Treatment Of AMD Research Articles

Competitive adsorption behavior and adsorption mechanism of limestone and activated carbon in polymetallic acid mine water treatment

Acid mine water (AMD) can cause significant environmental hazards due to its high concentration of metal ions, so the development of effective treatment methods is essential to mitigate its impact. In this study, adsorption experiments were conducted using limestone (LS) and activated carbon (AC) to explore the adsorption efficiency for different concentrations of metal ions. Adsorption was evaluated by static and competitive batch tests. The adsorbent mechanism was investigated using analytical techniques such as SEM, FTIR and XRD. The efficacy of LS and AC for competitive adsorption of Fe, Mn, Zn and Cu ions from AMD was evaluated. The study analyzed the effect of environmental conditions such as initial concentration and ionic strength on the adsorption efficiency. The results showed that LS showed high adsorption capacity for Fe and Cu, but was less effective in competitive adsorption of Mn. AC showed superior adsorption performance for Fe and Cu under competitive conditions due to its high surface area and functional groups. Both adsorbents showed selective efficacy influenced by the physicochemical properties of metal ions. This study helps to guide the optimization of adsorbents in AMD treatment and highlights the importance of selecting suitable materials based on specific metal ion properties.

Acidophilic sulphate-reducing bacteria: Diversity, ecophysiology, and applications.

Acidophilic sulphate-reducing bacteria (aSRB) are widespread anaerobic microorganisms that perform dissimilatory sulphate reduction and have key adaptations to tolerate acidic environments (pH <5.0), such as proton impermeability and Donnan potential. This diverse prokaryotic group is of interest from physiological, ecological, and applicational viewpoints. In this review, we summarize the interactions between aSRB and other microbial guilds, such as syntrophy, and their roles in the biogeochemical cycling of sulphur, iron, carbon, and other elements. We discuss the biotechnological applications of aSRB in treating acid mine drainage (AMD, pH <3), focusing on their ability to produce biogenic sulphide and precipitate metals, particularly in the context of utilizing microbial consortia instead of pure isolates. Metal sulphide nanoparticles recovered after AMD treatment have multiple potential technological uses, including in electronics and biomedicine, contributing to a cost-effective circular economy. The products of aSRB metabolisms, such as biominerals and isotopes, could also serve as biosignatures to understand ancient and extant microbial life in the universe. Overall, aSRB are active components of the sulphur and carbon cycles under acidic conditions, with potential natural and technological implications for the world around us.

Use of artificial intelligence for recognition of biomarkers in intermediate age-related macular degeneration

Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research. In this context AI provides a solution by fully automatic segmentation and therefore delivers exact, reproducible and quantitative analyses of AMD-related biomarkers. Furthermore, the application of AI in iAMD facilitates the risk assessment and the development of structural endpoints for new forms of treatment. For example, the quantitative analysis of drusen volume and hyperreflective foci with AI algorithms has shown a correlation with the progression of the disease. These technological advances therefore improve not only the diagnostic precision but also support future targeted treatment strategies and contribute to the prioritized target of personalized medicine in the diagnostics and treatment of AMD.

THE ANALYSIS STUDY OF VISUAL IMPAIRMENT AND BLINDNESS DUE TO MACULAR DISEASES: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: DME and AMD are major causes of blindness, affecting the macula and central vision. AMD accounts for 8.7 of global blindness cases. Understanding AMD beyond the retina can provide insights into its pathophysiology, consequences, therapy, and clinical course. Anti-VEGF agents have shown promise in treating AMD, but a definitive treatment remains unidentified. Methods: Following PRISMA 2020 guidelines, this systematic review concentrated on full-text English literature published between 2014 and 2024. Editorials and review articles that appeared in the same journal as the submission were not accepted without a DOI. A number of websites, including ScienceDirect, PubMed, and SagePub, were utilized to gather the literature. Result: The study looked at more than 400 publications using reputable sources including Science Direct, SagePub, and PubMed. After it was decided that eight publications needed greater investigation, a more extensive review of the entire literature was carried out. Conclusion: BCVA is crucial in the treatment of AMD and DME, with targeting VEGF being an effective approach. However, their effectiveness in other forms of AMD is less convincing. Chronic inflammation is a key factor in retinal diseases, including AMD. DME treatment requires a multidisciplinary approach, with anti-VEGF agents being the first-line treatment.

The Impact of Blood and Urine Biomarkers on Age-Related Macular Degeneration: Insights from Mendelian Randomization and Cross-sectional Study from NHANES

IntroductionAge-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves a variety of risk factors, including lipid metabolism and inflammation. This study aims to elucidate the causal relationships between biomarkers related to these processes and AMD, leveraging Mendelian randomization (MR) and cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES).MethodWe conducted a two-phase study, initially using MR to explore the causality between 35 biomarkers and various AMD subtypes, followed by observational analysis with NHANES data to validate these findings.ResultsMR analysis identified a protective role of TG and a risk factor role of HDL-C and CRP in AMD development. NHANES data corroborated these findings, highlighting a nuanced relationship between these biomarkers and AMD. Notably, lipid metabolism-related biomarkers showed stronger associations with early AMD, whereas CRP’s significance was pronounced in late AMD.ConclusionThis comprehensive analysis, combining MR with NHANES data, reinforces the importance of lipid metabolism and inflammation in AMD’s etiology. Future research should further investigate these biomarkers’ mechanisms and their potential as therapeutic targets for AMD prevention and treatment.

Intracellular Trafficking Pathway and ROS Scavenging Activity of Glycol Chitosan‐Coated Cerium Oxide Nanoparticles in a Pathological AMD‐Like Model

AbstractAge‐related macular degeneration (AMD) is a degenerative eye disease that primarily affects the macula. AMD is a leading cause of vision loss in individuals over the age of 65, particularly more common in Caucasians than in other racial groups. Cerium oxide nanoparticles (CNPs) have emerged as highly promising nanomaterials in the treatment of AMD due to their potent antioxidant properties. In pathological damages of AMD conditions, characterized by oxidative stress resulting from an overproduction of reactive oxygen species (ROS), CNPs possess significant promise for attenuating the pathogenic processes and advancing therapeutic interventions. Despite their potential clinical applications, the widespread use of CNPs is greatly hampered by limited water solubility, and concerns have arisen about their potential impact on normal ROS production in mitochondria. Here, the antioxidative activity of glycol chitosan‐coated CNPs (namely, GCCNPs) and their behavior in mouse primary RPE (mRPE) cells are reported through an in vitro trafficking study. This findings demonstrate that GCCNPs effectively neutralize excessive ROS and prefer to exclusively accumulate in cytosol without any uptake in the nucleus and mitochondria of the mRPE cells. Moreover, GCCNPs demonstrated therapeutic effects by reducing the ROS level in a laser‐induced choroidal neovascularization (CNV) AMD‐like murine model.

Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration

BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death.MethodsA combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question.ResultsUA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy.ConclusionsCollectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.Graphical

Timely care for age-related macular degeneration: a qualitative study among retina specialists in Israel

BackgroundAge-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients.MethodsQualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted.ResultsBased on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population.ConclusionsLoss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups.Highlights• Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas.• Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted.• The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population• Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment.• Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups.

Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2μg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration.

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.

Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry

PurposeWe used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the two pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the two monthly treatment arms from the clinical trial. DesignRetrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data SubjectsAll treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for one year from either the CATT or the IRIS Registry MethodsPatients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all non-imaging based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity. ResultsWe identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n= 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n=261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (Exact Matching: 1.9 letters +/- 14.0 vs. IPSW: 2.8 letters +/- 15.0 letters, p=0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (Exact Matching: 2.4 letters +/- 15.4 vs. IPSW: 2.1 letters +/- 16.0 letters, p=0.79). ConclusionsBoth exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared to the clinical trial.

Systemic Arterial Hypertension and Ophthalmohypertension as Independent Risk Factors for Poor Response to Antiangiogenic Therapy with Line 1 Drugs in Neovascular Age-related Macular Degeneration

Purpose: to assess hypertension as a risk factor for a poor response to antiangiogenic therapy.Patients and methods. Systemic blood pressure was studied in 84 patients (92 eyes) with age-related macular degeneration who were treated with intravitreal injections of Eilea in a fixed mode.Results. It was found that significantly more often a poor response to treatment in the form of partial non-resposing or progression of the disease, despite treatment, is associated with elevated diastolic blood pressure (DBP, p = 0.01). An increase in systolic (SBP) blood pressure in patients with arterial hypertension and AMD is accompanied by an increase in eye perfusion pressure (p &lt; 0.01), which apparently worsens the absorption of angiostatics and causes a poor response to treatment. According to the results of the study, the most favorable corridor of SBP values associated with ideal response is in the range of values of 104–140 mm Hg, and DBP is in the range of 68–80 mm Hg st., which should be taken as the recommended parameters of blood pressure in patients with nVMD receiving a course of treatment for Eylea. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to treatment with nVMD with line 1 anti-VEGF therapy drugs. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to nVMD treatment with line 1 anti-VEGF therapy drugs. The biomarker associated with the ideal response was — 12.6 mm Hg, and the corridor of recommended values — 11–21 mm Hg. An increase in ophthalmotonus with the output of personalized values beyond this corridor seems to worsen the outcome of treatment.Conclusion. The identification of modifiable risk factors is extremely important in practical ophthalmology, as it opens up the possibility of increasing the patient’s chances of a better treatment outcome. Modifiable risk factors are valuable and powerful tools that replenish our arsenal. Information about them is important not only in the treatment of AMD, but can also be the patient’s motivation for switching to a healthy lifestyle and reducing the risk of developing the disease.

Risk Factor of Neovascular Age­related Macular Degeneration Progression after Cataract Surgery

The prevalence of late AMD, including neovascular AMD or geographic atrophy, and cataract in the same eye after age 80 years is estimated to be 12 and 68 %, respectively. There is currently no consensus on whether cataract surgery is beneficial or harmful for people with dry AMD. Although cataract surgery has been reported to provide better visual outcomes in eyes with AMD 6 months after surgery compared with previously followed eyes, it is unclear whether the timing of surgery relative to the start of AMD treatment influences long-term outcomes. The question of risk factors predisposing to the occurrence of exudation after cataract surgery in people with nAMD remains controversial.

The impact of COVID-19 on aflibercept treatment of neovascular AMD in Sweden – data from the Swedish Macula Register

BackgroundThe purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up.MethodsThis is a retrospective observational study including 2915 treatment naïve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year ± 2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher’s exact test were used to compare outcomes between the groups.ResultsBaseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2 ± 14.1 letters to 64.8 ± 16.1 letters (n = 921); p < 0.0001. In the pandemic group, VA increased from 61.1 ± 15.8 to 64.9 ± 16.9 (n = 575); p < 0.0001. There was no significant difference in mean VA change between the groups; p = 0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p < 0.0001.ConclusionsThe pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic.

Anti‐VEGF for wet AMD ‐ Which drug and how often?

Introduction of anti‐VEGF agents as a treatment option of neovascular AMD (ex AMD) in 2004 have brought dramatic progression in the treatment of that disease and until now it is a gold standard for ex AMD management. In that course we will present following subjects concerning ex AMD treatment with the use of anti‐VEGF drugs. We will present a variety of anti‐VEGF agents used now for ex AMD treatment: ranibizumab, aflibercept, brolucizumab, faricimab. We will discuss the differences between these drugs, in terms of efficacy and safety. Results from clinical trials and real life observations will be presented. Novel drug‐faricimab will be presented as bispecific antibody‐which inhibits both angiopoietin‐2 and VEGF‐A which possesses superior therapeutic action in reducing vascular leaking and inflammatory responses. The rules of different regiments of anti‐VEGF treatment will be discussed‐ fixed, PRN (pro re nata), TREX (treat and extend). We will discuss as well two important problems: When to switch to the other drug in ex AMD treatment and which were the results of the treatment of patients with ex AMD during the COVID‐19 pandemic. New therapeutic strategies in ex AMD will be presented as research in under way to develop novel anti‐VEGF agents with longer duration of action and to identify new methods of delivery with long‐ term release of anti‐VEGF medication as intraocular implants.

Real-life neovascular AMD treatment considering reimbursement in Turkiye: One-year comparison of switching to intravitreal ranibizumab or aflibercept after treatment failure with three loading intravitreal bevacizumab injections.

To compare one-year anatomical and functional results of switching to an on-label intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent (intravitreal ranibizumab [IVR] or aflibercept [IVA]) after treatment failure with three loading doses of off-label intravitreal bevacizumab (IVB), which is mandatory in the treatment of neovascular age-related macular degeneration (nAMD) to get reimbursement from Social Security Institution in Turkiye. This comparative, real-life, retrospective cohort study included treatment-naïve nAMD patients treated starting with three loading doses of IVB, switched to three loading doses of IVR and IVA due to treatment failure after IVB loading, and followed up one year with a treat-and-extend (T&E) protocol with 2-week extension/shortening intervals. The primary outcomes were changes in best-corrected visual acuity (BCVA; logMAR) and central macular thickness (CMT, µm) one year after the switch, and the secondary outcomes were maximum treatment intervals, number of injections, and disease activity rates. The mean age (72.9±8.2 and 72.2±6.7, p=0.677) and gender (60.0% and 47.4% females, p=0.398) were similar among the IVR (35 eyes/patients) and IVA (38 eyes/patients) groups. The median BCVA and CMT were significantly improved during the study period (p<0.001) with no significant intergroup differences. The ratio of 4-, 6-, 8-, 10-, and 12-week maximum treatment intervals were 28.6%, 17.1%, 14.3%, 8.6%, and 31.4% in the IVR, and 13.2%, 15.8%, 21.1%, 15.8%, and 34.2% in the IVA group (p=0.492). The median (IQR) number of injections in the IVA group (8 [7-9]) was significantly lower than the IVR group (9 [8-12]) during the one-year T&E period (p=0.026). The disease activity rates were 34.3% and 26.4% one month (p=0.610) and 37.1% and 21.1% one year (p=0.195) after the switch in IVR and IVA groups. This real-life comparison study indicates that, after the treatment failure with three loading doses of IVB, switching to either on-label anti-VEGF agent can be regarded as comparable considering functional and anatomical results. However, although maximum treatment intervals were not significantly different, fewer injections were required with aflibercept during the one-year T&E follow-up period.

Intravenous 3K3A-Activated Protein C Inhibits Murine Ocular Inflammation and Suppresses Ocular Choroidal Neovascularization

Introduction: Choroidal neovascularization (CNV) is characterized by the growth of newly formed abnormal blood vessels from the choroid extending into the neurosensory retina, leading to vision loss. CNV is a common cause of visual impairment in neovascular age-related macular degeneration (nAMD) patients. Current treatments failed to stop the continuity of the neurodegenerative process. Despite the urgency, no neuroprotective agent has been found yet to treat AMD and other neurodegenerative ocular diseases. 3K3A-activated protein C (APC) is a cell-signaling analog of the endogenous blood serine protease APC. Preclinical studies showed that circulating plasma 3K3A-APC readily crosses the blood-brain barrier (BBB) and reaches neurons due to EPCR-dependent transport. In rodent models of stroke, brain injury, and neurodegenerative disorders, 3K3A-APC exerts neuroprotective, anti-inflammatory, and vasculoprotective activities. Due to its pleiotropic effects, 3K3A-APC has advanced to clinical trial stages for treating acute brain damage and chronic neurodegenerative diseases, which share similarities with retinal neurodegenerative disorders. Notably, the retina is part of the central nervous system (CNS), and the blood-retina barrier shares functional and structural similarities with the BBB. We previously demonstrated that intraocular administration of 3K3A-APC functions as a pleiotropic cytoprotective molecule within the retina, reducing ocular inflammation, suppressing CNV growth, and exhibiting promising therapeutic potential as a neuroprotective agent for treating ocular disorders. Intraocular administration is commonly utilized for delivering therapeutics to treat retinal conditions. However, safety concerns, the burden on the healthcare system, and patient comfort may indicate that systemic administration of 3K3A-APC is a beneficial alternative. Aim: To determine whether intravenously injecting 3K3A-APC into mice tails will cross the blood-retina barrier, induce anti-inflammatory activities in the retina, and suppress CNV. Methods: The efficacy of systemic administration of 3K3A-APC was evaluated using two C57BL/6J murine models: the LPS-induced ocular inflammation and the laser-induced CNV model. CNV was triggered by laser and ocular inflammation was triggered by intravitreal injection of lipopolysaccharide (LPS). Murine recombinant 3K3A-APC was administered systemically via tail injection. Fluorescein isothiocyanate (FITC)-dextran perfusion followed by retinal flatmount staining with anti-CD11b was used to assess inflammatory co-localization of cells to retinal vessels. FITC-dextran perfusion followed by retinal pigment epithelium (RPE)-choroid flatmount was used to assess CNV vascular penetration using 3D confocal imaging. Results: LPS injection triggered robust inflammatory cell infiltration in both the anterior and posterior chambers of the eyes. Systemic administration of 3K3A-APC (0.5 mg/kg, 1 and 4 hours post-LPS) significantly inhibited ocular inflammation. Immunostaining performed 24 hours post LPS revealed that 3K3A-APC reduced the number of CD11b+ monocyte and their extravasation into the retinal parenchyma (Figure). In the laser-induced CNV model, systemic administration of 0.2 mg/kg 3K3A-APC was applied one hour and four days post-laser. Evaluation of retinal specimens ten days post-laser showed that 3K3A-APC treatment significantly suppressed CNV growth, attenuated the abnormal growth of blood vessels from the choroid into the sensory retina, and decreased myeloid cell recruitment to the RPE-choroid area. Conclusion: Our study reveals that systemically administered 3K3A-APC effectively inhibits ocular inflammation and reduces CNV formation. Drawing insights from the neuroprotective activities of 3K3A-APC in the brain and CNS and recognizing the retina, particularly the macula, as an extension of the brain, we propose 3K3A-APC as a potential neuroprotective treatment for AMD and other neurodegenerative retinal pathologies. Given the established safety of systemic 3K3A-APC administration in phase 2 clinical trials for ischemic stroke, our findings support further exploring 3K3A-APC as a novel therapeutic approach in ophthalmology. Further research is warranted to elucidate fully the mechanisms underlying 3K3A-APC's beneficial effects on the retina.

Treatment Methods Dry Form of Age Macular Degeneration — History and Prospects. Review

Age related macular degeneration is a leading cause of vision loss and an increasing problem of disability throughout the world among adults. That revue covers historical points, risk factors, pathogenesis, classification and current treatment ways of that pathology. The causes of age-related macular degeneration are not fully understood, in spite of keeping a great amount of knowledge at etiology, pathogenesis, diagnosis and modern types of treatment. The problem of age-related macular degeneration treatment has remained actual nowadays. Now, the medicine doesn’t have etiotropic treatment of AMD, because we still don’t know a definite etiologic factor of this developing disease. The main treatment for wet AMD is the injection of medications called anti-VEGF agents. Currently, treatment of dry age-related macular degeneration includes modification of risk factors (stop smoking, healthy life style and etc) and dietary supplements containing a combination of certain ingredients (vitamin C, vitamin E, zinc, copper, and lutein with zeaxanthin or beta-carotene) may be able to slow the progression of the disease. The disadvantage of current treatment methods is a narrow focus at one of the pathogenesis components or using as symptomatic therapy. The analysis of literature date has allowed noticing of using of an extracorporeal hemocorrection as perspective way at exploration of new methods of treatment of dry age-related macular degeneration.

Biomaterials used for tissue engineering of barrier-forming cell monolayers in the eye.

Cell monolayers that form a barrier between two structures play an important role for the maintenance of tissue functionality. In the anterior portion of the eye, the corneal endothelium forms a barrier that controls fluid exchange between the aqueous humor of the anterior chamber and the corneal stroma. This monolayer is central in the pathogenesis of Fuchs endothelial corneal dystrophy (FECD). FECD is a common corneal disease, in which corneal endothelial cells deposit extracellular matrix that increases the thickness of its basal membrane (Descemet's membrane), and forms excrescences (guttae). With time, there is a decrease in endothelial cell density that generates vision loss. Transplantation of a monolayer of healthy corneal endothelial cells on a Descemet membrane substitute could become an interesting alternative for the treatment of this pathology. In the back of the eye, the retinal pigment epithelium (RPE) forms the blood-retinal barrier, controlling fluid exchange between the choriocapillaris and the photoreceptors of the outer retina. In the retinal disease dry age-related macular degeneration (dry AMD), deposits (drusen) form between the RPE and its basal membrane (Bruch's membrane). These deposits hinder fluid exchange, resulting in progressive RPE cell death, which in turn generates photoreceptor cell death, and vision loss. Transplantation of a RPE monolayer on a Bruch's membrane/choroidal stromal substitute to replace the RPE before photoreceptor cell death could become a treatment alternative for this eye disease. This review will present the different biomaterials that are proposed for the engineering of a monolayer of corneal endothelium for the treatment of FECD, and a RPE monolayer for the treatment of dry AMD.

Geomorphic-based mine rehabilitation coupled with AMD chemical stabilisation in sulphide-rich ore deposits and soils: insights from a pioneering intervention at the Lousal mine, Iberian pyrite Belt

ABSTRACT The Lousal mine rehabilitation project proactively planned strategic milestones around key local geomorphic landforms and geochemical characteristics. GeoFluv™ method was used to design a rehabilitation topography mimicking natural landforms, on which a built-up soil cover with chemical buffering capabilities and open limestone channels were implemented across the intervention areas. Once these landform restoration works were completed, positive effects are observed in March 2022, with the native vegetation cover (the third main component of the restoration plan) established in most of the recovered area and a visible water quality improvement to the AMD treatment system water. Potentially Toxic Elements (PTEs) concentrations have reduced significantly after the reclamation actions, especially Fe (404 to 34 mg L−1), Zn (65.7 to 15.8 mg L−1) and Cd (122 to 0.8 µg L−1) concentrations. Minor problems detected have been processes of rill erosion associated with the inflow of adjacent watersheds, and the creation of ephemeral reducing conditions resulting from the leaching of the organic amendment of the topsoil. The Lousal mine reclamation project is the first built example in Europe where the concept of geomorphic reclamation has been combined with geochemical remediation in an area with intense acid mine drainage formation. Detailed monitoring of this project’s restorative progression throughout 2024 and beyond, should offer learning opportunities and innovations which will benefit future rehabilitation projects, with comparable underlying features.