEGFA165 bind to the extracellular fibronectin type-III (FNIII) domain to stimulate cell migration. Collectively, our data highlight novel aspects of the interaction of PTN and VEGFA165 with PTPRZ1, strengthen the notion that PTPRZ1 is required for VEGFA165-induced signaling, and identify a peptide that targets this interaction and can be exploited for the design of novel anti-angiogenic and anti-glioblastoma therapeutic approaches.

Scleral fixation of Carlevale intraocular lens: A new tool in correcting aphakia with no capsular support.

PURPOSE: To report the clinical outcomes of the use of a novel specially designed scleral fixated intraocular lens, the Carlevale intraocular lens (carlevale IOL, Soleko, Italy) for the correction of aphakia in the absence of capsular support of variable etiology. METHODS: This retrospective, non-comparative study included 169 eyes of 169 consecutive patients who underwent 3-port pars plana vitrectomy and scleral fixation on Carlevale IOL. Inclusion criteria were at least 6 months' follow-up period, patients > 18 years old who underwent vitrectomy and Carlevale IOL placement for aphakia and inadequate capsular support. RESULTS: The median follow up period of 9 months (range 6-18 months). Mean post-operative BCVA at the last follow-up visit was 20/25 (0.09 ± 0.1 LogMAR), improving from a mean baseline BCVA of 20/80 (0.58 ± 0.49 LogMAR), a statistically significant change (p = 0.0001). Regarding the post-operative complications, a transient rise in the IOP was observed in 28 patients (16.5%) and mild vitreous hemorrhage was observed in the immediate post-operative period in eight eyes (4.7%) and it spontaneously resolved within 3 weeks. All patients demonstrated good IOL position at the end of the follow-up without IOL capture. None of the patients required re-operation. CONLCUSION: The present study represents the largest to date in evaluating the use of carlevale IOL in patients with aphakia and inadequate capsular support. The technique is safe and provides excellent post-operative IOL fixation without IOL capture in any of the patients studied.

Scleral Fixation of Carlevale Intraocular Lens in Children: A Novel Tool in Correcting Aphakia With No Capsular Support.

BACKGROUND AND OBJECTIVE: To report the clinical outcomes of the use of a novel, specially designed, scleral-fixated intraocular lens (IOL) for the correction of aphakia in the absence of capsular support of variable etiology in children. PATIENTS AND METHODS: This is a retrospective, noncomparative, interventional case series of five eyes of five consecutive patients who underwent three-port pars plana vitrectomy and scleral fixation of the IOL. Inclusion criteria were at least 6 months of follow-up in children who underwent vitrectomy and IOL placement for aphakia and inadequate capsular support. Patients were excluded from the analysis if there was a previous open globe injury or any other ocular comorbidity such as macular pathology or previous surgery for retinal detachment, glaucoma, corneal transplantation, or strabismus. RESULTS: The median follow-up period was 9 months (range: 7-13 months). The median age was 8 years (range: 2-10 years), and the male-to-female ratio was 5 to 0. Mean postoperative best-corrected visual acuity (VA) at the last follow-up visit was 20/32 (0.26 ± 0.32 logMAR [mean ± standard deviation]), improving from a mean baseline uncorrected VA of 20/800 (1.6 ± 0.7 logMAR), a statistically significant change (P = .003). The uncorrected postoperative VA was 20/63 (0.54 ± 0.37 logMAR). No significant postoperative complications were noted and all patients had good IOL position at the end of the follow-up without IOL capture. The mean tilt in four eyes (the 2-year-old was excluded from the analysis) was 2.1 ± 1.9 degrees. None of the patients required reoperation. CONLCUSIONS: The present study represents the first to date in evaluating the use of a scleral-fixated IOL in patients with aphakia and in pediatric patients with inadequate capsular support. The technique is safe and provides excellent postoperative IOL fixation without IOL capture in any of the patients studied. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:94-101.].

Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations.

Intraocular pressure (IOP) rise after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD) can be either short-term or long-term and may require medical intervention. Short-term IOP spikes are a fairly common and well recognized complication of anti-VEGF injections. Long-term IOP rise is less well-understood and disputed as a complication by some authors. We try to review current literature on the subject and especially studies focused on the prevalence of this complication, speculate on possible mechanisms of IOP rise and discuss correlations of long-term IOP rise with the nature of the injected agent, average number of injections, previous glaucoma history and other factors. How to cite this article: Kampougeris G, Spyropoulos D, Mitropoulou A. Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations. J Current Glau Prac 2013;7(1):19-24.

Peripapillary retinal nerve fibre layer thickness measurement with SD-OCT in normal and glaucomatous eyes: distribution and correlation with age.

AIM: To determine peripapillary retinal fiber layer thickness (RNFL) measured with spectral domain optical coherence tomography (SD-OCT) in normal and glaucomatous eyes in a large sample of exclusively white population and compare results with other similarly constructed studies. METHODS: Average, maximum, minimum and per quadrant RNFL thickness were measured in normal and glaucomatous Greek patients with a scanning laser ophthalmoscope (SLO)/SD-OCT device. The effect of age in normal RNFL thickness was also determined. RESULTS: A total of 278 normal (278 patients) and 67 glaucomatous (67 patients) eyes were included in the study. Average RNFL thickness was 114.8±13.3µm in normal and 92.1±18.5µm in glaucomatous eyes (P<0.001). In normal discs, superior quadrant was the thickest, followed by the inferior, nasal and temporal. Decline of normal RNFL thickness with age was statistically significant for average RNFL thickness (1.92µm per decade of life) and for the superior and inferior quadrants of the disc. CONCLUSION: SD-OCT peripapillary RNFL measurements can be used to distinguish between normal and glaucomatous eyes and establish normative databases, since normal disc measurements differ between different ethnic groups and between different SD-OCT devices.