Frontiers in ophthalmology最新文献

{"title":"Gene therapy for inherited retinal diseases: exploiting new tools in genome editing and nanotechnology","authors":"Cláudia Carvalho, Luísa Lemos, Pedro Antas, Miguel C. Seabra","doi":"10.3389/fopht.2023.1270561","DOIUrl":"https://doi.org/10.3389/fopht.2023.1270561","url":null,"abstract":"Inherited retinal diseases (IRDs) encompass a diverse group of genetic disorders that lead to progressive visual impairment and blindness. Over the years, considerable strides have been made in understanding the underlying molecular mechanisms of IRDs, laying the foundation for novel therapeutic interventions. Gene therapy has emerged as a compelling approach for treating IRDs, with notable advancements achieved through targeted gene augmentation. However, several setbacks and limitations persist, hindering the widespread clinical success of gene therapy for IRDs. One promising avenue of research is the development of new genome editing tools. Cutting-edge technologies such as CRISPR-Cas9 nucleases, base editing and prime editing provide unprecedented precision and efficiency in targeted gene manipulation, offering the potential to overcome existing challenges in gene therapy for IRDs. Furthermore, traditional gene therapy encounters a significant challenge due to immune responses to viral vectors, which remain crucial obstacles in achieving long-lasting therapeutic effects. Nanotechnology has emerged as a valuable ally in the quest to optimize gene therapy outcomes for ocular diseases. Nanoparticles engineered with nanoscale precision offer improved gene delivery to specific retinal cells, allowing for enhanced targeting and reduced immunogenicity. In this review, we discuss recent advancements in gene therapy for IRDs and explore the setbacks that have been encountered in clinical trials. We highlight the technological advances in genome editing for the treatment of IRDs and how integrating nanotechnology into gene delivery strategies could enhance the safety and efficacy of gene therapy, ultimately offering hope for patients with IRDs and potentially paving the way for similar advancements in other ocular disorders.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135107267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial to mesenchymal cell transition in diabetic retinopathy: targets and therapeutics.","authors":"Wasef Nijim, Mohamed Moustafa, Julia Humble, Mohamed Al-Shabrawey","doi":"10.3389/fopht.2023.1230581","DOIUrl":"10.3389/fopht.2023.1230581","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a result of neurovacular insults from hyperglycemia in diabetes mellitus (DM), and it is one of the top causes of vision loss throughout the modern world. This review article explores the role endothelial to mesenchymal transition (EndMT) has on the pathogenesis of DR. EndMT contributes to the disruption of the blood-retinal barrier, vascular leakage, neovascularization, and fibrosis observed in DR. Risk factors and biomarkers associated with DR severity are discussed, highlighting the importance of early detection and targeted therapies. Current treatments primarily focus on anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation. However, emerging therapeutic strategies aimed at inhibiting EndMT and its downstream effects show promise in preventing the development and progression of DR. Understanding the molecular and cellular mechanisms underlying EndMT in DR provides valuable insights into the disease process and offers potential options for the development of potential treatments.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82940529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spaceflight contrast sensitivity hypothesis and its role to investigate the pathophysiology of spaceflight-associated neuro-ocular syndrome.","authors":"Ethan Waisberg, Joshua Ong, Nasif Zaman, Phani Paladugu, Sharif Amit Kamran, Alireza Tavakkoli, Andrew G Lee","doi":"10.3389/fopht.2023.1229748","DOIUrl":"10.3389/fopht.2023.1229748","url":null,"abstract":"","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85247468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in high-resolution imaging of the iridocorneal angle.","authors":"Matthew J Keller, Thomas J Gast, Brett J King","doi":"10.3389/fopht.2023.1229670","DOIUrl":"10.3389/fopht.2023.1229670","url":null,"abstract":"<p><p>High-resolution imaging methods of the iridocorneal angle (ICA) will lead to enhanced understanding of aqueous humor outflow mechanisms and a characterization of the trabecular meshwork (TM) morphology at the cellular level will help to better understand glaucoma mechanics (e.g., cellular level biomechanics of the particulate glaucomas). This information will translate into immense clinical value, leading to more informed and customized treatment selection, and improved monitoring of procedural interventions that lower intraocular pressure (IOP). Given ICA anatomy, imaging modalities that yield intrinsic optical sectioning or 3D imaging capability will be useful to aid in the visualization of TM layers. This minireview examines advancements in imaging the ICA in high-resolution.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84498654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital optic disc pits and optic disc pit maculopathy: a review.","authors":"Ali Esmaeil, Ali Ali, Salman Almutairi, Khaled Alkandari, Raed Behbehani, Alaa Alali","doi":"10.3389/fopht.2023.1222979","DOIUrl":"10.3389/fopht.2023.1222979","url":null,"abstract":"<p><p>Optic disc pits are a rare but significant anomaly of the optic nerve head that can lead to visual impairment and associated complications. These pits are characterized by a small, oval-shaped depression in the disc, which can cause fluid accumulation and subsequent damage to the adjacent retina. Although the etiology and pathogenesis of optic disc pits are not fully understood, several theories have been proposed, including abnormal embryonic development and degenerative changes. Diagnosis is typically made through a comprehensive eye examination, including a dilated fundus exam and optical coherence tomography. Management options vary depending on the severity of the condition and associated complications, ranging from observation to surgical intervention.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81655132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis.","authors":"Grace E Nipp, Terry Lee, Kubra Sarici, Goldis Malek, Majda Hadziahmetovic","doi":"10.3389/fopht.2023.1237788","DOIUrl":"10.3389/fopht.2023.1237788","url":null,"abstract":"<p><p>Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals. There is much that is unknown regarding this disease's epidemiology, risk factors for development, and rate of progression through its four stages. Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD. These imaging advancements also offer new ways of differentiating AOFVD from phenotypically similar retinal diseases like age-related macular degeneration and Best disease. This review synthesizes the most recent discoveries regarding imaging correlates within AOFVD as well as risk factors for the development of AOFVD, complications of AOFVD, and treatment options. Our aim is to provide ophthalmologists a succinct resource so that they may offer clarity, guidance, and appropriate monitoring and treatments for their patients with suspected AOFVD.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83937715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rod-cone signal interference in the retina shapes perception in primates","authors":"Adree Songco-Aguas, William N. Grimes, Fred Rieke","doi":"10.3389/fopht.2023.1230084","DOIUrl":"https://doi.org/10.3389/fopht.2023.1230084","url":null,"abstract":"Linking the activity of neurons, circuits and synapses to human behavior is a fundamental goal of neuroscience. Meeting this goal is challenging, in part because behavior, particularly perception, often masks the complexity of the underlying neural circuits, and in part because of the significant behavioral differences between primates and animals like mice and flies in which genetic manipulations are relatively common. Here we relate circuit-level processing of rod and cone signals in the non-human primate retina to a known break in the normal seamlessness of human vision – a surprising inability to see high contrast flickering lights under specific conditions. We use electrophysiological recordings and perceptual experiments to identify key mechanisms that shape the retinal integration of rod- and cone-generated retinal signals. We then incorporate these mechanistic insights into a predictive model that accurately captures the cancellation of rod- and cone-mediated responses and can explain the perceptual insensitivity to flicker.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135154482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of 'dropless vitrectomy surgery' and comparison of outcomes to standard of care topical therapy.","authors":"K V Chalam, Harris Ahmed","doi":"10.3389/fopht.2023.1215968","DOIUrl":"10.3389/fopht.2023.1215968","url":null,"abstract":"<p><strong>Objective/background: </strong>To compare the effectiveness of intravitreal injection of triamcinolone acetonide/moxifloxacin (Tri-Moxi) with the standard eye drop regimen for controlling postoperative inflammation, intraocular pressure, infections, macular thickness, and visual acuity (VA) in patients undergoing pars plana vitrectomy for various retinal disorders.</p><p><strong>Subject/methods: </strong>In this retrospective longitudinal study, patients who underwent vitrectomy using intravitreal Tri-Moxi at the end of surgery (Group 1) were compared with those who received standard topical steroid antibiotics (Group 2) in terms of intraocular inflammation, intraocular pressure, macular thickness based on optical coherence tomography, and visual acuity.</p><p><strong>Results: </strong>In total, 162 consecutive eyes (group 1 [81 eyes]; group 2 [82 eyes]) were included. VA improved by two lines in both groups at 90 days. In Group 1, preoperative VA (logMAR) was 0.92 (0.66) compared to 0.92 (0.75) in Group 2 (p = 1), while at 3 months, it was 0.61 (0.3) and 0.57 (0.3), respectively (p = 0.46). Group 1 showed superior outcomes concerning central foveal thickness. The average central foveal thickness CFT (µm) in group 2 preoperatively was 423 (95) and 348 (63) at 3 months compared to group 1 526 (109) and 306 (108) preoperatively and 3 months, respectively (p = 0.042). There was no statistically significant difference in the rate of elevated intraocular pressure between the two groups or anterior chamber cell reaction severity, and no cases of endophthalmitis were observed in either group.</p><p><strong>Conclusions: </strong>Tri-Moxi is effective after vitrectomy and is not inferior to standard postoperative topical therapy.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72799752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scleral flaps, pars plana vitrectomy and gore-tex sutured posterior chamber intraocular lens placement: a case series and review of literature.","authors":"Pasquale Napolitano, Mariaelena Filippelli, Marianna Carosielli, Ciro Costagliola, Roberto Dell'Omo","doi":"10.3389/fopht.2023.1147881","DOIUrl":"10.3389/fopht.2023.1147881","url":null,"abstract":"<p><strong>Introduction: </strong>Cataract surgery is one of the most common surgical procedures performed worldwide. Intraocular lens (IOL) implants are placed routinely in the capsular bag after successful cataract extraction. However, in the absence of adequate capsular support, IOL may be placed in the anterior chamber, fixated to the iris or fixated to the sclera. The purpose of this study is to report the clinical outcomes and safety profile of a trans-scleral sutured intraocular lens (IOL) technique using scleral flaps, vitrectomy, and Gore-Tex suture to place posterior chamber IOL.</p><p><strong>Methods: </strong>Retrospective, interventional case series of eyes undergoing scleral fixation of an IOL using Gore-Tex suture with concurrent vitrectomy. Ocular examination with the logarithm of the minimum angle of resolution visual acuity (logMAR BCVA), tonometry, and slit-lamp biomicroscopy was performed on all patients at 1, 3, 6, and 12 months after the operation. All post-operative complications were recorded.</p><p><strong>Results: </strong>Twenty-five eyes of 25 patients were included. Mean logMAR BCVA improved from 0.43 ± 0.36 (2040 Snellen equivalent) preoperatively to 0.13 ± 0.18 (2025 Snellen equivalent) postoperatively at 12 months (p<0.01). Indications included surgical aphakia (16) and dislocated lens implant (9). No cases of IOL opacification, suprachoroidal haemorrhage, post-operative endophthalmitis, IOL dislocation, Gore-Tex exposure, or retinal detachment were observed during the follow-up period.</p><p><strong>Conclusion: </strong>Ab externo scleral fixation of IOLs with Gore-Tex suture plus scleral flap is well tolerated and associated with a very low rate of suture exposition. Moreover, our study confirms excellent refractive outcomes after surgery.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88516509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease.","authors":"David M Linn","doi":"10.3389/fopht.2023.1190439","DOIUrl":"10.3389/fopht.2023.1190439","url":null,"abstract":"<p><p>The role of acetylcholine (ACh) in visual processing in the mammalian retina has been the focus of research for many decades. Pioneering work on the localization of ACh discovered that the neurotransmitter is synthesized and stored in a distinct subpopulation of amacrine (starburst) cells. It has been shown that ACh release is regulated to a low resting \"tonic\" level, much like what is observed at the neuromuscular junction (NMJ). If there were a dysfunction in the tonic release of ACh, might post-synaptic changes render the targets of ACh [i.e., retinal ganglion cells (RGCs)] vulnerable to disease? During my time at Pharmacia & Upjohn (PNU), selective nicotinic ACh receptor (nAChR) agonists (e.g., PNU-282987) were developed as a possible therapy for central nervous system (CNS) diseases. As RGCs are the main targets of neurodegeneration in glaucoma, could the activation of this target provide neuroprotection? In response to this question, experiments to identify alpha7 nAChRs in the retina (i.e., target ID studies) followed by \"proof-of-concept\" experiments were conducted. Target ID studies included binding studies with retinal homogenates, [¹²⁵I]-alpha-bungarotoxin (α-BTX) autoradiography, and fluorescently tagged α-BTX binding in retinal slices. Imaging studies of intracellular calcium dynamics in the retinal slice were conducted. Reverse transcription-polymerase chain reaction (RT-PCR) analysis with alpha7 nAChR knockout mice using the \"laser-capture microdissection\" technique, <i>in situ</i> hybridization studies, and RT-PCR analysis of the human retina were conducted. Collectively, these experiments confirmed the presence of alpha7 nAChRs on specific cells in the retina. \"Proof-of-concept\" neuroprotection studies demonstrated that PNU-282987 provided significant protection for RGCs. This protection was dose dependent and was blocked with selective antagonists. More recently, evidence for the generation of new RGCs has been reported with PNU-282987 in rodents. Interestingly, the appearance of new RGCs is more pronounced with eye-drop application than with intravitreal injection. One could postulate that this reflects the neurogenic activation of alpha7 receptors on the retinal pigment epithelium (RPE) (eye drops) vs. a neuroprotective effect on RGCs (injections). In conclusion, there does appear to be a cholinergic retinal \"tone\" associated with RGCs that could be utilized as a neuroprotective therapy. However, a distinct cholinergic neurogenic mechanism also appears to exist in the outer retina that could possibly be exploited to generate new RGCs lost through various disease processes.</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79532605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}