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Dawn of ocular gene therapy:implications for molecular diagnosis in retinal disease

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Science China(Life Sciences) 2013年第2期56卷 125-133页

作者： ZANEVELD Jacques WANG Feng WANG Xia CHEN Rui Human Genome Sequencing Center Department of Molecular and Human GeneticsBaylor College of Medicine

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for ra- re genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients＇ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation（s） underlying disease. In this review, we discuss the application of Next Generation Sequencing （NGS） to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases： Leber＇s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt＇s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinforrnatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine.

关键词： next-generation sequencing (NGS) retinal disease molecular diagnosis Leber's Congenital Amarosis (LCA) Retinitus Pigmentosa (RP) Stargardt disease APEX personal medicine

Game Theory-Based Dynamic Weighted Ensemble for retinal disease Classification

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Intelligent Automation & Soft Computing 2023年第2期35卷 1907-1921页

作者： Kanupriya Mittal V.Mary Anita Rajam Department of CSE CEGAnna UniversityChennai600025India

An automated retinal disease detection system has long been in exis-tence and it provides a safe,no-contact and cost-effective solution for detecting this *** paper presents a game theory-based dynamic weighted ensem-ble of a feature extraction-based machine learning model and a deep transfer learning model for automatic retinal disease *** feature extraction-based machine learning model uses Gaussian kernel-based fuzzy rough sets for reduction of features,and XGBoost classiﬁer for the classiﬁ*** transfer learning model uses VGG16 or ResNet50 or Inception-ResNet-v2.A novel ensemble classiﬁer based on the game theory approach is proposed for the fusion of the outputs of the transfer learning model and the XGBoost classiﬁer *** ensemble approach signiﬁcantly improves the accuracy of retinal disease pre-diction and results in an excellent performance when compared to the individual deep learning and feature-based models.

关键词： Game theory weighted ensemble fuzzy rough sets retinal disease

Stem cell therapy in retinal diseases

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Neural Regeneration Research 2023年第7期18卷 1478-1485页

作者： Audrey Voisin Amaury Pénaguin Afsaneh Gaillard Nicolas Leveziel Laboratoire de Neurosciences Expérimentales et Cliniques Universitéde PoitiersINSERM 1084PoitiersFrance Department of Ophthalmology CHU PoitiersPoitiersFrance Laboratoires Thea Clermont-FerrandFrance

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately *** intensive research in the field of retinal disorders,there is currently no curative *** therapeutic approaches such as cell-based replacement and gene therapies are currently in *** the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for *** the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell *** this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

关键词： age-related macular degeneration cell transplantation clinical trial retinal disease retinal dystrophy stem cell

Development of Photobiomodulation and its Application in retinal diseases

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Proceedings of Anticancer Research 2021年第5期5卷 15-18页

作者： Yizhe Wu Pu Chen Jingan Tong Shaanxi University of Chinese Medicine Xianyang 712046Shaanxi ProvinceChina Affiliated Hospital of Shaanxi University of Chinese Medicine Shaanxi Xianyang 712000Shaanxi ProvinceChina Department of Endocrinology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061Shaanxi ProvinceChina

Photobiomodulation(PBM)is a therap-eutic approach that utilizes low-energy laser or light to regulate biological *** mechanism is to promote cytochrome C oxidase(CCO)through low energy light,regulate the REDOX of mitochondria,and then regulate the biological functions of tissues and *** with traditional laser,it has a higher *** are a large number of mitochondria in retinal tissue,and studies have shown that PBM has a good protective and regulatory effect on the mitochondrial functions of retina and optic ***,PBM is clinically applied to treat age-related macular degeneration,diabetic retinopathy and retinitis pigmentosa and other retinal *** order to provide a new direction for the treatment of retinal diseases,this paper reviewed the main parameters,mechanisms and the research progress of PBM in the fundus indications.

关键词： Photobiomodulation Mechanism Cytochrome C oxidase Parameters retinal disease

Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

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Neural Regeneration Research 2015年第12期10卷 1976-1981页

作者： Hua Wang Benson Wui-Man Lau Ning-li Wang Si-ying Wang Qing-jun Lu Raymond Chuen-Chung Chang Kwok-fai So Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical University Beijing Ophthalmology & Visual Sciences Key Laboratory Department of Rehabilitation Science The Hong Kong Polytechnic University Department of Anatomy Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulam The State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Research Centre of Heart BrainHormone and Healthy AgingFaculty of MedicineThe University of Hong Kong Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulam GMH Institute of Central Nervous System Regeneration Jinan University

Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic ***,it remains unclear regarding the effects of Lycium barbarum polysaccharides,the main component of Lycium barbarum,on in vivo proliferation of adult ciliary body *** this study,adult rats were intragastrically administered low-and high-dose Lycium barbarum polysaccharides（1 and 10 mg/kg）for 35 days and those intragastrically administered phosphate buffered saline served as *** number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups,in particular low-dose Lycium barbarum polysaccharides group,was significantly greater than that in the phosphate buffered saline ***-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic *** findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype.

关键词： nerve regeneration traditional Chinese medicine Lycium barbarum polysaccharides Lycium barbarum (wolJberry) retinal disease neurogenesis adult neural regeneration

The role of gap junctions in cell death and neuromodulation in the retina

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Neural Regeneration Research 2021年第10期16卷 1911-1920页

作者： Gergely Szarka Marton Balogh Adam J.Tengolics Alma Ganczer Bela Volgyi Tamas Kovacs-Oller Janos Szentagothai Research Centre University of PecsPecsHungary retinal Electrical Synapses Research Group National Brain Research Program(NAP 2.0)Hungarian Academy of SciencesBudapestHungary Department of Experimental Zoology and Neurobiology University of PecsPecsHungary Medical School University of PecsPecsHungary

Vision altering diseases,such as glaucoma,diabetic retinopathy,age-related macular degeneration,myopia,retinal vascular disease,traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable *** junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells,thereby playing a crucial role in *** they are permeable for macromolecules,able to cross the cellular barriers,they show duality in illness as a cause and as a therapeutic *** this review,we take recent advancements in gap junction neuromodulation(pharmacological blockade,gene therapy,electrical and light stimulation)into account,to show the gap junction’s role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

关键词： age-related macular degeneration bystander effect connexin diabetic retinopathy gap junction glaucoma neuromodulation retina retinal disease vision

Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2022年第7期17卷 1596-1603页

作者： Hui-Jun Zhang Xiao-Bin Liu Xiong-Min Chen Qi-Hang Kong Yu-Sang Liu Kwok-Fai So Jian-Su Chen Ying Xu Xue-Song Mi Shi-Bo Tang Department of Ophthalmology the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology Guangzhou Panyu Central HospitalGuangzhouGuangdong ProvinceChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Laboratory of retinal Cell Biology Aier Eye InstituteChangshaHunan ProvinceChina Aier Academician Station ChangshaHunan ProvinceChina Key Laboratory of CNS Regeneration(Jinan University) Ministry of EducationGuangzhouGuangdong ProvinceChina CoInnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

Retinitis pigmentosa is a retinal disease characterized by photoreceptor *** is currently no effective treatment for retinitis *** a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains *** this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches *** at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle *** increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of ***,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 ***,lutein reduced the expression of glial fibrillary acidic protein in Müller glial *** results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory *** study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval ***-20181217-02)on December 17,2018.

关键词： anti-inflammation glial fibrillary acidic protein lutein microglia Pde6brd10(rd10)mouse photoreceptor reactive gliosis retinal degeneration retinal disease retinitis pigmentosa

Wharton's jelly mesenchymal stem cells differentiate into retinal progenitor cells

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Neural Regeneration Research 2013年第19期8卷 1783-1792页

作者： Ying Hu Jun Liang Hongping Cui Xinmei Wang Hua Rong Bin Shao Hao Cui Department of Ophthalmology First Affiliated Hospital Harbin Medical University Department of Ophthalmology Shanghai East Hospital Affiliated to Tongji University Department of Histology and Embryology Mudanjiang Medical University Department of Ophthalmology Fourth Affiliated Hospital Harbin Medical University Department of Head-Neck and Breast Tumor Mudanjiang Tumor Hospital

Human Wharton＇s jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton＇s jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton＇s jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.

关键词： neural regeneration stem cells Wharton's jelly mesenchymal stem cells microenvironment induc-tion reagent induction retinal progenitor cells nerve cells retinal disease grants-supported paper neuroregeneration

The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials

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International Journal of Ophthalmology(English edition) 2016年第6期9卷 914-919页

作者： Ye Tao Tao Chen Bei Liu Li-Qiang Wang Guang-Hua Peng Li-Min Qin Zhong-Jun Yan Yi-Fei Huang Department of Ophthalmology Ophthalmology & Visual Science Key Lab of PLAGeneral Hospital of Chinese PLA Department of Clinical Aerospace Medicine the Fourth Military Medical University Department of Neurosurgery and Institute for Functional Brain Disorders Tangdu Hospitalthe Fourth Military Medical University

Transcorneal electrical stimulation （TES） is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa （RP）, traumatic optic neuropathy, anterior ischemic optic neuropathy （AION）, and retinal artery occlusions （RAOs）. Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations y/a functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.

关键词： transcorneal electrical stimulation therapeutic strategy retinal disease optic neuropathy