用于外层视网膜病变的表层型人工视网膜技术

老年黄斑变性和色素性视网膜炎是两种主要外层视网膜变性疾病，也是致盲的主要眼病。对于这种光感受器受损的视网膜疾病，人工视网膜技术是一种非常有希望的治疗途径。现在的人工视网膜技术都是基于神经电刺激发展起来的。在过去的二十多年时间里，人工视网膜技术主要分为两大方向：外层型和表层型。两种人工视网膜技术各有优缺点。对于表层型人工视网膜，植入更为方便，并且可以利用玻璃腔的空间对植入物进行散热。本文首先从视网膜多层结构的信号转换和传递功能出发，简单的介绍了人工视网膜技术的概念；概括了表层型视网膜电刺激需要考虑的一些重要方面；最后总结了美国、德国和日本的研究者研究的几种表层型人工视网膜方案。可以肯定，随着各相关学科的发展，人工视网膜将在不久的将来得到广泛的应用。     

人工视网膜的研究进展

应用人工视网膜激活视网膜内层,将是治疗外层视网膜变性疾病的一种有希望的途径,近年来已在研发不同的新装置上付出了很大努力,现对3种类型的人工视网膜,即表面型人工视网膜,外层型人工视网膜及化学型人工视网膜的最新进展作一评述。     

视网膜下人工假体植入后视网膜变化的研究进展

视网膜下人工假体是目前关于视网膜色素变性和老年性黄斑变性等视网膜外层退行变性疾病研究中的一种新的治疗方法。它旨在利用植入的微电极器替代变性的光感受器细胞,经光-电信号转换,对视网膜内层残留的双极细胞和神经节细胞产生电刺激,进而通过正常的视路在大脑视皮质诱发视觉反应,从而达到恢复视力的目的。然而视网膜下假体植入后视网膜的结构、功能及蛋白表达等可发生一些变化,有学者还发现视网膜下假体植入后一段时间内视网膜的结构和功能得到改善,推测可能有保护作用的参与,但其来源尚不完全明了。本文主要就视网膜下人工假体植入后视网膜的变化作一综述。     

视网膜假体的研究进展

目前视网膜假体是所有视觉假体中研究最成熟、最广泛的一种,其研究目标是帮助失明患者恢复有用视力,尤其针对因视网膜色素变性和年龄相关性黄斑变性等致视力丧失者.依电刺激部位不同,视网膜假体分为视网膜上假体和视网膜下假体.前者通过玻璃体手术将微电极植入并固定于视网膜上;后者通过巩膜途径或玻璃体途径将微电极置于视网膜神经上皮层和视网膜色素上皮层之间.近年来对视网膜上假体的阵列电极、刺激电流等进行了改进;对视网膜下假体的芯片、供能方式等做了改进.有望为不可逆盲者提供帮助.     

变性性视网膜劈裂

变性性视网膜劈裂(degenerative retinoschisis)是视网膜劈裂中最多见的一种。随着临床研究的深入、检查手段的更新和手术技术的提高,对变性性视网膜劈裂的诊断及处理提出一些新的认识和方法。本文就这些方面作一综述。     

视网膜芯片的研究和应用进展

随着微电子技术的发展和电子耳蜗的广泛应用，人们试图通过人工视觉的方法治疗某些致盲性疾病。目前人工视觉的研究热点主要是通过视网膜表面或视网膜下芯片，替代视网膜色素变性等疾病中光感受器所丧失的功能。研究结果表明，电刺激视网膜可以诱发皮质电位。人工视觉所产生的效果，可以帮助患辨别方向和简单的图形轮廓，明显提高其生活质量。     

视网膜裂孔伴变性的临床特征和氪激光治疗

目的 探讨无症状和有症状视网膜裂孔、变性临床特征及氪激光治疗效果.方法 散瞳检查无症状视网膜裂孔伴变性58眼,有症状视网膜裂孔伴变性49眼.分析两组裂孔形态视网膜变性等相关临床特征,氪激光治疗效果.结果 无症状组平均年龄28岁,圆孔占81.03%、马蹄孔占18.97%,格子样变性44.83%、囊样变性17.24%、霜样变性37.93%,氪激光治疗有效达100%.有症状组平均年龄43.50岁,马蹄孔65.31%、圆孔34.69%,格子样变性67.25%、囊样变性22.45%、霜样变性10.20%,氪激光治疗有效达94.92%,,两组比较P<0.01.结论 无症状视网膜裂孔多见中青年、中高度近视患者,多数为圆孔,多不伴有视网膜脱离,格子样变性多见,其次霜样变性,氪激光治疗效果满意,能有效预防视网膜脱离.有症状视网膜裂孔多见老年人,多数为马蹄孔,格子样变性占首位,其次囊样变性,单纯视网膜裂孔氪激光治疗效果满意,伴玻璃体牵引明显的大裂孔疗效欠佳,需手术治疗.     

Nd：YAG激光后囊膜切开术后的视网膜脱离

人们普遍认为Ｎｄ：ＹＡＧ激光后囊膜切开增加了人工晶体眼、无晶体眼发生视网膜脱离的危险性。发生率０．０８％－４．７％，１９８８年以前≤２％，１９８８以后有所增加。轴性授视，视网膜格子样变性，对侧眼视网膜脱离史，年轻，男性等是发生视网膜脱离的危险因素，视网膜脱离的临床特点与人工晶体眼视网膜脱离相似，但发生机理沿不明了。     

有裂孔的视网膜变性的临床特征和氩激光治疗

目的 探讨有裂孔的视网膜变性的临床特征和氩激光治疗效果。 方法 回顾性分析本院210例224只眼相应视网膜变性的氩激光治疗资料，并与同期尚无裂孔的视网膜变性氩激光治疗对照。 结果 有裂孔的视网膜变性患者，小于60岁者89.7%，男性53.3%，女性46.7%，格子样变性65.6%，变性范围≤1个象限者87.5%，卵圆形裂孔60.7%，伴有局限性视网膜浅脱离者23.7%。与尚无裂孔的视网膜变性患者相比，≥35岁、囊样变性、视网膜纵向小皱襞、有自觉症状的患眼构成比明显偏高，而氩激光视网膜脱离预防性治疗对已出现局限性孔源性视网膜脱离的视网膜变性患者疗效明显偏低(P<0.01)。 结论 有裂孔的视网膜变性常见于青壮年，多数患者为1个象限内的格子样变性；裂孔多数为卵圆形，多不伴有视网膜脱离；裂孔没有明显的性别差异，多数没有自觉症状。不伴有视网膜脱离的视网膜单纯性裂孔的视网膜变性，氩激光视网膜脱离预防性治疗可获得满意疗效。 (中华眼底病杂志, 2006, 22: 39-41)     

视网膜芯片的研究和应用进展

随着微电子技术的发展和电子耳蜗的广泛应用,人们试图通过人工视觉的方法治疗某些致盲性疾病。目前人工视觉的研究热点主要是通过视网膜表面或视网膜下芯片,替代视网膜色素变性等疾病中光感受器所丧失的功能。研究结果表明,电刺激视网膜可以诱发皮质电位。人工视觉所产生的效果,可以帮助患者辨别方向和简单的图形轮廓,明显提高其生活质量。     

The bionic eye (electronic visual prosthesis): A review

The concept of a visual prosthesis for the blind or partially sighted is not a new one. Indeed, for more than three decades this technology based treatment for blindness has appeared imminent. Despite the concerted efforts of numerous physicians, scientists and engineers, the successful application of a useful visual prosthesis remains elusive. The present review will endeavour to describe past efforts, investigate the present state of the art and indicate the obstacles that must be overcome in order to bring an electronic visual prosthesis to fruition.     

A review of in vivo animal studies in retinal prosthesis research

Background  The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. Methods  A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. Results  We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). Conclusion  The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field. The authors have no commercial interest in any device or product mentioned.     

Spatiotemporal aspects of pulsed electrical stimuli on the responses of rabbit retinal ganglion cells

Implanted intraocular microelectrode arrays are being used to provide sight to individuals who are blind due to photoreceptor degeneration. It is envisioned that this retinal prosthesis will create the illusion of motion by stimulating focal areas of the retina in a sequential fashion through neighboring electrodes, much like the rapid succession of still images in movies and computer animation gives rise to apparent motion. Using a high-density microelectrode array, we examined the extracellularly recorded responses of rabbit retinal ganglion cells to a bar-shaped electrode array that was stepped at 50 μm increments at different rates across the retina and compared these respons2es to the responses generated to a similarly shaped light stimulus that was stepped across the retina. When the retina was stimulated at 1 step/s, retinal ganglion cells gave robust bursts of action potentials to both the electrode array and the light stimulus. The responses to the ‘moving’ electrode array decreased progressively with increasing stepping frequency. At 16 steps/s (highest frequency tested), the number of spikes per sweep and the number of bursts per sweep were reduced 75% and 67% respectively. In contrast, when the retina was stimulated at 16 steps/s with the ‘moving’ light stimulus, the number of spikes per sweep and the number of bursts per sweep were reduced only 43% and 25% respectively. These findings suggest that simple translation of object motion to sequential stimulation through neighboring electrodes may not be the best way to convey the perception of object motion in a patient with a retinal prosthesis.     

Feasibility of extraocular stimulation for a retinal prosthesis

BACKGROUND: We present a new approach to developing a retinal prosthesis for blind patients based on extraocular stimulation of the eye with disc electrodes. METHODS: Experiments to assess the feasibility of using extraocular stimulation in a retinal prosthesis were carried out in anaesthetised adult cats (n=6). A craniotomy and lateral orbital dissection were performed. Ball or disc electrodes were placed on the posterior scleral surface of the eye after incision of the periorbita. Cortical potentials evoked by electrical stimulation with these electrodes were recorded at the primary visual cortex. The viability of adapting the Nucleus 24 auditory brainstem implant (ABI) as an extraocular retinal prosthesis was also investigated. RESULTS: Electrodes placed on the exterior of the eye could reliably evoke visual cortex responses for a variety of configurations. Threshold currents for eliciting an evoked response were lower than 100 microA with single pulses. Strength-duration curves and cortical activation maps were obtained for different stimulus paradigms. It was possible to excite the retina to evoke a cortical response using the electrodes and stimulus capabilities in a standard Nucleus 24 ABI. INTERPRETATION: It is possible to electrically stimulate the retina with electrodes placed in an extraocular location. Threshold currents required to elicit a response were low, and comparable to epiretinal implants. Prototype electrodes, and a potential implant, were found to be effective at retinal stimulation.     

Studies on pathogenesis and gene therapy of red-green color blindness北大核心CSCD

Red-green color blindness is the most common form of colour blindness. Traditional treatment options such as tinted lenses do not cure color blindness completely. With the rapid development of gene diagnostic and managing technology, gene therapy has been applied to inherited retinal diseases widely. The genetic treatment of Leber congenital amaurosis has entered clinical trail and shown the remarkable success in safety and efficacy. In recent years, gene therapy has finally reached a milestone to convert adult male squirrel monkeys with red-green color blindness to trichromats. It heralds the bright prospects of gene therapy applied in human red green color blindness. This article briefly reviewed the recent preclinical research achievements of pathogenesis and gene therapy for red-green color blindnes. Copyright © 2018 by the Chinese Medical Association.     

Visual–tactile shape perception in the visually restored with artificial vision

Retinal prostheses partially restore vision to late blind patients with retinitis pigmentosa through electrical stimulation of still-viable retinal ganglion cells. We investigated whether the late blind can perform visual–tactile shape matching following the partial restoration of vision via retinal prostheses after decades of blindness.We tested for visual–visual, tactile–tactile, and visual–tactile two-dimensional shape matching with six Argus II retinal prosthesis patients, ten sighted controls, and eight sighted controls with simulated ultra-low vision. In the Argus II patients, the visual–visual shape matching performance was significantly greater than chance. Although the visual–tactile shape matching performance of the Argus II patients was not significantly greater than chance, it was significantly higher with longer duration of prosthesis use. The sighted controls using natural vision and the sighted controls with simulated ultra-low vision both performed the visual–visual and visual–tactile shape matching tasks significantly more accurately than the Argus II patients. The tactile–tactile matching was not significantly different between the Argus II patients and sighted controls with or without simulated ultra-low vision.These results show that experienced retinal prosthesis patients can match shapes across the senses and integrate artificial vision with somatosensation. The correlation of retinal prosthesis patients’ crossmodal shape matching performance with the duration of device use supports the value of experience to crossmodal shape learning. These crossmodal shape matching results in Argus II patients are the first step toward understanding crossmodal perception after artificial visual restoration.     

Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish

Adult zebrafish generate new neurons in the brain and retina throughout life. Growth-related neurogenesis allows a vigorous regenerative response to damage, and fish can regenerate retinal neurons, including photoreceptors, and restore functional vision following photic, chemical, or mechanical destruction of the retina. Müller glial cells in fish function as radial-glial-like neural stem cells. During adult growth, Müller glial nuclei undergo sporadic, asymmetric, self-renewing mitotic divisions in the inner nuclear layer to generate a rod progenitor that migrates along the radial fiber of the Müller glia into the outer nuclear layer, proliferates, and differentiates exclusively into rod photoreceptors. When retinal neurons are destroyed, Müller glia in the immediate vicinity of the damage partially and transiently dedifferentiate, re-express retinal progenitor and stem cell markers, re-enter the cell cycle, undergo interkinetic nuclear migration (characteristic of neuroepithelial cells), and divide once in an asymmetric, self-renewing division to generate a retinal progenitor. This daughter cell proliferates rapidly to form a compact neurogenic cluster surrounding the Müller glia; these multipotent retinal progenitors then migrate along the radial fiber to the appropriate lamina to replace missing retinal neurons. Some aspects of the injury-response in fish Müller glia resemble gliosis as observed in mammals, and mammalian Müller glia exhibit some neurogenic properties, indicative of a latent ability to regenerate retinal neurons. Understanding the specific properties of fish Müller glia that facilitate their robust capacity to generate retinal neurons will inform and inspire new clinical approaches for treating blindness and visual loss with regenerative medicine.     

Recapitulating developmental mechanisms for retinal regeneration

Degeneration of specific retinal neurons in diseases like glaucoma, age-related macular degeneration, and retinitis pigmentosa is the leading cause of irreversible blindness. Currently, there is no therapy to modify the disease-associated degenerative changes. With the advancement in our knowledge about the mechanisms that regulate the development of the vertebrate retina, the approach to treat blinding diseases through regenerative medicine appears a near possibility. Recapitulation of developmental mechanisms is critical for reproducibly generating cells in either 2D or 3D culture of pluripotent stem cells for retinal repair and disease modeling. It is the key for unlocking the neurogenic potential of Müller glia in the adult retina for therapeutic regeneration. Here, we examine the current status and potential of the regenerative medicine approach for the retina in the backdrop of developmental mechanisms.