Journal of Ocular Pharmacology and Therapeutics最新文献

{"title":"Inhibition of Experimental Corneal Neovascularization by the Tight Junction Protein ZO-1.","authors":"Qingying Yao, Hongya Wu, Hang Ren, Jiufa Cao, Ying Shao, Gaoqin Liu, Peirong Lu","doi":"10.1089/jop.2023.0162","DOIUrl":"10.1089/jop.2023.0162","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To explore the effects of the tight junction protein zonula occludens 1 (ZO-1) on experimental corneal neovascularization (CNV). <b><i>Methods:</i></b> CNV models were established in the left eyes of BALB/c mice using NaOH. Anti-ZO-1 neutralizing antibody was topically applied to the burnt corneas after modeling thrice a day for 1 week. CD31 expression was analyzed to calculate the ratio of CNV number to area using a corneal whole-mount fluorescent immunohistochemical assay. Messenger ribonucleic acid (mRNA) and protein expression levels of ZO-1, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), phosphorylated protein kinase C (pPKC), and clusterin in burned corneas were detected by reverse transcriptase polymerase chain reaction (PCR) and western blot analyses. Infiltration of neutrophils, macrophages, and progenitor cells was examined by flow cytometry. <b><i>Results:</i></b> CNV was obviously greater in 45 s than in 15 s alkali injury group. In another experiment, CNV was obviously greater in the ZO-1 antibody group than in the vehicle-treated group. Corneal mRNA and protein expression levels of VEGF, IL-1β, IL-6, IL-8, IL-18, and MCP-1 were significantly higher in the ZO-1 antibody group than in the control group. Infiltration of neutrophils, macrophages, and progenitor cells was significantly greater in the ZO-1 antibody group than in the control group. TNF-α expression was much higher in 45 s than in 15 s alkali injury group. However, protein expression of pPKC and clusterin was much lower in 45 s than in 15 s alkali injury group. <b><i>Conclusions:</i></b> Anti-ZO-1 neutralizing antibody-treated mice exhibited enhanced alkali-induced CNV through enhanced intracorneal infiltration of progenitor and inflammatory cells.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":"40 6","pages":"379-388"},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2024.0054","DOIUrl":"10.1089/jop.2024.0054","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"259-260"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Complexities of Severe Acute Respiratory Syndrome Coronavirus 2: A Comprehensive Ophthalmic and Systemic Perspective.","authors":"Piergiorgio Neri, Yanny Perez, Aniruddha Agarwal, Francesco Pichi","doi":"10.1089/jop.2024.0037","DOIUrl":"10.1089/jop.2024.0037","url":null,"abstract":"<p><p>The editorial explores the profound implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, which emerged in December 2019 and rapidly evolved into a global health crisis. Despite initial focus on respiratory symptoms, the virus revealed significant ocular implications, prompting a reevaluation of the eye's role in its transmission, diagnosis, and systemic effects. The paradoxical nature of SARS-CoV-2-simultaneously novel and familiar within the coronavirus family-has been central to guiding the global medical response, including the swift development of vaccines. The pandemic has intensified research into the eye's susceptibility to viral infections, enhancing our understanding of virus-host interactions and the systemic impacts of viral diseases. The editorial delves into the pathophysiology of SARS-CoV-2, highlighting its potential to trigger autoinflammatory and autoimmune reactions with significant ocular repercussions. It examines the rapid vaccine development and deployment, the associated ocular side effects, and the ongoing research necessary to mitigate these outcomes. As the World Health Organization declared the end of COVID-19 as a public health emergency, the focus has shifted toward understanding the virus's long-term implications, including its effects on ocular health. This work underscores the critical role of interdisciplinary collaboration in addressing the systemic impacts of viral infections. It emphasizes the importance of ophthalmology in the broader context of public health and highlights the need for continued vigilance, research, and adaptation in a postpandemic world. The editorial calls for an integrated approach to health care, emphasizing the lessons learned from the SARS-CoV-2 pandemic to prepare for future health challenges, with a particular focus on the intersection of virology, immunology, and ophthalmology.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"253-258"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AG-920 (Articaine) Ophthalmic Solution: A Masked, Active-Controlled Evaluation of Its Local Anesthetic Efficacy and Safety in Pediatric Patients.","authors":"Victor H Gonzalez, Martin Uram, Audrey Schupp, Michelle Widmann, Gary D Novack","doi":"10.1089/jop.2023.0187","DOIUrl":"10.1089/jop.2023.0187","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> The safety and efficacy of a novel topical ocular anesthetic (AG-920 sterile ophthalmic solution, 8%) was previously evaluated in adults. For both clinical and regulatory purposes, this new agent was evaluated in children. <b><i>Methods:</i></b> This was a Phase 3, randomized, active-controlled, single-masked, parallel-group design study in healthy pediatric subjects performed at a private practice retina clinic in the United States. The safety and anesthetic efficacy of AG-920 was compared with proparacaine hydrochloride ophthalmic solution 0.5% in 60 children undergoing ophthalmic examinations. The primary efficacy endpoint was whether the investigator was able to perform the eye examination. <b><i>Results:</i></b> In all subjects in each treatment group, the investigator was able to perform the eye examination without additional local anesthetic. There were no adverse events reported in this study. In both the study eye and fellow eye, there were no notable changes after dosing, and both treatment groups were similar. All external eye exams in all subjects in both treatment groups were normal. <b><i>Conclusions:</i></b> In this pediatric population aged 7 months to >11 years, AG-920 was therapeutically equivalent to marketed proparacaine with respect to having an ophthalmic examination performed without needing additional local anesthetic. Further, AG-920 was well tolerated, and there were no clinically significant safety findings.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"293-296"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical Emulsions: A Viable Approach for Ocular Drug Delivery.","authors":"Amol Chhatrapati Bisen, Saurabh Srivastava, Anjali Mishra, Sachin Nashik Sanap, Arpon Biswas, Abhijit Deb Choudhury, Ayush Dubey, Neeraj Mohan Gupta, Karan Singh Yadav, Madhav Nilakanth Mugale, Rabi Sankar Bhatta","doi":"10.1089/jop.2023.0166","DOIUrl":"10.1089/jop.2023.0166","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"261-280"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain.","authors":"Ansa Anam, Chang Liu, Louis Tong, Yu-Chi Liu","doi":"10.1089/jop.2023.0155","DOIUrl":"10.1089/jop.2023.0155","url":null,"abstract":"<p><p>Blood-derived preparations, including autologous or allogenic serum, umbilical cord serum/plasma, and platelet-rich plasma eye drops, contain various growth factors, cytokines, and immunoglobulins that resemble natural tears. These components play important roles in corneal cell migration, proliferation, and wound healing. Blood-derived eye drops have demonstrated clinical effectiveness across a spectrum of ocular surface conditions, encompassing dry eye disease, Sjögren's syndrome, graft-versus-host disease, and neuropathic corneal pain (NCP). Currently, management of NCP remains challenging. The emergence of blood-derived eye drops represents a promising therapeutic approach. In this review, we discuss the benefits and limitations of different blood-derived eye drops, their mechanisms of action, and treatment efficacy in patients with NCP. Several studies have demonstrated the clinical efficacy of autologous serum eye drops in relieving pain and pain-like symptoms, such as allodynia and photoallodynia. Corneal nerve parameters were also significantly improved, as evidenced by increased nerve fiber density, length, nerve reflectivity, and tortuosity, as well as a decreased occurrence of beading and neuromas after the treatment. The extent of nerve regeneration correlated with improvement in patient-reported photoallodynia. Cord plasma eye drops also show potential for symptom alleviation and corneal nerve regeneration. Future directions for clinical practice and research involve standardizing preparation protocols, establishing treatment guidelines, elucidating underlying mechanisms, conducting long-term clinical trials, and implementing cost-effective measures such as scaling up manufacturing. With ongoing advancements, blood-derived eye drops hold promise as a valuable therapeutic option for patients suffering from NCP.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"281-292"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.","authors":"Susan S Lee, Saumya Nagar, Lakshmi Rajagopalan, Werhner Orilla, Karl G Csaky, Alexandra Almazan, Liuqing Yang, Michael R Robinson","doi":"10.1089/jop.2023.0100","DOIUrl":"10.1089/jop.2023.0100","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. <b><i>Methods:</i></b> Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. <b><i>Results:</i></b> Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. <b><i>Conclusions:</i></b> Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"297-308"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Solanum nigrum</i> Toxicity and Its Neuroprotective Effect Against Retinal Ganglion Cell Death Through Modulation of Extracellular Matrix in a Glaucoma Rat Model.","authors":"Karan Singh Yadav, Amol Chhatrapati Bisen, Sharmeen Ishteyaque, Isha Sharma, Smriti Verma, Sachin Nashik Sanap, Shobhit Verma, Kaveri R Washimkar, Akhilesh Kumar, Vineeta Tripathi, Rabi Sankar Bhatta, Madhav Nilakanth Mugale","doi":"10.1089/jop.2023.0089","DOIUrl":"10.1089/jop.2023.0089","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Glaucoma is a complex degenerative optic neuropathy characterized by loss of retinal ganglion cells (RGCs) leading to irreversible vision loss and blindness. <i>Solanum nigrum</i> has been used for decades in traditional medicine system. However, no extensive studies were reported on its antiglaucoma properties. Therefore, this study was designed to investigate the neuroprotective effects of <i>S. nigrum</i> extract on RGC against glaucoma rat model. <b><i>Methods:</i></b> High performance liquid chromatography and liquid chromatography tandem mass spectrometry was used to analyze the phytochemical profile of aqueous extract of <i>S. nigrum</i> (AESN). <i>In vitro</i>, {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} (MTT) and H₂DCFDA assays were used to determine cell viability and reactive oxygen species (ROS) production in Statens Seruminstitut Rabbit Cornea cells. <i>In vivo</i>, AESN was orally administered to carbomer-induced rats for 4 weeks. Intraocular pressure, antioxidant levels, and electrolytes were determined. Histopathological and immunohistochemical analysis was carried out to evaluate the neurodegeneration of RGC. <b><i>Results:</i></b> MTT assay showed AESN exhibited greater cell viability and minimal ROS production at 10 μg/mL. Slit lamp and funduscopy confirmed glaucomatous changes in carbomer-induced rats. Administration of AESN showed minimal peripheral corneal vascularization and restored histopathological alterations such as minimal loss of corneal epithelium and moderate narrowing of the iridocorneal angle. Immunohistochemistry analysis showed increased expression of positive BRN3A cells and decreased matrix metalloproteinase (MMP)-9 activation in retina and cornea, whereas western blot analysis revealed downregulation of extracellular matrix proteins (COL-1 and MMP-9) in AESN-treated rats compared with the diseased group rats. <b><i>Conclusions:</i></b> AESN protects RGC loss through remodeling of MMPs and, therefore, can be used for the development of novel neurotherapeutics for the treatment of glaucoma.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"309-324"},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Various Concentrations of Low-Dose Atropine on Pupillary Diameter and Accommodative Amplitude in Children with Myopia.","authors":"Huy D M Tran, Thao T X Ha, Yen H Tran, Minas Coroneo, Tuan D Tran, Trang U Truong, Padmaja Sankaridurg","doi":"10.1089/jop.2023.0173","DOIUrl":"10.1089/jop.2023.0173","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To assess over 2 weeks, the effect of 3 different low concentrations of atropine on pupillary diameter and accommodative amplitude in children with myopia. <b><i>Methods:</i></b> Fifty-eight children with myopia [spherical equivalent (SE) of -0.50 diopters (D) or worse, astigmatism of less than or equal to 2.00 D] were randomly allocated to 3 groups receiving 0.01%, 0.02%, or 0.03% atropine eye drops, once nightly for 2 weeks. The primary outcome was the change from baseline in pupillary diameter and accommodative amplitude with each of the concentrations. <b><i>Results:</i></b> Fifty-seven participants (114 eyes), aged between 6 and 12 years, completed the 2-week trial (mean age 9.3 ± 1.7 years and mean SE -3.53 ± 1.79 D). After 2 weeks of use, all the 3 concentrations were found to have a statistically significant effect on both the pupillary diameter and accommodative amplitude. Accommodative amplitude reduced by an average of 5.23 D, 9.28 D, and 9.32 D, and photopic pupil size increased by an average of 0.95 ± 1.05 mm, 1.65 ± 0.93 mm, and 2.16 ± 0.88 mm with 0.01%, 0.02%, and 0.03%, respectively. Of the eyes, a total of 5.3% and 5.9% of the eyes on 0.02% and 0.03% atropine had a mean residual accommodative amplitude of <5 D. The percentage of eyes having a pupillary dilation >3 mm were 4.8%, 10.5%, and 23.5% for 0.01%, 0.02%, and 0.03% atropine, respectively. <b><i>Conclusions:</i></b> Low-dose atropine had an effect on pupillary diameter and accommodative amplitude. With the highest concentration assessed, that is, 0.03% nearly 1 of 4 eyes had pupillary dilation of >3 mm. Clinical Trial Registration number: NCT03699423.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"232-239"},"PeriodicalIF":1.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Treatment Effects of Conditioned Medium from Human Orbital Adipose-Derived Stem Cells in a Corneal Alkali Burn Rabbit Model.","authors":"Yu Cheng, Guangpeng Liu","doi":"10.1089/jop.2023.0154","DOIUrl":"10.1089/jop.2023.0154","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> This study aimed to evaluate the effects of a new treatment-conditioned medium from human orbital adipose-derived stem cells (OASC-CM)-on corneal recovery after alkali burns in a rabbit model. <b><i>Methods:</i></b> The corneal alkali burn rabbit model was established and treated with OASC-CM, conditioned medium from human abdominal subcutaneous adipose-derived stem cells (ABASC-CM), and fresh control culture medium (con-CM) three times a day for 7 days, respectively. Subsequently, the treatment effects were evaluated and compared through clinical, histological, immunohistochemical, and cytokine evaluations. <b><i>Results:</i></b> Clinically, OASC-CM alleviated corneal opacity and edema and promoted recovery of corneal epithelium defect. Histologically and immunohistochemically, OASC-CM inhibited neovascularization, conjunctivalization, and immuno-inflammatory reaction, while promoting corneal regeneration and rearrangement. Increased secretion of interleukin-10 and inhibited protein levels of cluster of differentiation 45, interferon-γ, and tumor necrosis factor-α were observed in the alkali-burned cornea after OASC-CM treatment, which might be the relevant molecular mechanism. <b><i>Conclusions:</i></b> OASC-CM showed significant effects on the recovery of rabbit corneal alkali burns and eliminated immunological and ethical limitations, representing a new option for corneal wound treatment.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"222-231"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}