Characterization of peroxidase and catalase genes in defense mechanisms of Physcomitrella patens

Systemic acquired resistance (SAR) and the hypersensitive response (HR) are two important induced defense mechanisms in plants. SAR is the development of an enhanced resistance to a pathogen due to a prior encounter. It results in faster and more effective defensive action within the plant upon a second-time pathogen attack. HR is a plant defense mechanism that utilizes reactive oxygen species (ROS) to attack pathogens at the site of an infection. ROS can be generated in many ways; however, it is specifically known that plants use the enzyme peroxidase to generate the ROS hydrogen peroxide during HR. Plants also use the enzyme catalase to generate water from hydrogen peroxide in order to contain and control the toxicity. Much is known about SAR and HR in economically important vascular plants such as rice and corn; however, they have only recently been identified in nonvascular plants such as moss. This study aims to identify and characterize the roles of peroxidase and catalase in HR and SAR in the model moss species Physcomitrella patens; specifically, how the expression of peroxidase and catalase genes in this species is affected by exposure to the fungal elicitor β-glucan. This will provide insight into the SAR and HR of moss and other nonvascular plants and into the evolution of plant defense mechanisms

User Research and Real User Problems: Improving the User Experience of Online Shopping

“User Research and Real User Problems: Improving the User Experience of Online Shopping” is a creative thesis project that incorporates user research, user experience design, and coding skills. The first phase of the project consisted of market research and generative user research to develop a plan for a shopping companion app. The findings of this research shaped the scope of the project according to user needs and established the basis of a plan to create a progressive web application and Google Chrome browser extension that will respond to specific user problems. These tools would solve three key user problems: users do not know what size to order when shopping online, users are uncertain about the items they order online due to a lack of familiarity with the items prior to purchase, and users cannot visualize items on themselves when shopping online. I constructed a user experience that would solve these problems, incorporating the principles of user-centered design and user experience best practices. The progressive web application and Google Chrome extension will work together to store user-provided data, create size/style recommendations based on this data, and display crowd-sourced reviews for items in online stores. Using the Vue.js JavaScript framework, Firebase data storage, and the Agile Project Management Methodology, I built a proof of concept for the progressive web app, and have outlined a comprehensive plan for next steps

Ranibizumab For Diabetic Macular Edema Refractory To Multiple Prior Treatments

Purpose: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. Methods: Retrospective chart review. Results: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 μm. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 μm. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. Conclusion: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab

Efficacy of Dexamethasone Intravitreal Implant For Refractory Macular Edema Caused by Retinal Vein Occlusion

Purpose: To investigate efficacy of dexamethasone intravitreal (DEX) implant in treating refractory macular edema caused by retinal vein occlusion. Methods: Retrospective chart review. Results: Twenty-two eyes with refractory macular edema caused by retinal vein occlusion were treated with a mean of 2.2 DEX over 12 months. Patient had previously received a mean of 7 treatments (laser, bevacizumab, and/or triamcinolone) for macular edema present for at least 4 months duration (mean 20.8 ± 17.6 months, range 4–72 months) before starting DEX. Mean baseline visual acuity was 20/91, and mean central subfield thickness was 506 μm. DEX improved mean best-corrected visual acuity to 20/75 and 20/66 at 7 weeks and 6 months follow-up, although it worsened to 20/132 at 12 months. Mean central subfield thickness improved to 292, 352, and 356 μm at 7 weeks, 6 months, and 12 months follow-up, respectively. There was a statistically significant association between number of DEX treatments and central subfield thickness (P = 3.28 × 10−9). There was a statistically significant association between number of days followed and best-corrected visual acuity (P = 0.006). Six of 12 (50%) phakic patients developed visually significant cataract requiring surgery. Five of 22 (23%) patients developed ocular hypertension (intraocular pressure > 30) and consequently did not undergo further treatment with DEX. Conclusion: DEX resulted in sustained anatomical reduction of retinal vein occlusion–associated refractory macular edema, although this did not translate into long-term best-corrected visual acuity improvement in either phakic or pseudophakic patients, possibly related to chronic structural alterations in the retina despite reduction of edema

Angiopoietins as Targets for Diabetic Retinopathy Treatment

Diabetic eye diseases, such as diabetic retinopathy (DR) and diabetic macular edema (DME) are among the leading causes of blindness in developed countries. Anti-VEGF therapies such as, ranibizumab, aflibercept and off-label bevacizumab have become first-line treatment for DME. While randomized controlled trials show significant improvement in vision, these anti-VEGF agents have limited durability leading to a significant treatment burden, as reflected in real-world studies, which generally demonstrate under-treatment and less favorable visual acuity outcomes than observed in prospective trials. Alternative pathways, such as the Tie-2 angiopoietin pathway may address unmet needs, with potential for greater efficacy or durability when compared to anti-VEGF monotherapy. While some Tie-2 angiopoietin therapeutic agents, such as nesvacumab, ARP-1536 or AKB-9778, did not meet primary endpoints in clinical trials, other agents have shown promise. One such agent is faricimab, a bispecific antibody inhibiting both VEGF-A and Ang-2. The phase 3 DME trials (YOSEMITE and RHINE) demonstrated favorable safety, visual, and durability outcomes; patients receiving faricimab injection every 4 months achieved similar visual gains as those receiving aflibercept injection every 2 months. Another agent, AXT107 is a peptide that inhibits VEGFR2 and modifies Ang-2 to behave more similarly to Ang-1, promoting vascular stability. This drug is currently undergoing phase 1/2a trials for safety and bioactivity to be completed in May 2022

The Effect of Video Quality on Deep Learning Nystagmus Detection

Nystagmus identification and interpretation is a challenging endeavor for non-expert neuro-otologist and neuro- ophthalmologist. In video-based eye tracking, nystagmus detection traditionally relies on the ability to track pupil and generate appropriate waveforms. It has been shown that video frame rates less than 30Hz may limiting eye tracking nystagmus detection

Vascular Endothelial Growth Factor Antagonists: Promising Players in the Treatment of Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab monotherapy in a phase 1/2a trial. Sustained-release anti-VEGF therapies include the ranibizumab Port Delivery System (in phase 3 studies), GB-102 (Phase 2b), OTX-TKI (phase 1), and Durasert (preclinical). Suprachoroidal delivery of the tyrosine kinase inhibitor, axitinib, is in preclinical studies. Genetic therapies in phase 1 studies include RGX-314 and ADVM-022, which introduce a viral vector that modifies the retina’s cellular apparatus to create an anti-VEGF biofactory, potentially serving as a one-time treatment. Further investigation is warranted for drugs and delivery systems that hope to advance visual outcomes and reduce treatment burden of nAMD