非成像视觉环路对生理活动和行为的调控作用

视网膜神经节细胞(RGCs)是视网膜视觉信号输出到大脑的终极神经元, 可参与成像视觉(IFV)(图像形成)和非成像视觉(NIFV)(非图像形成)。视觉处理系统除了传递图像的视觉信息外, 传入的光信号对人的生理活动和行为也会产生影响, 称为NIFV。NIFV较少依赖于传统光感受器细胞产生的信号, 而是由视网膜上一类特殊的视网膜感光神经节细胞(ipRGCs)来完成。ipRGCs是RGCs中一类能表达感光黑视蛋白的细胞, 其轴突投射至特定核团, 参与调控多种NIFV行为, 从基础生理调节(如心率和瞳孔大小)到更复杂的行为调节(如昼夜节律), 甚至更高层次的认知过程(如焦虑等情绪)。NIFV环路是对光的重要反应, ipRGCs在NIFV环路中起着至关重要的作用。本文就NIFV环路对生理活动和行为的调控作用进行综述, 归纳ipRGCs投射核团与NIFV功能的关系, 以期为临床医生提供更加全面的视觉认识。     

自主感光视网膜神经节细胞与彩色光瞳孔测量

自主感光视网膜神经节细胞（ipRGCs）是除视杆细胞、视锥细胞以外的第三类光感受器细胞,位于视网膜内层,由于其内含黑视蛋白,故具备自主感光能力。瞳孔对光反应（PLR）主要由ipRGCs介导产生。ipRGCs可通过黑视蛋白直接感受光信号产生PLR,也可被来自视杆、视锥细胞的信号激活产生PLR。由于视杆细胞、视锥细胞和黑视蛋白产生的PLR各具特点,可采用不同强度和波长的光信号选择性刺激视杆细胞、视锥细胞和黑视蛋白,通过对产生的PLR进行分析可间接反映视杆细胞、视锥细胞和含黑视蛋白的ipRGCs的功能,这一方法称为彩色光瞳孔测量。现主要对ipRGCs介导PLR的通路、视杆/视锥细胞和黑视蛋白引起的PLR特点、彩色光瞳孔测量及其临床应用作一综述,希冀为相关眼科疾病的诊断及鉴别诊断提供新思路。     

新感光视蛋白视黑质的研究进展

视黑质是一种新近发现的、主要分布于视网膜神经节细胞的光感受器视蛋白,这一发现打破了一直以来持有的光感受器视蛋白仅分布于视杆和视锥细胞的观点。与经典的感光视蛋白功能不同,视黑质的主要功能是参与引发昼夜节律变化、瞳孔对光反应、体内激素水平的变化等非视觉成像光反应。本文就视黑质的形态和功能特点等作一综述。     

内在光敏性视网膜神经节细胞研究现状与展望

内在光敏性视网膜神经节细胞(ipRGC)是近20a来新发现的一类感光细胞。它们通过视色素黑视蛋白发挥感光功能，并将光信号传递至非成像功能脑区如视交叉上核(SCN)、橄榄前盖核(OPN)以控制昼夜节律光夹带和瞳孔对光反射； 还有少部分信号投射至大脑成像区域如背外侧膝状核(dLGN)和上丘(SC)参与成像视觉。目前已发现6种ipRGC亚型(M1～M6)，每种亚型都具有独特的形态和生理特性。这些细胞除了接收来自视杆细胞和视锥细胞的信号输入，也在视网膜内部通过化学突触和电突触调节视网膜内信号转导，在视觉信号传递和视觉发育中发挥重要作用。研究发现ipRGC与多种眼科及全身性疾病存在重要联系。由此可见这是一类复杂且重要的细胞类型，本文从ipRGC的发现、一般生理特性、信号转导和与疾病的关系等多方面进行综述。     

脑源性神经营养因子与视网膜神经节细胞

脑源性神经营养因子作为神经营养因子家族中的重要成员，广泛分布于中枢神经系统。视神经与视网膜是中枢神经系统的一部分，视网膜神经节细胞在视觉通路中起着重要的传导作用。脑源性神经营养因子作为一种靶源性神经营养因子和顺行性神经营养因子，在视网膜神经节细胞的生长发育过程中起重要调控作用，同时对损伤的视网膜神经节细胞有促进其存活及轴突生长的作用。     

干细胞移植治疗视网膜神经节细胞损伤性疾病的研究进展

视网膜神经节细胞是视觉形成的重要参与者。视网膜神经节细胞损伤或死亡往往会导致视功能不可逆转的损害。青光眼、糖尿病视网膜病变、高血压、视网膜变性等致盲性疾病,均会引起视网膜神经节细胞损伤或进行性大量凋亡。目前此类疾病在临床上尚无明确的治疗方法。为了恢复患者视网膜神经节细胞功能,国内外学者将研究焦点集中在干细胞移植上。干细胞移植主要指两大类,一类是基于干细胞的替代治疗,另一类则是通过干细胞移植促进某些因子分泌来保护视网膜神经节细胞。我们旨在对干细胞移植治疗视网膜神经节细胞损伤疾病的潜力进行综述,并着重讨论不同种干细胞分化为视网膜神经节细胞的研究进展。     

一种稳定标记小鼠视网膜内两种不同类型神经节细胞的方法

目的 报道一种简单高效显示小鼠视网膜中两种不同类型神经节细胞的方法.方法 利用特殊标记物Brn3a和Melanopsin,通过视网膜铺片免疫荧光双标染色结合激光共聚焦显微镜,分别标记小鼠视网膜中普通视网膜神经节细胞和内在光敏视网膜神经节细胞.结果 免疫荧光染色结果表明,内在光敏视网膜神经节细胞与普通视网膜神经节细胞均位于视网膜节细胞层,相间互补分布.内在光敏视网膜神经节细胞数量较少,为普通视网膜神经节细胞的1％ ～2％,其轴突朝向视神经盘方向汇集,树突野较大,伸向内网层.结论 免疫荧光双标染色是小鼠视网膜内两种不同类型视网膜神经节细胞简单易行、稳定高效的标记方法.     

Müller细胞干细胞特性的研究进展

视网膜退行性病变缺少有效的防治方法.研究显示,Müller细胞可表达视网膜神经元细胞标记物如钙视网膜蛋白、视黄醛结合蛋白等.人Müller细胞不但可表达神经干细胞相关转录因子如SOX2、PAX6、CHX10、NOTCH1,还表达视网膜神经元标记物如双极细胞标记物蛋白激酶C,光感受器神经元标记物(盘膜边缘蛋白),神经节细胞标记物HuD与Brn3,大部分神经元标记物神经丝蛋白、βⅢ微管蛋白,神经节细胞、无长突细胞和水平细胞阳性标记物(钙视网膜蛋白).因此表明,视网膜Müller细胞可分化成不同视网膜神经元细胞,具有干细胞特性,利用Müller细胞进行细胞移植可能是治疗视网膜退行性病变具有潜力的新策略.     

视网膜神经节细胞谷氨酸毒性的防护研究

目前认为谷氨酸兴奋毒性是触发青光眼和／或视网膜缺血性神经节细胞损伤级联反应的最主要因素。大量研究表明，预防性阻断谷氨酸兴奋毒性可以保护视网膜神经节细胞，减少缺血损伤和神经节细胞凋亡。现就近年来抗谷氨酸毒性，保护视网膜神经节细胞的方法和药物作一简要综述。     

视网膜神经节细胞无血清上清培养液诱导大鼠视网膜干细胞的分化

目的　探讨视网膜神经节细胞无血清上清培养液对视网膜干细胞分化的影响。方法　分离大鼠视网膜干细胞和视网膜神经节细胞;采用免疫荧光法鉴定体外培养的大鼠视网膜干细胞与视网膜神经节细胞,视网膜干细胞以Nestin抗体进行鉴定,视网膜神经节细胞以Thy-1抗体进行鉴定;以视网膜神经节细胞无血清上清培养液培养视网膜干细胞,以不加入条件培养液培养的视网膜干细胞为对照组,收集分化细胞,采用qPCR法检测Nestin、Pax6、Thy-1及Brn-3的基因表达。结果　培养的视网膜干细胞Nestin抗体染色阳性,视网膜神经节细胞Thy-1抗体染色阳性。培养视网膜干细胞72 h后,与对照组相比,无血清上清培养液组细胞Nestin和PAX6基因相对表达量降低,差异均有统计学意义（均为P<0.000 1）;Thy-1和Brn-3基因相对表达量升高,差异均有统计学意义（均为P<0.05）。结论　视网膜神经节细胞无血清上清培养液能够诱导视网膜干细胞分化为视网膜神经节样细胞。     

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。     

Müller细胞在视网膜损伤中对视神经节细胞影响的研究进展

Müller细胞是视网膜中主要神经胶质细胞，贯穿视网膜全层。尽管近年来针对Müller细胞功能的研究较多，但是Müller细胞和视网膜神经节细胞(retinal ganglion cells，RGCs)的相互作用关系仍不完全清楚。目前已知生理状态下Müller细胞的许多功能和RGCs密切相关，例如Müller细胞已经证实为神经元祖细胞的来源，调节视网膜细胞间质K⁺水平和谷氨酸代谢，维持视网膜内能量代谢和营养支持等。在视网膜损伤时，Müller细胞相关功能对RGCs的影响也十分重要。因此，本文就此研究进展进行综述，以期为视网膜中视神经的保护治疗提供新的思路。     

Morphology of intrinsically photosensitive retinal ganglion cells: distinct photoreceptors from rod/cone photoreceptors北大核心CSCD

Objective: This study was to observe the morphology of live intrinsically photosensitive retinal ganglion cells (ipRGCs) at cellular level, and to explore their three-dimensional structure and responses to light in curved retina and the relationship with rod/cone photoreceptors. Methods: ipRGCs were identified according to the enhanced green fluorescent potein (EGFP) markers. Two hundred and sixty-three ipRGCs were videoed in mouse whole-mounted retina after strengthening with Lucifer Yellow from patch clamp electrodes. The dendrites and cell bodies were analyzed according to their sublayer-specific localization in inner plexiform layer and ganglion cell layer of curved retina. The relationship with rod/cone system was reconstructed and their functions were speculated. The animal feeding and use was in accordance with the standards set by the ARVO, and the experiment was approved by the Ethic Committee for Experimental Animal of Hubei University of Science and Technology. Results: The ipRGCs had strictly sublayer-specific localization in three sublayers of retinal inner plexiform layer. Each sublayer occupies full retina and form photosensitive surface, without any intermediate photosensitive dentric distribution between sublayers. Each ipRGC had randomly dentric distributions among the three sublayer curves, without the specific ON/OFF stratification. The photosensitive sublayers had absolutely perpendicular assignment related to cone/rod photoreceptors. The expression of melanopsin and spike-producing Ca2+ /Na+ channels were randomly distributed in M1, M2 and M3 cells. M4 and M5 cells shared the characteristic properties of conventional ganglion cells. Conclusions: In contrast to the rod/cone photoreceptors, ipRGCs form multiple-sublayer photosensitive curved surface, which are perpendicular to rod/cone photoreceptors, their photosensitive melanopsin and intrinsic spike-producing channels randomly occupy these specific sublayers, which suggest their distinct functions from rod/cone photoreceptors. Copyright © 2018 by the Chinese Medical Association.     

原发性闭角型青光眼遗传流行病学研究进展

青光眼是一种以眼压增高为特征的遗传异质性眼病，具有进行性不可逆转的视神经变性、视野典型性改变及视网膜神经节细胞丢失的特点。原发性闭角型青光眼（primary angle-closure glaucoma，PACG）是青光眼的主要类型，是全球最常见的高患病率和高致盲率的一类眼病，给患者家庭及社会带来了沉重的负担。近期经家系研究、病例对照研究等多种遗传流行病学研究方法证实，PACG具有明显的遗传倾向。随着人类遗传学研究的快速发展和研究技术的不断提高，近年来基于全基因组关联分析以及候选基因关联分析的PACG遗传流行病学研究越来越多，主要集中在PACG发病相关的易感基因的研究，本文就PACG相关研究背景及遗传流行病学研究进展进行综述。     

视神经再生的实验研究进展

视神经是中枢神经的一部分，损伤后将无法再生，继而引起进一步视力损害。根据目前视神经损伤后视网膜神经节细胞（retinal ganglion cells，RGCs）轴突再生的基础研究，视神经损伤后必须采取以下有效措施:提高RGCs内在的再生潜力，改善生长抑制环境，优化RGCs神经再生，而诱导再生轴突靶向延伸是理想的促进视神经的再生与修复方式。本文查阅国内外最新实验性视神经再生研究类文献，从调控眼内炎症因子、提供合适外源性神秘生长因子、激活RGCs再生潜能、阻断抑制性轴突再生信号传导、给予适当的再生刺激信号、改善抑制性细胞外微环境等方面阐述促进视神经再生的研究现状，以期对早日实现基础研究成果尽快向临床应用转化有所帮助。     

Survival and remodeling of melanopsin cells during retinal dystrophy

The melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer retinal pathology (15 weeks of age). In particular, these cells express betaIII tubulin, alpha-acetylated tubulin, and microtubule-associated proteins (MAPs), while remaining negative for other RGC markers such as neurofilaments, calretinin, and parvalbumin. By 14 months of age, melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve vascular remodeling). The morphological abnormalities in melanopsin processes are associated with elevated immunoreactivity for MAP1b and a reduction in alpha-acetylated tubulin. Quantification of ipRGCs in whole mounts reveals reduced melanopsin cell number with increasing age. Focusing on the retinal periphery, we find a significant decline in melanopsin cell density contrasted by a stability of melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of melanopsin processes in the far peripheral retina, a structure that is coincident with a short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve vascular remodeling. However, a significant number of melanopsin positive cells survive into advanced stages of retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human retinal disease in order to preserve integrity of the inner retinal photoreceptive network.     

Melanopsin-dependent persistence and photopotentiation of murine pupillary light responses

PURPOSE: To determine the relative contributions of inner and outer retinal photoreception to the pupillary light response. METHODS: Wild-type, retinal degenerate (rd/rd), and melanopsin mutant (opn4(-/-)) mice were tested for pupillary light responsiveness by video pupillometry before, during, and after exposure to supersaturating light intensities. Similar lighting protocols were used to probe responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) recorded with multielectrode arrays ex vivo. RESULTS: Both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (intrinsically photosensitive retinal ganglion cells [ipRGCs]) are sufficient to drive the pupillary light response in mice. After supersaturating light exposure, rather than bleaching or adapting, rd/rd mice showed paradoxical potentiation of responses to subsaturating light exposure. opn4(-/-) mice, in contrast, could not sustain pupillary constriction under continuous bright illumination, and showed desensitization after bright-light exposure. Both the intensity of light necessary to induce potentiation and the spectral sensitivity for sustained and potentiated responses differed from that necessary to trigger pupillary constriction, suggesting that photopotentiation is dependent on a pigment-state distinct from that triggering the pupillary light response itself. Multielectrode array recordings of ipRGCs from rd/rd retinas demonstrated persistent cell firing under continuous light exposure but did not show potentiation. CONCLUSIONS: Unique photoreceptive properties of intrinsically photosensitive RGCs confer resistance to bleaching and/or adaptation under continuous bright illumination to the pupillary light response and suggest the presence of a photopigment with multiple absorption states.     

Amacrine Cells Forming Gap Junctions With Intrinsically Photosensitive Retinal Ganglion Cells: ipRGC Types,Neuromodulator Contents,and Connexin Isoform

PurposeIntrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only centrally to non-image-forming visual centers of the brain but also intraretinally to amacrine interneurons through gap junction electrical coupling, potentially modulating image-forming retinal processing. We aimed to determine (1) which ipRGC types couple with amacrine cells, (2) the neuromodulator contents of ipRGC-coupled amacrine cells, and (3) whether connexin36 (Cx36) contributes to ipRGC-amacrine coupling.MethodsGap junction–permeable Neurobiotin tracer was injected into green fluorescent protein (GFP)–labeled ipRGCs in Opn4^Cre/+; Z/EG mice to stain coupled amacrine cells, and immunohistochemistry was performed to reveal the neuromodulator contents of the Neurobiotin-stained amacrine cells. We also created Opn4^Cre/+; Cx36^flox/flox; Z/EG mice to knock out Cx36 in GFP-labeled ipRGCs and looked for changes in the number of ipRGC-coupled amacrine cells.ResultsSeventy-three percent of ipRGCs, including all six types (M1–M6), were tracer-coupled with amacrine somas 5.7 to 16.5 µm in diameter but not with ganglion cells. Ninety-two percent of the ipRGC-coupled somas were in the ganglion cell layer and the rest in the inner nuclear layer. Some ipRGC-coupled amacrine cells were found to accumulate serotonin or to contain nitric oxide synthase or neuropeptide Y. Knocking out Cx36 in M2 and M4 dramatically reduced the number of coupled somas.ConclusionsHeterologous gap junction coupling with amacrine cells is widespread across mouse ipRGC types. ipRGC-coupled amacrine cells probably comprise multiple morphologic types and use multiple neuromodulators, suggesting that gap junctional ipRGC-to-amacrine signaling likely exerts diverse modulatory effects on retinal physiology. ipRGC-amacrine coupling is mediated partly, but not solely, by Cx36.     

视神经炎的临床特征分析及早期视盘和黄斑的改变

目的　研究视神经炎患者的临床特征及早期视盘和黄斑的改变。方法　回顾性分析山西省眼科医院视神经炎患者67例85眼。分析患者基本情况、眼科检查结果及OCT检查结果。结果　67例85眼中，男24例，女43例；28例（41.8%）发生于冬季；49眼（57.6%）入院时最佳矫正视力小于1.7 logMAR。视神经脊髓炎抗体阳性者出院和入院时的最佳矫正视力均较髓鞘少突胶质糖蛋白抗体阳性者差。患眼较健眼视盘周围神经纤维层增厚，杯盘面积比、杯盘垂直比、杯盘水平比、杯容积减小，盘沿面积、视盘面积增大（均为P=0.000）；与健眼相比，患眼早期上方、下方和平均黄斑区神经节细胞层厚度及黄斑区神经节细胞复合体的局部丢失体积、整体丢失体积均未发生明显改变（均为P＞0.05）。视盘水肿与患眼平均视盘周围神经纤维层厚度存在正相关（r=0.728，P=0.000）。结论　视神经炎多发生于女性，早期视力损害严重，视神经脊髓炎抗体阳性者视力预后差。早期由于视盘水肿，视盘周围神经纤维层增厚，盘沿面积、视盘面积增大；杯容积、杯盘比减小，早期病变未累及黄斑区。