Enfermedades raras: desentrañando las bases biológicas para encontrar futuras terapias / Rare diseases: unraveling the biological basis to find future therapies

Resumen Las enfermedades raras, caracterizadas por su baja prevalencia y alta complejidad, afectan a millones de personas globalmente. Los avances en tecnologías como la secuenciación masiva mejoran nuestra capacidad de diagnóstico, aunque el manejo terapéutico sigue sien do mayoritariamente sintomático o paliativo, con muy escasos tratamientos curativos aprobados. En el contexto de las enfermedades raras, especial mente los trastornos del neurodesarrollo de base ge nética, el desarrollo de terapias se enfrenta a múltiples retos, como la alta variabilidad fenotípica, los diversos mecanismos moleculares y biológicos subyacentes y las dificultades en la evaluación del neurodesarrollo tanto en la historia natural como en los ensayos clínicos. En la actualidad, estrategias como el reposicionamiento de fármacos, el desarrollo de biomarcadores y un enfoque multilateral en la búsqueda de soluciones amplían las posibilidades y ofrecen un escenario esperanzador. Este trabajo revisa diversas estrategias en el desarrollo de terapias, desde las terapias génicas y epigenéticas hasta la intervención en potenciales dianas biológicas.

Abstract Rare diseases are characterized by low prevalence and high complexity, affecting millions globally. Although technologies like massive sequencing improve diagnose, therapeutic options remain largely symptomatic or pal liative, with few curative treatments approved. In the context of rare diseases, especially genetic neurodevelopmental disorders, therapy development faces obstacles such as phenotypic variability, diverse molecular mechanisms, and complexities in assessing neurodevelopment in natural history and clinical trials. Current strategies include drug repositioning, biomarker development, and a multilateral approach in seeking solutions, offering hope. This work reviews various strat egies in developing therapies, from gene therapy and epigenetic therapies to identifying biological targets.

The Genetics of Primary Open Angle Glaucoma Interventions: Therapeutic Directions and Future Predictions

The “multifactorial chronic optic neuropathy” known as primary open angle glaucoma (POAG) is typified by a “progressive loss of retinal ganglion cells (RGC), structural damage to the retinal nerve fiber layer (RNFL) and optic nerve head (ONH), as well as abnormalities in the visual field.” High intraocular pressure (IOP), age, genetics, family history, race, etc. are the main risk factors. One of the pathological implications of POAG is “pressure-induced” ONH damage, which results in modifications to the expression of retinal genes. The ensuing fluid backup raises IOP, which damages optic nerve and results in POAG. Numerous susceptibility genes and environmental factors contribute to the “genetic heterogeneity” of POAG, according to genetic studies. “A set of twelve chromosomal loci, referred to as GLC1A through GLC1L, have been mapped for POAG. Three genes—myocilin (MYOC), optic neuropathy-inducing protein (Optineurin, OPTN)), and WD repeat domain 36 (WDR36)—have been identified as the GLC1A, GLC1E, and GLC1G”. A better understanding of the molecular genetic pathways and the pathological mechanisms involving the disease-causing genes, may help clarify the pathophysiology that leads to the disease and a targeted treatment. The role of genetics in POAG highlights the importance of genes in recent research advances, their future directions, applications, and therapy. The advent of modern genetic discoveries and future directions in vector engineering makes the cure for POAG possible. The paradigm shift in glaucoma treatment has moved from direct RGC and ONH therapy to targeting associated brain centers.

CRISPR/Cas9-mediated genome editing: from basic research to gene therapy

CRISPR/Cas9 mediated genome editing is one of the most significant molecular tools discovered to edit the desired genes. It has ushered in a new era of novel possibilities of gene therapy. CRISPR/Cas9 system was originally observed as a part of the adaptive immune system in bacteria. It later on was adapted to carry precise and targeted alterations to the DNA in human cells to be used for gene therapy to correct genetic disorders and treat various severe diseases associated with the genetic changes. Besides this, the CRISPR/Cas9 system has been employed in pharmacogenomics to develop new drugs based on the patient’s genes, in modifying the organisms for research and even for diagnostic purposes in developing CRISPR based COVID-9 test. The recent approval of a CRISPR/Cas9 cellular gene therapy by FDA named “Casgevy” to treat sickle cell anemia is a testimonial to the potentials of CRISPR/Cas9 system in developing innovative gene therapies. This review details the mechanisms of CRISPR/Cas9 gene editing and its utilization in the ongoing clinical trials in the treatment of not only the monogenic disorders like sickle cell disease, thalassemia, and genetic blindness but also in treating multi-factorial diseases like cancers, cardiac diseases, diabetes, autoimmune diseases, viral infections such as human immunodeficiency virus (HIV) etc. An attempt has also been made to discuss the various limitations, challenges and ethical frameworks encompassing CRISPR/Cas9 based gene therapy in clinical settings.

REGULATORY PERSPECTIVE FOR GENE THERAPY PRODUCTS IN THE USA, EU AND JAPAN AND FUTURE ASPECTS

Gene Therapy Products (GTPs) hold immense promise in revolutionizing medical treatments by altering genetic expressions to address various diseases. This study gives a summary of gene therapy products and their prospective uses, their historical development and several treatment options, as an in-depth exploration of the regulatory considerations for GTPs in the United States of America (USA), European Union (EU), and Japan, along with insights into future aspects of this field. A comprehensive discussion follows detailing the regulatory landscape and approval pathways in the USA, EU, and Japan. Programs that are exclusive to each area, such as PRIME (Priority Medicines) in the EU, USA's RMAT (Regenerative Medicines Advanced Therapy) designation and the Sakigake system in Japan are examined. Milestone meetings, approval requirements, and specific regulatory guidelines for GTPs in each region are also thoroughly covered. A list of approved GTPs and a glimpse into the future of the field. Anticipated trends include increasing investments, challenges related to production costs, expansion of manufacturing capabilities, and regulatory updates. The various regulatory strategies in each area and their efforts to balance patient access and safety will have a big impact on GTPs marketed in the future. Japan is well-positioned to maintain it’s as a global leader in regenerative medicine and cell treatments because of its favourable regulatory environment and government backing.

Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system

Abstract Introduction Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

Recent developments in gene therapy research in India

Inherited genetic disorders are progressive in nature and lead to organ dysfunction or death in severe cases. At present, there are no permanent treatment options for >95% of inherited disorders. Different modes of inheritance, type of gene(s) involved, and population-based variations add further complexity to finding suitable cures for approximately 400 million patients worldwide. Gene therapy is a very promising molecular technique for the treatment of rare genetic disorders. Gene therapy functions on the basis of restoration, replacement, inhibition, and, most recently, editing of gene(s) to rescue the disease phenotype. Recent reports show that increasing numbers of gene therapy clinical trials are using viral vectors (64.2%) when compared with non-viral vectors. Rapid development of efficient viral vector systems like the adeno-associated virus (AAV) and lentivirus has significantly contributed to this progress. Notably, AAV-mediated gene therapy has shown high potential for genetic disease treatment as evident from recent clinical trials for the eye (NCT00999609), blood (NCT00979238), and neuro-muscular systems (NCT02122952). Safety and efficacy are the two most critical features required for vector(s) to qualify for pre-clinical and clinical trial approval. The process of clinical-grade vector production, evaluation, and approvals for gene therapy products requires significant technological development, knowledge enhancement, and large financial investments. Additionally, trained manpower is required to meet the demands for constant technical innovation. These factors together contribute towards exorbitant prices for every dose of a gene therapy product and thus pose a challenge for the gene therapy field. The Indian subcontinent has traditionally lagged behind North America, Europe, Japan, and others in gene therapy clinical trials due to factors like inadequate industrial-scientific infrastructure, lack of accessible and organized patient databases, low financial investments, etc. However, over the last decade, increasing awareness of rare diseases, and international approvals of gene therapies such as Luxturna, Zolgensma, Hemgenix, etc., have spurred gene therapy development in India as well. In view of these advances, this article outlines gene therapy research, regulatory processes, and the launch of gene therapy clinical trials in India in the context of major developments worldwide. We briefly describe ongoing gene therapy research across Indian organizations and the nascent gene therapy product manufacturing. Further, we highlight the various initiatives from the medical and patient community to avail rehabilitation and gene therapy options. We briefly discuss the roles of regulatory agencies and guidelines for gene therapy clinical trials in India. We anticipate that this concise review will highlight the promise of gene therapy for the large population of rare disease patients in India.

Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context

Spinal muscular atrophy (SMA) is a neuromuscular, rare genetic disorder caused due to loss-of-function mutations in the survival motor neuron-1 (SMN1) gene, leading to deficiency of the SMN protein. The severity of the disease phenotype is inversely proportional to the copy number of another gene, SMN2, that differs from SMN1 by a few nucleotides. The current diagnostic methods for SMA include symptom-based diagnosis, biochemical methods like detection of serum creatine kinase, and molecular detection of disease-causing mutations using polymerase chain reaction (PCR), multiplex ligation-dependent probe amplification (MLPA), and exome or next-generation sequencing (NGS). Along with detection of the disease-causing mutation in the SMN1 gene, it is crucial to identify the copy number of the SMN2 gene, which is a disease modifier. Therapeutic options like gene therapy, antisense therapy, and small molecules are available for SMA, but, the costs are prohibitively high. This review discusses the prevalence, diagnosis, available therapeutic options for SMA, and their clinical trials in the Indian context, and highlights the need for measures to make indigenous diagnostic and therapeutic interventions.

Rare genetic diseases in India: Steps toward a nationwide mission program

Rare genetic diseases are rare by themselves with prevalence of 1 in 25,000, but collectively they are a significant cause of morbidity and mortality. Till date, collectively there are more than 9,000 rare diseases documented, which impose a devastating impact on patients, their families, and the healthcare system, including enormous societal burden. Obtaining a conclusive diagnosis for a patient with a rare genetic disease can be long and gruelling. For some patients it takes months or years to receive a definite diagnosis, and around 50% of the patients remain undiagnosed even with expert clinical and advanced high-end laboratory investigations. Owing to the large population and practice of consanguinity the Indian population is a pool of indigenous variants and unreported phenotypes or diseases. A mission program on pediatric rare diseases is an unparalleled initiative to study unique clinical conditions via the use of latest state-of-art technologies and with the combination of a mulit-omics approach. Our initiative will not only provide diagnosis to patients with rare disease but also build a platform for translational research for rare disease screening, management, and treatment.

Non-viral delivery of nucleic acid for treatment of rare diseases of the muscle

Rare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy (SMA), limb girdle muscular dystrophy, and so on. Due to the infrequent occurrence of these disorders, development of therapeutic approaches elicits less attention compared with other more prevalent diseases. However, in recent times, improved understanding of pathogenesis has led to greater advances in developing therapeutic options to treat such diseases. Exon skipping, gene augmentation, and gene editing have taken the spotlight in drug development for rare neuromuscular disorders. The recent innovation in targeting and repairing mutations with the advent of CRISPR technology has in fact opened new possibilities in the development of gene therapy approaches for these disorders. Although these treatments show satisfactory therapeutic effects, the susceptibility to degradation, instability, and toxicity limits their application. So, an appropriate delivery vector is required for the delivery of these cargoes. Viral vectors are considered potential delivery systems for gene therapy; however, the associated concurrent immunogenic response and other limitations have paved the way for the applications of other non-viral systems like lipids, polymers, cell-penetrating peptides (CPPs), and other organic and inorganic materials. This review will focus on non-viral vectors for the delivery of therapeutic cargoes in order to treat muscular dystrophies.

Progress in role of Niemann-Pick C1 protein in Ebola virus infection and its targeted drugs / 中国药理学与毒理学杂志

Ebola viruses belong to the Filoviridae family,which is highly contagious and likely to cause a variety of symptoms,including severe haemorrhagic fever in humans and primates,with a case fatality rate of up to 90%.Niemann-Pick C1(NPC1)protein is an important receptor expressed in the endosomal membrane of host cells during Ebola virus infection,and its interaction with the glycoprotein(GP)cleaved by cathepsin of Ebola virus is a key link in the viral infection host,mediating the fusion of the viral envelope and endosomal membrane before releasing the viral genome to the host cell.Recent years have seen some small molecule inhibitors and monoclonal antibody gene therapy drugs devel-oped by using NPC1 protein as a target of broad-spectrum anti-filovirus drugs.This article introduces the structure of NPC1 and its role in Ebola virus infection,and summarizes small molecule inhibitors,monoclonal antibody drugs and gene therapy drugs targeting NPC1.

Double investigation of gene therapy / 中国医学伦理学

From the biological point of view,genes are the key to being human.With the continuous advancement of human gene technology,gene therapy has become a frontier topic with great vitality and controversy in the field of life science:it has brought more hope for the cure of diseases to human beings,but it has also triggered many ethical debates.This paper sorts out the ethical questions faced by gene therapy,extracts the challenges faced by individual rights,social justice,natural order and so on,and responds one by one,which shows that the development of gene therapy does not violate these ethical values in principle.However,the occurrence of gene editing events has sounded the alarm for us:where should the implementation boundary of gene therapy be?Through the comparative analysis of the gene editing incident and the Berlin patient case,the article points out that the study of technical safety is the key to safe application of gene therapy in clinical applications.

Optimal diagnosis and treatment for renal allograft fibrosis / 器官移植

Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice / 临床耳鼻咽喉头颈外科杂志

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Overexpression of NRF1 alleviates mitochondrial and cognitive dysfunction in mice models of Alzheimer's disease / 安徽医科大学学报

Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P＜0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P＜0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P＜0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P＜0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.

Advances in the treatment of Wilson disease / 国际儿科学杂志

Wilson disease（WD）is an inherited disorder caused by mutations in the ATP7B gene.It is characterized by pathological accumulation of copper in the organs throughout the body，especially the liver and brain. This article reviews the latest progress of existing and emerging therapies. At present，the most commonly used treatment methods are oral chelators of copper and zinc agents. Liver transplantation can be used as a treatment for end-stage patients. However，these treatment methods have some shortcomings：many side effects of drugs，poor treatment effect，lifelong treatment，poor patient compliance and so on. At present，the choice of drugs is still in the exploratory stage，and there are no guidelines to specify which patients should receive which treatment. In addition，there are many emerging therapies in different experimental stages，such as new chelators of copper，targeted molecular therapy，gene therapy and cell transplantation. The old methods have many disadvantages and lack large controlled clinical trials，and emerging research is still in its infancy，which are urgent questions.

Current status of research on the diagnosis and specific treatment of glycogen storage disease type Ⅱ / 中华实用儿科临床杂志

Glycogen storage disease type Ⅱ (GSDⅡ) is a rare autosomal recessive disorder.Infant onset of GSDⅡ usually accompanies progressive cardiac hypertrophy and muscle weakness, and eventually dies of cardiopulmonary failure.GSDⅡ is mainly screened and diagnosed by enzymatic and genetic tests.Enzyme replacement therapy (ERT) is the only currently approved treatment of GSDⅡ, which can effectively improve the function of the affected organs and the survival.Gene therapy and substrate reduction therapy for GSDⅡ are also undergoing basic or clinical research.This review summarizes the current research status of the diagnosis and treatment of GSDⅡ at home and abroad, focusing on the influencing factors for the efficacy of specific treatment (especially ERT), dosing regimen, and ways to improve the efficacy.

Research status and application prospect of cytokine therapy for osteoarthritis / 中国组织工程研究

BACKGROUND:In cartilage degeneration in osteoarthritis,cytokines and signaling pathways that target chondrocytes play an important role. OBJECTIVE:To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years,such as the mechanism of action and treatment modalities,in order to provide a basis for future exploration of new therapeutic targets and modalities. METHODS:Literature search was conducted on CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases.Chinese search terms were"osteoarthritis,cytokines,signal pathway,chondrocyte,inflammation,treatment".Finally,60 papers were included for review. RESULTS AND CONCLUSION:(1)In current studies,it is believed that the specific mechanism of osteoarthritis is not clear,and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways,which is a complex process of action.Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot.(2)The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis,and more studies turn to gene therapy.(3)The therapeutic methods of transforming growth factor β,recombinant factors of Wnt signaling pathway,gene therapy and mesenchymal stem cells have obtained positive research results.However,basic and clinical studies on safety and efficacy are likely to be conducted in future studies.(4)At present,relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice,while recombinant factor,gene therapy and mesenchymal stem cell therapy are all in the research stage,among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration,and are worthy of expectation in the future.However,more clinical and basic studies are needed to verify its effectiveness and safety,explore its mechanism of action and scope of application,and set standards for its clinical use.

Overexpression of Sema3A promotes osteogenic differentiation of dental pulp stem cells and MC3T3-E1 / 中国组织工程研究

BACKGROUND:Sema3A is a power secretory osteoprotective factor.However,studies about Sema3A-modified dental pulp stem cells(Sema3A-DPSCs)are rare. OBJECTIVE:To explore the osteogenic differentiation ability of Sema3A-DPSCs and their regulatory effect on the osteogenic differentiation of the pre-osteoblast cell line MC3T3-E1. METHODS:First,Sema3A-DPSCs were constructed using a lentivirus infection system carrying the Sema3A gene.Control lentivirus-treated DPSCs(Vector-DPSCs)were used as controls.Sema3A-DPSCs or Vector-DPSCs were co-cultured with proosteoblast line MC3T3-E1 at the ratio of 1∶1 and 1∶3 for 24 hours.Finally,the Sema3A-DPSCs,Vector-DPSCs and their co-cultured cells with MC3T3-E1 were cultured for osteogenic induction and differentiation.Osteogenic gene expression was detected by alkaline phosphatase staining,alizarin red staining and real-time quantitative RT-PCR to evaluate osteogenic differentiation ability. RESULTS AND CONCLUSION:(1)Sema3A mRNA and protein expression levels in Sema3A-DPSCs were significantly up-regulated.The level of secreted Sema3A in cell supernatant was up-regulated.(2)Compared with the Vector-DPSCs,mRNA expressions of osteogenic genes alkaline phosphatase,Runt-related transcription factor 2,osteocalcin and Sp7 transcription factors in Sema3A-DPSCs were up-regulated;the activity of alkaline phosphatase was enhanced,and the formation of mineralized nodules increased.(3)There were no obvious differences in proliferation between Sema3A-DPSCs and Vector-DPSCs.(4)Compared with MC3T3-E1/Vector-DPSCs co-culture system,the expression of MC3T3-E1 osteogenic genes was up-regulated,and the total alkaline phosphatase activity was enhanced and more mineralized nodules were formed in the MC3T3-E1/Sema3A-DPSCs co-culture system.(5)The results suggest that overexpression of Sema3A can enhance the osteogenic differentiation of DPSCs.Overexpression of Sema3A in DPSCs can promote osteogenic differentiation of MC3T3-E1 in the DPSCs/MC3T3-E1 co-culture system.

Clinical application of subretinal injection / 眼科新进展

The subretinal space is a potential area between the retinal pigment epithelium layer and the photoreceptor layer.Subretinal injection is a way of drug administration to the subretinal space.Compared with intravitreal injection,subretinal injection allowed drugs to take more direct and effective action on retinal photoreceptor cells and retinal pigment epithelial cells.In recent years,thanks to advances in medical technology and surgical instrumentation subretinal injection realizes a gradually expanded clinical application,becoming an important drug delivery method for gene therapy and cell therapy of various fundus oculi diseases and playing an increasingly prominent role in vitreoretinal surgery.This article will explore the indications,techniques,potential risks,and complications of subretinal injection.

Recent advances in biological therapy of diabetic retinopathy / 眼科新进展

Diabetic retinopathy(DR)is one of the most common fundus vascular diseases and a leading cause of blindness in adults of working age.The occurrence and development of DR involves a variety of pathophysiologic mecha-nisms,including metabolic dysregulation,oxidative stress,inflammation,and neurovascular unit hypofunction.Conven-tional clinical treatments,such as anti-vascular endothelial growth factor drugs and retinal laser photocoagulation,have long treatment cycles and variable outcomes in some patients and sometimes require vitrectomy in the later stages of the disease.With the in-depth research on the molecular level of the pathogenesis of DR,a number of biological therapeutic modalities,such as targeted therapy,gene therapy,immunotherapy and cell therapy,have received more and more atten-tion from researchers.This review summarizes the biologic therapeutic modalities currently available for DR and outlines the benefits and limitations of these approaches with a view to informing researchers.