Treatment Of Retinal Diseases Research Articles

Therapeutic Effects of Anti-Inflammatory and Anti-Oxidant Nutritional Supplementation in Retinal Ischemic Diseases

Appropriate nutrients are essential for cellular function. Dietary components can alter the risk of systemic metabolic diseases, including cardiovascular diseases, cancer, diabetes, and obesity, and can also affect retinal diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. Dietary nutrients have been assessed for the prevention or treatment of retinal ischemic diseases and the diseases of aging. In this article, we review clinical and experimental evidence concerning the potential of some nutritional supplements to prevent or treat retinal ischemic diseases and provide further insights into the therapeutic effects of nutritional supplementation on retinopathies. We will review the roles of nutrients in preventing or protecting against retinal ischemic diseases.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Генная терапия наследственных заболеваний сетчатки

This scientific literature review demonstrates high prospects of recent developments in gene therapy for the treatment of retinal diseases. First of all it concerns inherited pathologies such as retinitis pigmentosa and Leber congenital amaurosis. Nevertheless gene therapy is still quite far from its tangible application in clinical practice for other retinal diseases, although preliminary trial outcomes of its use for some of them (for example, achromatopsia, congenital X-linked retinoschisis) turn to be very promising. The data presented in this review inspire hope that gene therapy will be more accessible and widely-used in clinical practice. Key words:retinal diseases, inherited retinal diseases, gene therapy, voretigene neparvovec

Efficient retinal ganglion cells transduction by retro-orbital venous sinus injection of AAV-PHP.eB in mature mice

Gene therapy is one of the strategies that may reduce or reverse progressive neurodegeneration in retinal neurodegenerative diseases. However, efficiently delivering transgenes to retinal ganglion cells (RGCs) remains hard to achieve. In this study, we innovatively investigated transduction efficiency of adeno-associated virus (AAV)-PHP.eB in murine RGCs by retro-orbital venous sinus injection. Five doses of AAV-PHP.eB-EGFP were retro-orbitally injected in venous sinus in adult C57/BL6J mice. Two weeks after administration, RGCs transduction efficiency was quantified by retinal flat-mounts and frozen section co-labeling with RGCs marker Rbpms. In addition, safety of this method was evaluated by RGCs survival rate and retinal morphology. To conform efficacy of this new method, AAV-PHP.eB-CNTF was administrated into mature mice through single retro-orbital venous injection after optic nerve crush injury to evaluate axonal elongation. Results indicated that AAV- PHP.eB readily crossed the blood-retina barrier and was able to transduce more than 90% of RGCs when total dose of virus reached 5×1010 vector genomes (vg). Moreover, this technique did not affect RGCs survival rate and retinal morphology. Furthermore, retro-orbital venous delivery of AAV-PHP.eB-CNTF effectively transduced RGCs, robustly promoted axonal regeneration after optic nerve crush injury. Thus, novel AAV-PHP.eB retro-orbital injection provides a minimally invasive and efficient route for transgene delivery in treatment of retinal neurodegenerative diseases.

Suppression of retinal neovascularization by intravitreal injection of cryptotanshinone

Neovascular eye diseases, including proliferative diabetic retinopathy and retinopathy of prematurity, is a major cause of blindness. Laser ablation and intravitreal anti-VEGF injection have shown their limitations in treatment of retinal neovascularization. Identification of a new therapeutic strategies is in urgent need. Our study aims to assess the effects of Cryptotanshinone (CPT), a natural compound derived from Salvia miltiorrhiza Bunge, in retina neovascularization and explore its potential mechanism. Our study demonstrated that CPT did not cause retina tissue toxicity at the tested concentrations. Intravitreal injections of CPT reduced pathological angiogenesis and promoted physical angiogenesis in oxygen-induced retinopathy (OIR) model. CPT improve visual function in OIR mice and reduced cell apoptosis. Moreover, we also revealed that CPT diminishes the expression of inflammatory cytokines in the OIR retina. In vitro, the administration of CPT effectively inhibited endothelial cells proliferation, migration, sprouting, and tube formation induced by the stimulation of human retinal vascular endothelial cells (HRVECs) with VEGF165. Mechanistically, CPT blocking the phosphorylation of VEGFR2 and downstream targeting pathway. After all, the findings demonstrated that CPT exhibits potent anti-angiogenic and anti-inflammatory effects in OIR mice, and it has therapeutic potential for the treatment of neovascular retinal diseases.

In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye.

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37°C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.

Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.

Assessment of intraocular pressure changes following intravitreal injections of three anti-VEGF agents

PurposeIntravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents has emerged as the primary treatment for prevalent retinal diseases. Despite its efficacy, IVI may induce intraocular pressure elevation due to vitreous fluid shifts. This study aims to compare the effects of three distinct anti-VEGF agents on intraocular pressure (IOP) elevation within a single clinic setting. DesignA prospective study, conducted at a single retinal clinic in a tertiary medical center (Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel). MethodsPatients receiving 3 different anti VEGF medications; bevacizumab, aflibercept, and ranibizumab, were examined. IOP was measured pre- and post-injection using an iCare Pro-tonometer. Demographic parameters and ocular characteristics were collected. ResultsThe study included 195 patients (average age 76.13 years; 100 males, 95 females). The medications administered were aflibercept (N = 70, 35 %), bevacizumab (N = 73, 37.4 %), and ranibizumab (N = 52, 26.7 %). In patients with a normal baseline intraocular pressure, no significant variance was observed in the post-injection versus pre-injection pressure change (delta) across medications. Conversely, in patients with higher pressure (>20 mmHg), aflibercept incited a more substantial increase than bevacizumab or ranibizumab. No correlation emerged between the pressure rise and age or lens status. ConclusionsNo significant difference was found in the increase of intraocular pressure following injection among different medications in patients with low-normal intraocular pressure. However, for patients prone to higher baseline pressure, caution is recommended with aflibercept due to a more pronounced increase. Further research is essential to comprehend the factors influencing pressure increase and their associated clinical implications.

Smart Nanocarriers for the Treatment of Retinal Diseases.

Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.

A spatiotemporal convolution recurrent neural network for pixel-level peripapillary atrophy prediction using sequential fundus images

The progression of peripapillary atrophy (PPA) is closely associated with the development of retinal diseases such as myopia and glaucoma. PPA prediction employing longitudinal images to obtain its progress trend can facilitate personalized treatment. Although existing studies have attempted to predict the persistence of PPA, such studies cannot provide quantitative measurement for personalized treatment. In this paper, we propose a spatiotemporal framework for pixel-level PPA prediction using sequential fundus images, including feature extractor, temporal memory, and spatiotemporal prediction modules. To take advantage of historical information, a temporal memory module is used, integrating current and prior features to build sequential data of features. To further enhance the prediction performance, the recurrent neural network states in a spatiotemporal prediction module transmit between different layers, enabling high-level states to guide the learning of low-level states. To handle missing data in clinical follow-up data, we use the predicted output of the spatiotemporal prediction module to substitute the missing data, and the scheduled-sampling strategy is employed in training. Extensive experiments conducted using a clinical dataset demonstrate that our proposed method achieves a satisfactory performance compared with the start-of-the-art models. The proposed approach can be applied using clinical data to obtain various quantitative indicators for personalized treatment and prevention of retinal disease.

Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.

Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].

Evaluation of Full-Field Stimulus Threshold Test Results in Retinitis Pigmentosa: Relationship with Full-Field Electroretinography, Multifocal Electroretinography, Optical Coherence Tomography, and Visual Field.

The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on full-field ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG.

Current use of aflibercept 8 mg (eylea HD) in retinal diseases

Aflibercept 8 mg (Eylea HD) has emerged as a pivotal agent in the treatment of retinal diseases and has begun to showcase its efficacy and innovation in the field of ophthalmology. This article delves into the current use of aflibercept 8 mg, exploring its applications, mechanisms of action, and impact on the treatment landscape for various retinal conditions. This review provides an overview of recent clinical studies and highlights the key findings and advancements associated with the use of 8 mg aflibercept.

Subthreshold laser treatment in retinal diseases: a mini review.

To summarize the mechanism and the clinical applications of subthreshold laser (STL) in retinal practice. Subthreshold or "non-destructive" laser includes all types of laser treatments that produce minimal or no damage to the tissues and no visible signs after application. A descriptive review of articles from literature databases (PubMed, Medline, Embase, Cochrane, Web of Science) published before August 2023, which discuss current STL treatments of retinal diseases. This review provides evidence for STL as a treatment option for central serous chorioretinopathy, diabetic retinopathy, age-related macular degeneration, macular edema due to retinal vein occlusion, and other maculopathies. In most published reports, STL has shown a therapeutic effect without damage to the underlying tissue. Subthreshold laser treatment has shown safety and efficacy in the management of some retinal and macular diseases. Stimulation of the retinal pigment epithelium without destroying adjacent neuroretina has been shown to be sufficient in inducing retinal repair in many clinical cases. Recent research and clinical studies continue to explore the mechanisms and improving therapeutic benefits of this technology as well as extend the range of retinal disorders treatable by this modality.

Multi-scale local-global transformer with contrastive learning for biomarkers segmentation in retinal OCT images

Quantitative analysis of biomarkers in Optical Coherence Tomography (OCT) images plays an import role in the diagnosis and treatment of retinal diseases. However, biomarker segmentation in retinal OCT images is very hard due to the large variations in size and shape of retinal biomarkers, blurred boundaries, low contrast, and speckle interference. We proposed a novel Multi-scale Local-Global Transformer network (MsLGT-Net) for biomarker segmentation in retinal OCT images. The network combines the proposed Multi-scale Fusion Attention (MFA) module, Local-Global Transformer (LGT) module, and Contrastive Learning Enhancement (CLE) module to tackle the challenges of biomarker segmentation. Specifically, the proposed MFA module aims to enhance the network’s ability to learn multi-scale features of retinal biomarkers by effectively combining the local detail information and contextual semantic information of biomarkers at different scales, and improve the representation ability for different classes of biomarkers. The LGT module is designed to learn local and global information adaptively from multi-scale fused features to address the challenge of small biomarker segmentation. In addition, to distinguish features between different types of retinal biomarkers, we propose the CLE module to enhance the feature representation of different biomarkers. Our proposed method is validated on one public dataset and one local dataset. The experimental results show that the proposed method is more effective than other state-of-the-art methods.

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases.

Paracellular permeability across epithelial and endothelial cells is, in large part, regulated by apical intercellular junctions also referred to as tight junctions (TJs). These junctions contribute to the spatial definition of different tissue compartments within organisms, separating them from the outside world as well as from inner compartments, with their primary physiological role of maintaining tissue homeostasis. TJs restrict the free, passive diffusion of ions and hydrophilic small molecules through paracellular clefts and are important for appropriate cell polarization and transporter protein localisation, supporting the controlled transcellular diffusion of smaller and larger hydrophilic as well as hydrophobic substances. This traditional diffusion barrier concept of TJs has been challenged lately, owing to a better understanding of the components that are associated with TJs. It is now well-established that mutations in TJ proteins are associated with a range of human diseases and that a change in the membrane fluidity of neighbouring cells can open possibilities for therapeutics to cross intercellular junctions. Nanotechnological approaches, exploiting ultrasound or hyperosmotic agents and permeation enhancers, are the paradigm for achieving enhanced paracellular diffusion. The other widely used transport route of drugs is via transcellular transport, allowing the passage of a variety of pro-drugs and nanoparticle-encapsulated drugs via different mechanisms based on receptors and others. For a long time, there was an expectation that lipidic nanocarriers and polymeric nanostructures could revolutionize the field for the delivery of RNA and protein-based therapeutics across different biological barriers equipped with TJs (e.g., blood-brain barrier (BBB), retina-blood barrier (RBB), corneal TJs, etc.). However, only a limited increase in therapeutic efficiency has been reported for most systems until now. The purpose of this review is to explore the reasons behind the current failures and to examine the emergence of synthetic and cell-derived nanomaterials and nanotechnological approaches as potential game-changers in enhancing drug delivery to target locations both at and across TJs using innovative concepts. Specifically, we will focus on recent advancements in various nanotechnological strategies enabling the bypassing or temporally opening of TJs to the brain and to the retina, and discuss their advantages and limitations.

Induction of human ESC-derived and adult primary multipotent limbal stem cells into retinal pigment epithelial cells and corneal stromal stem cells

Human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) therapies are promising alternatives for the treatment of retinal degenerative diseases caused by RPE degeneration. The generation of autologous RPE cells from human adult donors, which has the advantage of avoiding immune rejection and teratoma formation, is an alternative cell resource to gain mechanistic insight into and test potential therapies for RPE degenerative diseases. Here, we found that limbal stem cells (LSCs) from hESCs and adult primary human limbus have the potential to produce RPE cells and corneal stromal stem cells (CSSCs). We showed that hESC-LSC-derived RPE cells (LSC-RPE) expressed RPE markers, had a phagocytic function, and synthesized tropical factors. Furthermore, during differentiation from LSCs to RPE cells, cells became pigmented, accompanied by a decrease in the level of LSC marker KRT15 and an increase in the level of RPE marker MITF. The Wnt signaling pathway plays a role in LSC-RPE fate transition, promotes MITF expression in the nucleus, and encourages RPE fate transition. In addition, we also showed that primary LSCs (pLSCs) from adult human limbus similar to hESC-LSC could generate RPE cells, which was supported by the co-expression of LSC and RPE cell markers (KRT15/OTX2, KRT15/MITF), suggesting the transition from pLSC to RPE cells, and typical polygonal morphology, melanization, RPE cell marker genes expression (TYR, RPE65), tight junction formation by ZO-1 expression, and the most crucial phagocytotic function. On the other hand, both hESC-LSCs and pLSCs also differentiated into CSSCs (LSC-CSSCs) that expressed stem cell markers (PAX6, NESTIN), presented MSC features, including surface marker expression and trilineage differentiation capability, like those in human CSSCs. Furthermore, the capability of pLSC-CSSC to differentiate into cells expressing keratocyte marker genes (ALDH3A1, PTGDS, PDK4) indicated the potential to induce keratocytes. These results suggest that the adult pLSC is an alternative cell resource, and its application provides a novel potential therapeutic avenue for preventing RPE dysfunction-related retinal degenerative diseases and corneal scarring.

Brolucizumab and other anti‐VEGF induced intraocular inflammation

Anti‐vascular endothelial growth factor (VEGF) agents, such as bevacizumab, ranibizumab, and aflibercept, are widely used in the treatment of various retinal diseases. Recently, brolucizumab, a novel anti‐VEGF agent, has been introduced in the market for the treatment of neovascular age‐related macular degeneration. However, the use of some anti‐VEGF agents has been associated with an increased risk of intraocular inflammation.In particular, brolucizumab has been reported to be associated with a higher incidence of intraocular inflammation compared to other anti‐VEGF agents. The inflammation can manifest as anterior uveitis, vitritis, or even occlusive retinal vasculitis, and lead to severe and permanent visual loss in some cases. Although the exact mechanism of this phenomenon is not fully understood, it is believed to be related to the immune response triggered by the injection of foreign proteins into the eye.The clinical presentation of intraocular inflammation can range from mild symptoms, such as ocular discomfort and blurry vision, to severe visual loss. Prompt and appropriate management of intraocular inflammation is crucial to preserve vision in patients receiving anti‐VEGF agents. Early detection of inflammation and prompt initiation of anti‐inflammatory treatment can prevent further damage to the eye.In cases of mild to moderate inflammation, close monitoring and topical or systemic anti‐inflammatory medication may be sufficient to control the inflammation and prevent visual deterioration. Cessation of the causative anti‐VEGF treatment may be necessary to prevent further exacerbation of the inflammation. In such cases, the patient may need to be switched to an alternative treatment option for their underlying condition.Overall, clinicians should maintain a high level of vigilance for the development of intraocular inflammation in patients receiving anti‐VEGF therapy. Close monitoring, early detection, and appropriate management of inflammation can help preserve vision and minimize the potential complications associated with these agents.

Synergistic effect of mesenchymal stem cells and silver nanoparticles in the treatment of retinal degenerative diseases

Aims/Purpose: Retinal degenerative diseases represent one of the leading causes of visual loss. Mesenchymal stem cells (MSCs) provide potential option for the treatment of several type of pathologies, including ocular diseases. Moreover, silver nanoparticles (AgNPs) are currently widely used in various fields of medicine mainly due to their antibacterial and antiangiogenic properties. Several studies showed their beneficial but also harmful effect. However, there are limited information about the synergistic effect of AgNPs with MSC‐based therapies.Methods: Chronical retinal degeneration was induced in BALB/c mice by repeated intraperitoneal application of sodium iodate (NaIO3). MSCs, AgNPs or MSCs plus AgNPs were intravitreally injected 48 h before the last application of NaIO3. Retinas were isolated after additional 7 days and tested by RT‐PCR for the expression of genes for rhodopsin (photoreceptors), Iba‐1 (microglia/macrophages), IL‐1β and galectin‐3. The presence of MSCs stained with PKH‐26 was analysed by flow cytometry.Results: It was shown that MSCs and MSCs applied with AgNPs were still present in the retina on day 7 after application. In all treated groups, the expression of the gene for galectin‐3 was decreased in contrast to untreated control. However, co‐application of MSCs with AgNPs had limited effect on downregulation of Iba‐1 and IL‐1β in contrast to MSCs or AgNPs treated group.Conclusions: The application of MSCs and AgNPs modulated immune response in chronical retinal degeneration but co‐application of MSCs with AgNPs decreased immunoregulatory effects comparted with single‐component therapy. Thus, there is a need for more investigation focusing on potential changes in MSCs applied with AgNPs.

망막 혈관 질환에서 원형 RNA의 작용 기전 및 RNA 치료제로서의 가능성

Maintaining and preserving visual function became critical in this aging society. The number of patients with retinal vascular disease such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy is gradually increasing due to increased life expectancy, advancements in the technology of delivering premature babies, and complications due to eating habits. To treat these retinal vascular diseases, surgical intervention such as laser photocoagulation and anti-vascular endothelial growth factor (VEGF) drugs can be considered. However, these treatment options are accompanied by various complications and adverse effects. Thus, new treatments focusing on the pathogenesis of retinal vascular disease need to be developed. Various evidences suggest that circular RNA is involved in the pathogenesis of retinal disease. In this article, we discuss about currently used treatments of retinal vascular diseases and the emerging role of circular RNAs in the pathogenesis of retinal vascular diseases. Therefore, understanding the mechanism of circular RNA regulating retinal disease and developing therapeutics using these circular RNAs may offer novel treatment options to cure retinal vascular disease.