BackgroundThere is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).Methods and FindingsEighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.ConclusionsProteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
Purpose A subretinal implant termed CPCB-RPE1 is currently being developed to surgically replace dystrophic RPE in patients with dry age-related macular degeneration (AMD) and severe vision loss. CPCB-RPE1 is composed of a terminally differentiated, polarized human embryonic stem cell-derived RPE (hESC-RPE) monolayer pre-grown on a biocompatible, mesh-supported submicron parylene C membrane. The objective of the present delivery study was to assess the feasibility and 1-month safety of CPCB-RPE1 implantation in Yucatán minipigs, whose eyes are similar to human eyes in size and gross retinal anatomy. Methods This was a prospective, partially blinded, randomized study in 14 normal-sighted female Yucatán minipigs (aged 2 months, weighing 24-35 kg). Surgeons were blinded to the randomization codes and postoperative and post-mortem assessments were performed in a blinded manner. Eleven minipigs received CPCB-RPE1 while three control minipigs underwent sham surgery that generated subretinal blebs. All animals except two sham controls received combined local (Ozurdex™ dexamethasone intravitreal implant) and systemic (tacrolimus) immunosuppression or local immunosuppression alone. Correct placement of the CPCB-RPE1 implant was assessed by in vivo optical coherence tomography and postmortem histology. hESC-RPE cells were identified using immunohistochemistry staining for TRA-1-85 (a human marker) and RPE65 (an RPE marker). As the study results of primary interest were nonnumerical no statistical analysis or tests were conducted. Results CPCB-RPE1 implants were reliably placed, without implant breakage, in the subretinal space of the minipig eye using surgical techniques similar to those that would be used in humans. Histologically, hESC-RPE cells were found to survive as an intact monolayer for 1 month based on immunohistochemistry staining for TRA-1-85 and RPE65. Conclusions Although inconclusive regarding the necessity or benefit of systemic or local immunosuppression, our study demonstrates the feasibility and safety of CPCB-RPE1 subretinal implantation in a comparable animal model and provides an encouraging starting point for human studies.
ABSTRACT.Purpose: To compare cytokines in undiluted vitreous of treatment-naı¨ve patients with macular oedema without vitreomacular traction secondary to branch (BRVO), central (CRVO) and hemi-central (H-CRVO) retinal vein occlusion. Methods: Ninety-four patients (median age 72 years, 42 men) underwent an intravitreal combination therapy, including a single-site 23-gauge core vitrectomy and the application of bevacizumab and dexamethasone due to vision-decreasing macular oedema. Among these were 43 patients with BRVO, 35 with CRVO and 16 patients with hemi-CRVO, which were distributed in a fresh or old retinal vein occlusion type (seven or more months after onset). Undiluted vitreous samples were analysed for interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF-A) with cytometric BEAD assay. Vitreous samples from patients with idiopathic epiretinal membrane served as controls (n = 14). Results: The mean cytokine values were highest in the CRVO group with IL-6 = 64.7 pg ⁄ ml (SD ± 115.8), MCP-1 = 1015.8 pg ⁄ ml (±970.1) and VEGF-A = 278.4 pg ⁄ ml (±512.8), followed by the H-CRVO group with IL-6 = 59.9 pg ⁄ ml (SD ± 97.5), MCP-1 = 938.8 pg ⁄ ml (±561.1) and VEGF-A = 211.5 pg ⁄ ml (±232.4). The BRVO group had IL-6 = 23.2 pg ⁄ ml (SD ± 48.8), MCP-1 = 602.6 pg ⁄ ml (±490.3) and VEGF-A = 161.8 pg ⁄ ml (±314.4). The values of MCP-1 and VEGF-A were significantly different for CRVO or H-CRVO versus BRVO. All values were significantly higher than in the control samples, which had 6.2 ± 3.4 pg ⁄ ml (IL-6), 253 ± 74 pg ⁄ ml (MCP-1) and 7 ± 4.9 pg ⁄ ml (VEGF-A). Within the old RVO type, only MCP-1 was significantly different for CRVO or H-CRVO versus BRVO. Conclusions: Both inflammatory markers and VEGF-A were higher in CRVO and H-CRVO than in BRVO undiluted vitreous samples. It seems that monocyte recruitment to the vessel wall, which might underlie the importance of eosinophils in tissue remodelling after RVO, is of special interest owing to the significant difference in MCP-1 in the older RVO types.Key words: cytometric bead array -interleukin 6 -monocyte chemoattractant protein -retinal vein occlusion -vascular endothelial growth factor -vitreous samples Acta Ophthalmol. 2012: 90: e98-e103
Purpose. We hypothesized that reaction times (RTs) for a switch release are faster for hand-controlled than for foot-controlled switches for physiological and anatomical reasons (e.g., nerve conduction speed). The risk of accidental trauma could be reduced if the surgeon reacted quicker and therefore improve the surgical outcome. Method. We included 47 medical professionals at USC. Demographics and handedness were recorded. Under a microscope, a simple reaction time test was performed, testing all extremities multiple times in a random order. Additionally, a subjective questionnaire was administered. Results. The mean RTs for hands are 318.24 ms ± 51.13 and feet 328.69 ± 48.70. The comparison of hand versus foot showed significant shorter RTs for the hand (P = 0.025). Partially significant differences between and within the experience level groups could be demonstrated by level of education (LE) and microscopic surgeries/week (MSW) (P = 0.57–0.02). In the subjective questionnaire, 91.5% (n = 43/47) of test subjects prefer to use hand controls. Conclusion. Our data show that the RT for hands is faster than feet. Similarly the subjective questionnaire showed a greater preference for hand actuation. This data suggest a hand-controlled ophthalmic instrument might have distinct advantages; however, clinical correlation is required.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.