干细胞移植在视网膜神经节细胞损伤修复中的应用

进行性视网膜神经节细胞损伤在一些致盲性眼病中屡见不鲜。目前临床上缺乏有效的损伤修复方法,然而最近研究显示干细胞移植为受损视网膜神经节细胞的保护和替代治疗提供了新思路。本文将就干细胞移植为基础的研究进展进行综述。     

干细胞治疗青光眼的研究进展

青光眼是一类不可逆性视神经变性和视野缺损的疾病,青光眼导致视神经损伤的机制目前尚未明确,临床上对青光眼的治疗一直未取得良好的效果.干细胞具有自我增殖和分化的能力.近年来随着对干细胞研究的深入,人类利用干细胞治疗青光眼成为可能.青光眼干细胞移植分两大类:一是基于小梁网的干细胞替代治疗,另一类是视网膜神经节细胞的替代治疗.本文就干细胞治疗青光眼的研究进展进行综述.     

干细胞移植治疗视网膜变性疾病的研究进展

视网膜变性疾病是一类与遗传相关的变性疾病,导致患者渐进性视觉丢失,是主要的致盲性眼病之一,其共同病理基础是视网膜光感受器细胞的变性、坏死和凋亡,然而目前尚无有效的治疗方法。细胞移植治疗是目前实验研究治疗视网膜变性疾病的主要方法之一。近年研究表明将感光前体细胞或视网膜色素上皮细胞移植到视网膜下腔或玻璃体内,可以延缓宿主感光细胞的凋亡、替代凋亡的感光细胞、挽救残存的视觉功能和修复视网膜结构。细胞移植治疗的一个很重要的问题是移植细胞的来源问题,目前主要的移植细胞来源是视网膜祖／干细胞、胚胎干细胞和诱导多潜能干细胞等。本文就干细胞移植治疗视网膜变性疾病的研究进展进行综述。     

视网膜修复中干细胞的应用

视网膜疾病由于其不可逆转的致盲性而影响人类生存质量.随着对干细胞研究的深入,基于干细胞移植的细胞替代疗法为视网膜疾病的治疗开辟了新的途径.近年来眼组织来源的视网膜干细胞或祖细胞、非眼组织来源的间充质干细胞、造血干细胞、神经干细胞、胚胎干细胞以及诱导多能干细胞在视网膜损伤疾病中的应用取得了很多突破性进展,它们不仅可以被诱导分化为各种视网膜神经元细胞、胶质细胞,而且移植到体内可以整合到损伤视网膜,甚至可以发挥正常视网膜神经元细胞功能.     

干细胞移植治疗青光眼的研究进展

青光眼是以视网膜神经节细胞(retinal ganglion cells,RGC)丢失导致不可逆性视力减退和视野丧失为特征的退行性视神经病变。干细胞具有全能性和自我更新的特性,干细胞治疗已被证明可用于视网膜退行性疾病的治疗,有望成为青光眼视功能恢复的有效手段。干细胞根据来源可分为胚胎干细胞、诱导多能干细胞和成体干细胞,在青光眼治疗中的移植方式包括前房移植、玻璃体内移植、视网膜下和脉络膜上腔移植。干细胞治疗青光眼的途径主要包括修复受损小梁网以降低眼压,以及替代或修复受损伤的RGC。目前干细胞移植治疗青光眼主要存在操作安全性、致瘤性及免疫排斥等问题。通过提取间充质干细胞外泌体和细胞外囊泡的治疗方式可能是较好的解决途径之一。     

重组逆转录病毒pLXSN-脑源性神经营养因子在小鼠胚胎细胞中的表达

神经干细胞移植是近年来治疗视神经损伤疾病新的研究方向之一,然而如何能够让干细胞在眼内移植后定向分化为视网膜神经节细胞,一直是个难题.     

胚胎干细胞在眼科的研究进展

胚胎干细胞是一类具有自我更新和高度增殖能力的全能干细胞。自1998年人类胚胎干细胞在体外成功培养后,国内外学者进行了大量的研究,越来越多的研究显示将胚胎干细胞作为细胞供体进行角膜移植和视网膜移植,可能补充损伤细胞,重建眼表和恢复视网膜功能,给一些难治性眼表及视网膜疾病的治疗提供了新的途径。本文就胚胎干细胞移植在眼科的应用前景作一综述。     

玻璃体内细胞移植或细胞衍生物注入在视神经损伤中的作用

视网膜神经节细胞绝大部分位于神经节细胞层,可通过视神经通路将光感受器接收的视觉信息传递至高级视觉中枢,产生视觉。视网膜神经节细胞损伤和视神经轴突的中断,往往会导致视力下降甚至失明。近年来研究证实,玻璃体内细胞移植对损伤的视神经具有保护作用,为视神经损伤的修复治疗提供了新的方向。本文就玻璃体内细胞移植或细胞衍生物注入在视神经损伤中的作用展开综述。     

重组逆转录病毒脑源性神经营养因子在小鼠胚胎细胞中的表达

神经干细胞移植是近年来治疗视神经损伤疾病新的研究方向之一，然而如何能够让干细胞在眼内移植后定向分化为视网膜神经节细胞，一直是个难题。脑源性神经营养因子（BDNF）作为神经营养因子家族的重要成员之一，因其能够促进神经细胞生长分化、维持神经细胞正常功能、减缓神经元的损伤、并能够防止损伤后的细胞凋亡而日益受到重视。我们将重组的真核表达载体pLXSN—BDNF进行体外包装并检测了BDNF基因在细胞中的表达，对BDNF基因转染的神经干细胞眼内移植，探讨该基因在视神经保护中的作用奠定了基础。     

诱导多能干细胞在视网膜疾病研究中的应用

诱导多能干细胞(induced pluripotent stem cells,iPSCs)是成体细胞通过重编程而获得的一类具有胚胎干细胞相似特性和功能的细胞.近年来,iPSCs在再生医学和干细胞研究领域备受关注,尤其是患者特异源性iPSCs,来源方便、无免疫排斥和伦理学问题,同时还可以保留特定个体基因型,为再生医学以及细胞移植疗法提供了新的细胞来源.目前,iPSCs在视网膜疾病研究领域取得了长足的进步.本文主要对iPSCs向视网膜色素上皮细胞、感光细胞和神经节细胞的诱导分化及细胞移植研究、安全性评价等方面进行综述,探讨iPSCs在视网膜疾病研究中的应用和前景.     

Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies

Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Müller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Müller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Müller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Müller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Müller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Müller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Müller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases.     

干细胞对视神经损伤的修复作用

视网膜神经节细胞损伤或死亡往往会导致视功能不可逆性损害。目前尚无有效的治疗方法修复损伤的视神经，恢复受损的视功能。干细胞具有多向分化潜能，其在视神经保护及损伤修复中的作用日渐成为研究热点。本文旨在对干细胞在视神经损伤修复基础和临床研究方面的进展进行综述。     

Primary retinal ganglion cells for neuron replacement therapy

Optic nerve damage as a result of trauma, ischemia, glaucoma or other forms of optic neuropathy disease, leads to disconnection between the eye and brain and death of retinal ganglion cells (RGCs), causing permanent loss of vision. Therapeutic options for treating optic neuropathy are limited and represent a signiifcant unmet medical need. Development of a regenerative strategy for replacement of lost RGCs lies at the core of the future cell-based therapy for these conditions. Successful long-term restoration of visual function depends on the type of cells for transplantation. Primary RGCs of neonatal mice are now reported to have the potential for serving such a purpose.     

Current approaches and future prospects for stem cell rescue and regeneration of the retina and optic nerve

The 3 most common causes of visual impairment and legal blindness in developed countries (age-related macular degeneration, glaucoma, and diabetic retinopathy) share 1 end point: the loss of neural cells of the eye. Although recent treatment advances can slow down the progression of these conditions, many individuals still suffer irreversible loss of vision. Research is aimed at developing new treatment strategies to rescue damaged photoreceptors and retinal ganglion cells (RGC) and to replace lost cells by transplant. The neuroprotective and regenerative potential of stem and progenitor cells from a variety of sources has been explored in models of retinal disease and ganglion cell loss. Continuous intraocular delivery of neurotrophic factors via stem cells (SC) slows down photoreceptor cells and RGC loss in experimental models. Following intraocular transplantation, SC are capable of expressing proteins and of developing a morphology characteristic of photoreceptors or RGC. Recently, recovery of vision has been achieved for the first time in a rodent model of retinal dystrophy, using embryonic SC differentiated into photoreceptors prior to transplant. This indicates that clinically significant synapse formation and acquisition of the functional properties of retinal neurons, and restoration of vision, are distinct future possibilities.     

Retinal stem cell transplantation: Balancing safety and potential

Stem cell transplantation holds great promise as a potential treatment for currently incurable retinal degenerative diseases that cause poor vision and blindness. Recently, safety data have emerged from several Phase I/II clinical trials of retinal stem cell transplantation. These clinical trials, usually run in partnership with academic institutions, are based on sound preclinical studies and are focused on patient safety. However, reports of serious adverse events arising from cell therapy in other poorly regulated centers have now emerged in the lay and scientific press. While progress in stem cell research for blindness has been greeted with great enthusiasm by patients, scientists, doctors and industry alike, these adverse events have raised concerns about the safety of retinal stem cell transplantation and whether patients are truly protected from undue harm. The aim of this review is to summarize and appraise the safety of human retinal stem cell transplantation in the context of its potential to be developed into an effective treatment for retinal degenerative diseases.     

Short-wavelength automated perimetry: it's role in the clinic and for understanding ganglion cell function

Short-wavelength automated perimetry (SWAP) is a more sensitive test than standard achromatic perimetry for early loss of vision due to glaucoma and other ocular and neurological diseases. SWAP is also more successful for detecting changes in vision as glaucoma progresses. Results from various visual function-specific tests, including SWAP, suggest that there are individual differences in ocular hypertensive and glaucoma eyes in the subtype of ganglion cell first affected. However, the disease targets the same retinal area for all function-specific tests that show a deficit in a given individual. Psychophysical tests of vision are critical to understand glaucoma's effect on retinal ganglion cells, to verify the success or failure of treatment including new neuroprotective agents, and to determine the relationship of genetic markers for glaucoma to the presence and progress of the disease.     

间充质干细胞来源外泌体对视网膜新生血管影响的研究进展

视网膜新生血管形成是许多视网膜疾病的病理特征,例如早产儿视网膜病变和糖尿病视网膜病变,可导致严重的视力丧失甚至失明。抑制视网膜新生血管形成是治疗这些视网膜疾病的治疗策略。目前,已存在几种抑制视网膜新生血管形成的治疗策略,包括激光封闭、抑制血管内皮生长因子(VEGF)以及干细胞的移植等。随着干细胞研究的深入,发现干细胞治疗尽管潜力极大,但亦存在如移植细胞的低生存力,先天异质性等技术障碍,目前研究发现来源于间充质干细胞(MSCs)的外泌体具有与MSCs相似的功能,且尺寸小、易于通过生物膜,为细胞治疗提供了一种新思路,本文就外泌体对视网膜新生血管疾病的最新进展作一综述。