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1.
Surv Ophthalmol ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39270826

ABSTRACT

Retinal degeneration (RD) is a group of ocular diseases characterized by progressive photoreceptor apoptosis and visual impairment. Mitochondrial malfunction, excessive oxidative stress, and chronic activation of neuroglia collectively contribute to the development of RD. Currently, there is a lack of efficacious therapeutic interventions for RD. Stanniocalcin-1 (STC-1) is a promising candidate molecule to decelerate photoreceptor cell death. STC-1 is a secreted calcium/phosphorus regulatory protein that exerts diverse protective effects. Accumulating evidence suggests that STC-1 protects retinal cells from ischemic injury, oxidative stress, and excessive apoptosis through enhancing the expression of uncoupling protein-2 (UCP-2). Furthermore, STC-1 exerts its antiinflammatory effects by inhibiting the activation of microglia and macrophages, as well as the synthesis and secretion of proinflammatory cytokines, such as TNF-α, IL-1, and IL-6. By employing these mechanisms, STC-1 effectively shields the retinal photoreceptors and optic nerve, thereby slowing down the progression of RD. We summarize the STC-1-mediated therapeutic effects on the degenerating retina, with a particular focus on its underlying mechanisms. These findings highlight that STC-1 may act as a versatile molecule to treat degenerative retinopathy. Further research on STC-1 is imperative to establish optimal protocols for its clinical use.

2.
Mater Today Bio ; 27: 101126, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38994470

ABSTRACT

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

3.
Cell Biosci ; 14(1): 59, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725013

ABSTRACT

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

4.
Ageing Res Rev ; 97: 102308, 2024 06.
Article in English | MEDLINE | ID: mdl-38615894

ABSTRACT

Aging entails the deterioration of the body's organs, including overall damages at both the genetic and cellular levels. The prevalence of age-related ocular disease such as macular degeneration, dry eye diseases, glaucoma and cataracts is increasing as the world's population ages, imposing a considerable economic burden on individuals and society. The development of age-related ocular disease is predominantly triggered by oxidative stress and chronic inflammatory reaction. Heme oxygenase-1 (HO-1) is a crucial antioxidant that mediates the degradative process of endogenous iron protoporphyrin heme. It catalyzes the rate-limiting step of the heme degradation reaction, and releases the metabolites such as carbon monoxide (CO), ferrous, and biliverdin (BV). The potent scavenging activity of these metabolites can help to defend against peroxides, peroxynitrite, hydroxyl, and superoxide radicals. Other than directly decomposing endogenous oxidizing substances (hemoglobin), HO-1 is also a critical regulator of inflammatory cells and tissue damage, exerting its anti-inflammation activity through regulating complex inflammatory networks. Therefore, promoting HO-1 expression may act as a promising therapeutic strategy for the age-related ocular disease. However, emerging evidences suggest that the overexpression of HO-1 significantly contributes to ferroptosis due to its dual nature. Surplus HO-1 leads to excessive Fe2+ and reactive oxygen species, thereby causing lipid peroxidation and ferroptosis. In this review, we elucidate the role of HO-1 in countering age-related disease, and summarize recent pharmacological trials that targeting HO-1 for disease management. Further refinements of the knowledge would position HO-1 as a novel therapeutic target for age-related ocular disease.


Subject(s)
Aging , Eye Diseases , Heme Oxygenase-1 , Humans , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Aging/metabolism , Aging/genetics , Eye Diseases/metabolism , Animals , Oxidative Stress/physiology
5.
Pharmacol Res ; 203: 107159, 2024 May.
Article in English | MEDLINE | ID: mdl-38554790

ABSTRACT

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science).


Subject(s)
Cytokines , Eye Diseases , Humans , Cytokines/metabolism , Animals , Eye Diseases/therapy , Eye Diseases/drug therapy , Drug Delivery Systems/methods , Cell Encapsulation/methods
6.
Gels ; 10(3)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38534576

ABSTRACT

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

7.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 07.
Article in English | MEDLINE | ID: mdl-38004433

ABSTRACT

Molecular hydrogen (H2) is a colorless, odorless, and tasteless gas which displays non-toxic features at high concentrations. H2 can alleviate oxidative damage, reduce inflammatory reactions and inhibit apoptosis cascades, thereby inducing protective and repairing effects on cells. H2 can be transported into the body in the form of H2 gas, hydrogen-rich water (HRW), hydrogen-rich saline (HRS) or H2 produced by intestinal bacteria. Accumulating evidence suggest that H2 is protective against multiple ophthalmic diseases, including cataracts, dry eye disease, diabetic retinopathy (DR) and other fields. In particular, H2 has been tested in the treatment of dry eye disease and corneal endothelial injury in clinical practice. This medical gas has brought hope to patients suffering from blindness. Although H2 has demonstrated promising therapeutic potentials and broad application prospects, further large-scale studies involving more patients are still needed to determine its optimal application mode and dosage. In this paper, we have reviewed the basic characteristics of H2, and its therapeutic effects in ophthalmic diseases. We also focus on the latest progress in the administration approaches and mechanisms underlying these benefits.

8.
Sci Rep ; 13(1): 17131, 2023 10 10.
Article in English | MEDLINE | ID: mdl-37816867

ABSTRACT

To compare early diabetic retinopathy (DR) severity level and the abilities in detecting early DR lesions among conventional five-field, ultrawide-field (UWF) Optos, and UWF Clarus fundus imaging methods. This was a single-center, prospective, clinic-based, and comparative study. In total, 157 consecutive patients with diabetes mellitus were enrolled in this study. All patients underwent comprehensive ophthalmological examinations. Following mydriasis, each eye was examined with conventional five-field, UWF Optos, and UWF Clarus fundus imaging methods. The initial UWF images were overlaid with a template mask that obscured the retina, which created a five-field view from UWF images (covered UWF images). The covered UWF images were then graded, after which the template mask was removed, and the original UWF images were also evaluated. All images were graded using the International Clinical DR severity scale. DR grades were compared and analyzed by weighted kappa statistics among the three fundus imaging methods. In total, 157 consecutive patients with diabetes (302 eyes) were enrolled in this study. Weighted kappa statistics for agreement were 0.471 (five-field vs. covered Optos), 0.809 (five-field vs. covered Clarus), 0.396 (covered Optos vs. covered Clarus), 0.463 (five-field vs. Optos), 0.521 (five-field vs. Clarus 133°), 0.500 (five-field vs. Clarus 200°), 0.323 (Optos vs. Clarus 133°), and 0.349 (Optos vs. Clarus 200°). The area under curve of covered Clarus images was higher than that of conventional five-field images at three different thresholds. Compared with conventional five-field and Optos fundus imaging methods, Clarus fundus imaging methods exhibited excellent performance in assessing early DR severity. Thus, Clarus fundus imaging methods were superior for early detection of DR.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/pathology , Prospective Studies , Fundus Oculi , Retina/diagnostic imaging , Retina/pathology , Diagnostic Imaging , Fluorescein Angiography , Diabetes Mellitus/pathology
9.
Aging Dis ; 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37728589

ABSTRACT

Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials.

10.
Gels ; 9(7)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37504398

ABSTRACT

The human eye is a consolidated organ with delicate structures and unique immune privileges. Ocular diseases are intractable due to the intrinsic biological barriers within the eyeball. Hydrogels are excellent drug-carrying substances with soft material and excellent properties. They have been extensively used to deliver drugs into ocular tissue via iontophoresis devices. Ophthalmic iontophoresis is an electrochemical technique using tiny electrical currents to deliver drugs into the eye non-invasively. The early infantile iontophoresis technique often required long applying time to achieve therapeutic dose in the posterior ocular segment. The potential limitations in the initial drug concentration and the maximum safe currents would also impede the efficiency and safety of iontophoresis. Moreover, the poor patient compliance always leads to mechanical damage to the cornea and sclera during application. Advantageously, the flexible drug-carrying hydrogel can be in direct contact with the eye during iontophoresis, thereby reducing mechanical damage to the ocular surface. Moreover, the water absorption and adjustable permeability of hydrogels can reduce the electrochemical (EC) reactions and enhance the efficiency of iontophoresis. In this review, we focus on recent developments of hydrogels iontophoresis in ophthalmologic practice. Refinements of the knowledge would provide an outlook for future application of hydrogels in treating ocular disease.

11.
Genes Dis ; 10(2): 505-520, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37223523

ABSTRACT

There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.

12.
Eye (Lond) ; 37(17): 3558-3564, 2023 12.
Article in English | MEDLINE | ID: mdl-37120657

ABSTRACT

PURPOSE: This study compared the efficiency of diabetic retinopathy (DR) diagnosis and differences in the relative visible retinal area among the Early Treatment Diabetic Retinopathy Study (ETDRS) seven-field, ultra-widefield (UWF)-Optos, and UWF-Clarus fundus imaging methods. METHODS: This was a prospective and clinic-based comparative study. All patients underwent three fundus examinations, and all images were graded using the ETDRS severity scale. We compared and analysed the agreement of DR severity and the relative visible retinal area among the three fundus examination methods, and the number and type of lesions outside the ETDRS seven-field (peripheral lesions) between the two UWF imaging methods. RESULTS: A total of 202 patients (386 eyes) were included. Weighted kappa for the agreement between ETDRS seven-field and blinded Optos images was 0.485; between ETDRS seven-field and blinded Clarus images, 0.924; and between blinded Optos and Clarus images, 0.461. Blinded Clarus showed excellent performance when a ETDRS scale was used for grading the images. The relative visible retinal area for ETDRS seven-field images was 195 ± 28 disc area (DA); single Optos images, 371 ± 69 DA; single Clarus images, 261 ± 65 DA; two-montage Clarus images, 462 ± 112 DA; and four-montage Clarus images, 598 ± 139 DA. The relative visible retinal area was statistically significant between any two of the imaging systems used. In total, 2015 and 4200 peripheral lesions were detected in single Optos and Clarus images, respectively (P < 0.001). These peripheral lesions on two UWF images suggested a more severe DR level in approximately 10% and 12% of eyes, respectively. CONCLUSION: UWF-Clarus fundus imaging offers a suitable assessment approach for DR severity; it could improve DR diagnosis and has the potential to replace ETDRS seven-field imaging after additional clinical trials.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/pathology , Prospective Studies , Photography/methods , Retina/diagnostic imaging , Retina/pathology , Fundus Oculi , Diabetes Mellitus/pathology
13.
BMC Ophthalmol ; 23(1): 114, 2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36949450

ABSTRACT

PURPOSE: Myopic scleral pit (MSP) is a rare physical sign of pathological myopia (PM). The aim of this study was to summarize the clinical characteristics of MSP and analyze its correlation with PM. METHODS: Eight cases with PM and MSP were enrolled in this study. Comprehensive ophthalmic examinations, including subjective refraction, slit-lamp biomicroscope, intraocular pressure, fundus photographs, A- and B-scan ultrasonography and spectral-domain optical coherence tomography, were performed. RESULTS: All the patients had a long history of PM with visual impairment, long axial length, and myopia-related fundus degeneration. Mean axial length was 31.48 ± 2.17 mm. Mean size of MSP was 0.69 ± 0.29 optic disc diameter (PD). Mean logMAR BCVA was 1.21 ± 0.88 logMAR. Spearman correlation analysis showed that the logMAR BCVA had no correlation with the size of pits (P = 0.34). Fundus examination revealed a focal pale concave located in the sclera exposed area of retinal choroid atrophy was found in all cases. OCT showed a deep scleral pit where the retinal choroid was thin or absent, without retinal sensory detachment or sensory defect. CONCLUSIONS: This study identified a rare scleral lesion in all eight individuals with PM, which was termed "myopic scleral pit". This phenomenon is different from focal choroidal excavation and posterior staphyloma.


Subject(s)
Myopia, Degenerative , Retinal Detachment , Scleral Diseases , Humans , Myopia, Degenerative/complications , Myopia, Degenerative/diagnosis , Myopia, Degenerative/pathology , Sclera/diagnostic imaging , Sclera/pathology , Visual Acuity , Scleral Diseases/diagnosis , Scleral Diseases/etiology , Scleral Diseases/pathology , Choroid/pathology , Tomography, Optical Coherence/methods , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retinal Detachment/pathology
14.
Eye (Lond) ; 37(4): 607-617, 2023 03.
Article in English | MEDLINE | ID: mdl-35915232

ABSTRACT

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.


Subject(s)
CRISPR-Cas Systems , Retinitis Pigmentosa , Humans , Gene Editing , Genetic Therapy , Retinitis Pigmentosa/genetics
15.
Gene Ther ; 30(1-2): 160-166, 2023 02.
Article in English | MEDLINE | ID: mdl-35794468

ABSTRACT

X-linked retinitis pigmentosa (XLRP) is the most severe form of Retinitis Pigmentosa (RP) and one of the leading causes of blindness in the world. Currently, there is no effective treatment for RP. In the present study, we recruited a XLRP family and identified a 4 bp deletion mutation (c. 2234_2237del) in RPGR ORF15 with Sanger sequencing, which was located in the exact same region as the missing XES (X chromosome exome sequencing) coverage. Then, we generated cell lines harboring the identified mutation and corrected it via enhanced prime editing system (ePE). Collectively, Sanger sequencing identified a pathogenic mutation in RPGR ORF15 for XLRP which was corrected with ePE. This study provides a valuable insight for genetic counseling of the afflicted family members and prenatal diagnosis, also paves a way for applying prime editing based gene therapy in those patients.


Subject(s)
Eye Proteins , Genetic Diseases, X-Linked , Retinitis Pigmentosa , Humans , East Asian People , Eye Proteins/genetics , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/therapy , Genetic Diseases, X-Linked/diagnosis , Mutation , Pedigree , Retinitis Pigmentosa/genetics , Retinitis Pigmentosa/therapy
16.
Photochem Photobiol ; 99(4): 1149-1156, 2023.
Article in English | MEDLINE | ID: mdl-36435980

ABSTRACT

UV-B-induced corneal damage remains a challenge in clinics, and it is needed to develop novel and effective medicines against UV-B induced photodamage. 3,4-Dihydropyrimidine-2(1H)-thione derivatives have shown many interesting biological activities, including antibacterial, anti-inflammatory, antioxidant, etc. In order to find a promising anticorneal photodamage agent, we designed and synthesized two novel sulfonated dihydropyrimidinthione derivatives to evaluate cytoprotective effect against UV-B-mediated photodamage. With simple structure, compound 6 possessed good water solubility, photostability and biocompatibility. We demonstrated that 6 exhibited significant cytoprotective effects against UV-B-mediated photodamage and the cell viability was up to 93% at 0.2 mg mL-1 . The corneal cells were highly sensitive to UV-B radiation, resulting in the release of inflammatory mediators and DNA damage, which were significantly reversed by 6. Moreover, compound 6 reduced Bax and cleaved Caspase-3 expressions to suppress UV-B mediated the intrinsic apoptosis pathway. Our findings suggest that 6 is a promising UV-B resistant agent with potential to be a promising drug candidate for the treatment of corneal photodamage.


Subject(s)
Corneal Injuries , Ultraviolet Rays , Humans , Apoptosis , Signal Transduction , Anti-Inflammatory Agents/pharmacology
17.
Anal Biochem ; 658: 114940, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36209895

ABSTRACT

This paper presents a novel clustered regularly interspaced short palindromic repeat (CRISPR)-associated HRCA technique (CART). During the entire detection process of CART, the target DNA is first specifically recognized and cleaved by a pair of Cas9/sgRNA complexes; then, the cleaved product is ligated into circular DNA as the template of HRCA, and the circular DNA is efficiently amplified by HRCA. Therefore, CART has the advantages of Cas9/sgRNA (single-base mismatch specificity) and HRCA (isothermal reaction temperature and high sensitivity). This technique has been verified by detecting various human papillomavirus (HPV) genes with numerous subtypes. In summary, this study provides a new and effective method for the detection of nucleic acids.


Subject(s)
DNA , Nucleic Acid Amplification Techniques , Humans , Nucleic Acid Amplification Techniques/methods , DNA/genetics , DNA, Circular/genetics , Papillomaviridae , CRISPR-Cas Systems/genetics
18.
Mol Ther ; 30(9): 2933-2941, 2022 09 07.
Article in English | MEDLINE | ID: mdl-35821638

ABSTRACT

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ∼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.


Subject(s)
Adenine , Gene Editing , CRISPR-Cas Systems , Humans , Mutation
19.
Langmuir ; 38(14): 4364-4370, 2022 04 12.
Article in English | MEDLINE | ID: mdl-35360902

ABSTRACT

Poor solubility, low cellular uptake, and poor cell selectivity are the main obstacles hampering the therapeutic potential and clinic application of macromolecules. To overcome these limitations, here we propose a chemical modification strategy of macromolecules based on enzyme-instructed self-assembly (EISA). By using protoporphyrin IX (PpIX) and its metal complex Zn-PpIX as the modification objects, we demonstrated that the integration of enzymatic transformation and molecular self-assembly of macromolecules successfully improved the solubility of macromolecules, enhancing their intracellular uptake selectively against cancer cells. The proposed strategy is potentially applicable as a general tool for the development of macromolecule-based nanomedicine.


Subject(s)
Antineoplastic Agents , Antineoplastic Agents/chemistry , Nanomedicine
20.
BMC Ophthalmol ; 22(1): 171, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35428283

ABSTRACT

BACKGROUND: To investigate the efficacy and safety of reversed scleral tunnel technique for repairing iridodialysis after blunt force trauma. METHODS: A total of 51 eyes of 51 patients with iridodialysis undergoing surgery were included in this study. Patients were divided into 2 groups: group A (the reversed scleral tunnel technique) and group B (the control group). Before the procedure and at 1, 3, and 6 months afterward, data on the patients' age, gender, treatments, diagnosis, mechanism of injury, best-corrected visual acuity (BCVA), intraocular pressure (IOP), degree of iridodialysis, lens status, concomitant ocular damage, number of sutures, complications, and follow-up time were collected and compared between the 2 groups. RESULTS: Iridodialysis was repaired and the pupil shape was restored to nearly round in all eyes. Standard phacoemulsification or lens removal was performed in all eyes. A final BCVA ≥20/60 was achieved in 13 eyes (48.1%) in Group A and 13 eyes (54.2%) in Group B. The IOP remained stable during the follow-up period in all eyes except 2 eyes (7.4%) in Group A and 3 eyes (12.5%) in Group B with angle recession. There were no statistically significant differences in BCVA and IOP between group A and group B. Intraoperatively, A significantly lower percentage of extensive subconjunctival hemorrhage occurred in Group A compared to Group B (1 eye versus 24 eyes, χ2 = 47.1, P = 0.00). Hyphema was observed in 2 eyes (7.4%) in Group A and 1 eye (4.2%) in Group B. Postoperatively, two eyes (7.4%) in Group A and 2 eyes (8.3%) in Group B developed retinal detachment. No other complications were noted during the follow-up period. CONCLUSIONS: The reversed scleral tunnel technique is a safe and effective approach for repairing iridodialysis after blunt force trauma with few complications, favorable cosmetic and visual outcomes.


Subject(s)
Iris Diseases , Phacoemulsification , Humans , Iris Diseases/etiology , Iris Diseases/surgery , Phacoemulsification/methods , Retrospective Studies , Sclera/surgery , Visual Acuity
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