经角膜电刺激在视网膜疾病治疗中的研究进展

近年来,眼部电流刺激(electrical stimulation,ES)在不同方向的研究中逐渐揭示了其在多种视网膜疾病中的潜在治疗价值。其中,经角膜电刺激(transcorneal electrical stimulation,TES)作为一种非侵入性的治疗方法,能对视网膜、视神经、眼底血管及其相关结构产生积极的影响。TES能够改善视力,在保护感光细胞和减缓疾病进展方面显示出积极效果,提高患者的生存质量,还能够在不损伤眼球的情况下调节大脑中的神经元活动,为视网膜疾病的治疗提供一种新的选择。该文对近年来TES在视网膜色素变性(retinitis pigmentosa,RP)、年龄相关性黄斑变性(age-related macular degeneration,AMD)、视网膜血管病、青光眼以及视神经病变等疾病中的应用研究进行了综述。研究发现,TES治疗是一种安全且无需手术的辅助治疗工具,具有广泛的应用前景。该文旨在为临床医师提供一个全面的TES研究概述,并深入探讨其在眼科学领域的潜在应用价值。然而,TES治疗的具体机制仍需进一步探讨,以便更好地应用于临床实践。同时,未来研究还应关注TE...     

光感受器移植在视网膜退行性疾病中的应用研究进展

视网膜退行性疾病是影响人类视力的主要疾病,使人感光细胞受损,损害人的视力。而且哺乳动物的视网膜没有再生能力,一旦患病会严重影响人们的正常生活。目前尚未有明确的预防和减缓该类疾病的方法,但移植光感受器以补充视网膜中受损的感光细胞可以治疗视网膜疾病。本文将讨论光感受器移植方法在视网膜退行性疾病中恢复视力的现状和移植技术。     

视网膜类器官治疗视网膜退行性疾病的研究进展

视网膜退行性疾病是导致视力受损与失明的重要原因。目前,对于感光细胞大量丧失的疾病晚期阶段尚无有效的治疗方案。近年来,大量研究提供了感光细胞的移植替代治疗的新思路,而视网膜3D培养技术产生的视网膜类器官能够在体外产生移植所需的感光细胞及组织,为视网膜退行性疾病的移植替代治疗奠定了基础。本文通过综述视网膜3D培养技术以及感光细胞移植的发展,着重阐述视网膜类器官在视网膜退行性疾病移植替代治疗中的现有运用策略以及局限性,以期为视网膜3D培养技术在感光细胞替代治疗中的优化提供理论参考。     

神经炎症在视网膜退行性疾病中作用的研究进展

视网膜退行性疾病(RD)是全球范围内不可逆性致盲眼病的主要原因,其特征是视网膜神经元的进行性退化,造成视觉功能严重受损。目前针对该病以对症治疗为主,而对于视网膜神经元的保护及视觉重构的效果有限。近年来随着对RD发病机制研究的深入,发现神经胶质细胞迁移、募集和激活及细胞因子产生是RD中视网膜细胞进行性凋亡的关键因素,因此神经炎症有望成为预防和治疗此病的新途径。本文就神经炎症在RD的基础研究和临床治疗两方面进行综述。     

骨髓间充质干细胞神经保护作用在视网膜疾病治疗中的研究进展

骨髓间充质干细胞（ MSCs）是来源于骨髓的具有多种神经营养因子分泌功能的多能干细胞,被广泛应用于组织、细胞的修复或替代研究中。有研究表明MSCs分泌的多种神经营养因子,有助于提高病理状态下神经细胞的存活能力。因此,MSCs的神经保护功能也逐渐被应用于视网膜疾病的研究中。视网膜细胞对损伤非常敏感且自我修复能力较差,利用MSCs的这一功能可为病变视网膜的治疗带来新的希望。本文就MSCs的神经营养因子分泌功能及其对视网膜细胞产生的神经保护作用和在不同视网膜疾病中的研究应用进展等方面进行综述,并展望其在视网膜疾病治疗中的应用前景。     

神经营养素在视网膜及视神经疾病方面的研究

神经营养素是一类结构和功能相近的多肽类家族,广泛分布于人体各种组织细胞中,有着重要的生物学特性,在临床已广泛应用,在眼科方面也有研究。对神经营养素及其受体在视网膜组织的分布作了描述和分析,并对神经营养素在视网膜及神经疾病方面的基础及临床研究作了综述。     

眼的神经生物学研究进展

视觉器官特别是视网膜、视路以及分布于视器各组织中的支配神经是人类神经系统的一个重要组成部分。从眼的神经解剖角度看 ,眼部神经竟有 12对颅神经中的 6对。此外 ,眼组织中还有植物神经 (交感神经、副交感神经 )纤维分布。可见视觉器官中的神经种类多、数量大 ,神经支配极为复杂 ,且与中枢神经有着密切的联系。眼的神经生物学或称视觉神经生物学范畴广泛 ,包括使用各种方法、各种学科技术对眼的神经系统的形态结构和功能代谢等各个方面进行研究。近十几年来在视觉器官神经组织的突轴学、轴浆流动与运输以及神经保护与再生方面已取得丰硕…     

电、磁刺激在耳鸣治疗中的应用进展

电、磁刺激可以通过改变神经元兴奋性进而调节大脑内特定区域的功能,被广泛应用于神经系统疾病的诊断和治疗。近年来,电、磁刺激应用于治疗耳鸣也取得了很大的进展。本文简述电、磁刺激疗法的基本原理,并对其应用于耳鸣治疗的相关研究进展进行综述。     

视网膜视神经挫伤电生理改变500例分析

目的　探讨眼球挫伤后不同受伤部位、程度与视网膜电图 (ERG)、视诱发电位 (VEP)敏感度之间的关系。方法　 VEP使用黑白棋盘格反转刺激 12 8次 (P- VEP) ,记录结果。 ERG则采用单次闪光暗适应 ERG(F-ERG) ,统一记录条件 ,分别记录。结果　轻度视网膜损伤就可表现为 F- ERG的 b波下降 ,较严重病例才表现为 P- VEP异常。不同组病例 F- ERG和 P- VEP改变与眼球挫伤部位、程度有相关性。结论　视网膜损伤多表现为F- ERG改变 ,其中以 b波降低最敏感。 P- VEP对于轻度视神经损伤就有较高敏感性 ,严重病例 P- VEP可熄灭     

神经干细胞移植术治疗视网膜退行性疾病

各种退行性视网膜病变缺乏常规的治疗方法,通过干细胞移植,使其整合入视网膜各层并且分化为目标细胞,以重建视网膜功能,给不可逆性盲眼患者带来了曙光。近年来视网膜干细胞移植的试验性研究取得了重大的进展。现就视网膜神经干细胞移植的供体材料来源、诱导分化及影响因素和试验研究的最新进展作一综述。     

Pathology of damaging electrical stimulation in the retina

The goal of this study was to examine the characteristics of electrically induced retinal damage. A retinal prosthesis must be both effective and safe, but most research related to electrical stimulation of the retina has involved measures of efficacy (for example, stimulus threshold), while relatively little research has investigated the safety of electrical stimulation. In this study, a single platinum microelectrode was inserted into the vitreous cavity of normally-sighted adult Long Evans pigmented rats. In one group of animals, no contact was made between the electrode and the retina and current pulses of 0.05 (n=3) and 0.2 (n=6) microC/phase were applied. In a second group, visible contact (slight dimpling of the retina) was made between the electrode and the retina and current pulses of 0.09 (n=4) microC/phase were applied. In both cases, stimulus pulses (biphasic, cathodic first, 1 ms/phase) were applied for 1 h at 100 Hz. Also, control experiments were run with no electrical stimulation with retina contact (n=4) and with no retinal contact (n=3). After stimulation, the animal was survived for 2 weeks with ocular photography and electroretinography (ERG) to document changes. During the follow-up period, retinal changes were observed only when the electrode contacted the retina, with or without electrical stimulation. No difference was noted in ERG amplitude or latency comparing the test eye to the stimulated eye. Histological analysis was performed after sacrifice at 2 weeks. A semi-quantitative method for grading 18 features of retina/RPE/choroidal appearance was established and integer grades applied to both test and control eyes. Using this method and comparing the most severely affected area (highest grade), significant differences (p<0.05) were noted between experiments with retinal contact and without retinal contact in all features except inner nuclear layer thickness. No difference was noted within a group based on the intensity of electrical stimulus applied. The size of the affected area was significantly larger with both retinal contact and electrical stimulation compared to with retinal contact alone. We conclude that mechanical pressure alone and mechanical pressure with excessive electrical stimulation causes damage to the retina but that electrical stimulation coupled with mechanical pressure increases the area of the damage.     

Acute electrical stimulation of the human retina with an epiretinal electrode array

Purpose: To determine the threshold charges needed for eliciting visual perceptions through acute electrical stimulation of the human retina in patients suffering from retinitis pigmentosa, using an epiretinal microelectrode array. Methods: In a multicentre study, 20 patients (average age 55 years) with visual acuities ranging from 4/200 to no light perception were included. The stimulation procedure was performed during a pars plana vitrectomy, for a maximum of 45 min, by using a microcontact film with IrO_x electrodes connected by cable to a current generator. After repeated stimulation and threshold charge determination, the microelectrode array was removed. Results: Nineteen of 20 patients stated in the postoperative interviews that they experienced one or more visual perceptions with close time correlation to single stimulation events. Minimum threshold charges needed to generate visual perceptions could be measured and verified in 15 patients. The charge level ranged from 20 to 768 nC with single or multiple electrodes. One patient suffered a retinal detachment during the procedure; this patient’s retina was successfully reattached. There were no further adverse reactions observed during the 3‐month follow‐up. Conclusion: Acute epiretinal stimulation of the human retina, using a microelectrode array, can elicit visual perceptions in blind patients with retinitis pigmentosa.     

干细胞移植治疗视网膜和视神经变性疾病的现状和进展

不可逆性的视网膜和视神经退行性变会导致视功能严重损伤甚至致盲.近年来,干细胞移植治疗视网膜和视神经损伤的研究进展为组织的修复和再生带来了希望.干细胞既可以用于细胞替代治疗,也可以通过分泌细胞因子发挥神经营养保护作用.胚胎干细胞、间充质干细胞、诱导多能干细胞和Müller细胞等各种来源的干细胞都极具发展前景,为眼科此类难治性疾病提供了丰富的资源.     

Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina

AIMS: To demonstrate the quantitative distribution of mitochondrial enzymes within the human optic nerve and retina in relation to the pathogenesis of ophthalmic disease. METHODS: Enucleations were performed at the time of multiple organ donation and the optic nerve and peripapillary retina immediately excised en bloc and frozen. Reactivities of the mitochondrial enzymes cytochrome c oxidase and succinate dehydrogenase were demonstrated in serial cryostat sections using specific histochemical assays. RESULTS: In the optic nerve the unmyelinated prelaminar and laminar regions were rich in both cytochrome c oxidase and succinate dehydrogenase. Myelination of fibres as they exited the lamina cribrosa was associated with an abrupt reduction in enzyme activity. Within the retina, high levels of enzyme activity were found localised within the retinal ganglion cells and nerve fibre layer, the outer plexiform layer, inner segments of photoreceptors, and the retinal pigment epithelium. CONCLUSIONS: Mitochondrial enzyme activity is preserved in human optic nerve and retina retrieved at the time of multiple organ donation. The distribution of enzyme activity within the eye has implications for the understanding of the pattern of ophthalmic involvement seen in mitochondrial diseases and the site of ganglion cell dysfunction in those patients with optic nerve involvement.     

神经生长因子及其受体与视神经视网膜疾病的研究进展

目前关于神经生长因子在视网膜视神经疾病中的作用研究很多 ,但观点很不一致。本文着重论述神经生长因子及其受体在视觉系统的分布、视神经损伤、缺血性视网膜疾病、视网膜变性疾病及增生性玻璃体视网膜疾病中的作用。     

Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats

Purpose  To investigate whether electrical stimulation promoted axonal regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) crush in adult rats. Methods  Transcorneal electrical stimulation (TES), which stimulates the retina with current from a corneal contact lens electrode, was used to stimulate the eye. TES was applied for 1 h immediately after ON crush. Axonal regeneration was determined by anterograde labeling of RGC axons. To examine whether the axonal regeneration was mediated by insulin-like growth factor 1 (IGF-1) receptors, an IGF-1 receptor antagonist, JB3, was injected intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effects of TES. To test the survival-promoting effects of TES applied daily, the mean density of retrogradely labeled RGCs was determined on day 12 after ON crush. Results  Compared with sham stimulation, the mean number of regenerating axons significantly increased at 250 μm distal from the lesion and increased IGF-1 immunoreactivity was observed in retinas treated daily with TES. Preinjection of an IGF-1 receptor antagonist significantly blocked axonal regeneration by TES applied daily. TES applied daily also markedly enhanced the survival of RGCs 12 days after ON crush. Conclusion  TES applied daily promotes both axonal regeneration and survival of RGCs after ON crush.     

Effect of long-term weightlessness on retina and optic nerve in tail-suspension rats

AIM: To evaluate the effect of long-term weightlessness on retina and optic nerve in tail-suspension (TS) rats. METHODS: A stimulated weightlessness model was established by suspending rats’ tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells (RGCs) was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential (VEP) and oscillatory potentials (Ops). RESULTS: The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23±3.92 (vs 37.43±4.13, P=0.0145), the RGCs density was 1645±46 cells/mm2 (vs 1867±54 cells/mm2 P=0.0000), the incidence rate of retinal cells apoptosis was 5.38%±0.53% (vs 4.75%±0.54%, P=0.0238), the amplitude of VEP-P100 was 15.43±2.14 µV (vs 17.67±2.17 µV, P=0.0424), the latency of VEP-P100 was 69.05±5.34ms (vs 62.43±4.87ms P=0.0143) and the sum amplitude of Ops was 81.05±8.34 µV (vs 91.67±10.21 µV, P=0.0280) in TS group and the control group, respectively. CONCLUSION: Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats.     

Neuroprotective effect of transcorneal electrical stimulation on ischemic damage in the rat retina

Some previous studies have showed that transcorneal electrical stimulation (TES) could protect retinal neurons in certain rodent models. However, it is not yet clear whether TES could also definitely protect retinal neurons against ischemic insults. In the present study, we hypothesized that TES had such a neuroprotective effect and further investigated its underlying mechanism. Adult female Sprague–Dawley (SD) rats received TES treatment every other day after ocular ischemia was induced by elevating the intraocular pressure to 120 mmHg for 60 min. Retinal ganglion cells (RGCs) were labeled retrogradely 7 days before ischemia and were counted 7 and 14 days later. At the same time points, retinal function was assessed by scotopic electroretinography (ERG), combined with retinal histological analysis. The glutamine synthetase (GS) immunoreactivity was compared between ischemic retinas with TES and those with sham stimulation under identical confocal laser microscope conditions. The immunohistochemical indications were confirmed by Western blot analysis. Higher mean density of RGCs was quantified in TES treated retinas compared to retinas with sham stimulation on days 7 and 14 after ischemia. Similarly, histological analysis showed that TES better preserved the mean thickness of separate retinal layers. ERG studies indicated that by undergoing TES treatment, the b-wave amplitude was also significantly preserved on day 7 after ischemia and recovered robustly on day 14. Immunohistochemical and Western blot analysis both revealed that GS levels remarkably increased after TES and lasted for at least 7 days. Our results indicate that TES can protect retinal neurons against ischemic insults, probably related to increasing levels of GS localized in Müller cells. These findings suggest a new approach for potential clinical application to ocular ischemic diseases.     

Optimal parameters of transcorneal electrical stimulation (TES) to be neuroprotective of axotomized RGCs in adult rats

We previously showed that transcorneal electrical stimulation (TES) promoted the survival of axotomized retinal ganglion cells (RGCs) of rats. However the relationship between the parameters of TES and the neuroprotective effect of TES on axotomized RGCs was unclear. In the present study, we determined whether the neuroprotective effect of TES is affected by the parameters of TES. Adult male Wistar rats received TES just after transection of the left optic nerve (ON). The pulse duration, current intensity, frequency, waveform, and numbers of sessions of the TES were changed systematically. The alterations of the retina were examined histologically seven days or fourteen days after the ON transection. The optimal neuroprotective parameters were pulse duration of 1 and 2 ms/phase (P < 0.001, each), current intensity of 100 and 200 μA (P < 0.05, each), and stimulation frequency of 1, 5, and 20 Hz (P < 0.001, respectively). More than 30 min of TES was necessary to have a neuroprotective effect (P < 0.001). Symmetric pulses without an inter-pulse interval were most effective (P < 0.001). Repeated TES was more neuroprotective than a single TES at 14 days after ON transection (P < 0.001). Our results indicate that there is a range of optimal neuroprotective parameters of TES for axotomized RGCs of rats. These values will provide a guideline for the use of TES in patients with different retinal and optic nerve diseases.