视网膜色素上皮与有关常见病

视网膜是眼球最重要的眼内组织,是视觉系统中的前哨。组织学上共分为十层,最外层为视网膜色素上皮,起源于视杯外层;其余九层为神经视网膜,由视杯内层分化而来。视网膜色素上皮(RPE)与神经视网膜(简称视网膜)相比,组织结构上看来相对简单,但功能上却十分复杂,其对视觉的影响至关紧要,必须予以重视。近代视觉研究中,视网膜色素上皮是众所关注的课题之     

老年人视网膜色素上皮脱离的分类和后果

作者研究了1976年～1981年年令在55岁以上患视网膜色素上皮脱离未经治疗的患者共57例64只眼。诊断标准是以视网膜色素上皮突起和荧光血管造影呈现视网膜色素上皮下间隙染色蓄积为依据。对可辨识的视网膜下新生血管,视网膜下出血,不能解释的局限性强荧光点,广泛的视网膜下渗出以及高度近视和影响视力的其它眼病均除外。研究     

与年龄相关性黄斑变性有关的细胞外沉积：视网膜下疣样沉积和网状假性玻璃膜疣

 脂蛋白来源的碎片等沉积物可沉积于视网膜光感受器和色素上皮细胞之间,称为网状假性玻璃膜疣或视网膜下疣样沉积。临床上非常常见,但易被误认为是玻璃膜疣。网状假性玻璃膜疣与III型脉络膜新生血管、外层视网膜萎缩等较为密切。（眼科,2022,31： 413-418）     

视网膜下间隙的病理

视网膜下间隙系指外以视网膜色素上皮(RPE)、内以外界膜为界的一个间隙,近端以位于视乳头周围的Kuhnt中间组织为界,远端以位于距齿缘的色素上皮和Muller细胞之间的细胞接头为界。每一个界限都有其特殊结构及对疾病的不同反应。作为视网膜下间隙外界的色素上皮也是血-视网膜屏障两个主要地点之一;另一个位于视网膜毛细血管内皮。RPE及其封闭小带(zonulae occludens)可阻止血浆蛋白和血流中其他大分子进入视网膜下间隙。然而从脉络膜循环带来的葡萄糖、氧和其他营养物质则可通过色素上皮供给视网膜外层。营养物质经过色素上皮的运输与经     

眼钝挫伤后脉络膜病变的荧光素血管造影和靛青绿血管造影的研究[英]

眼钝挫伤后最具特征性的眼底改变之一是视网膜混浊,损伤轻微者眼底荧光素血管造影（ＦＦＡ）未见外层血－视网膜屏障破坏,组织病理改变主要位于光感受器外节;较严重病例可见荧光素渗漏,除感觉视网膜损伤外还伴有视网膜色素上皮损害,感觉视网膜及视网膜色素上皮的损伤...     

提高对视网膜出血的分类及临床意义的认识

视网膜出血在临床上依据所沉积的不同层次间隙可分为玻璃体出血、玻璃体下出血、内界膜下出血、视网膜浅层出血、视网膜深层出血、视网膜下出血和视网膜色素上皮下出血等七类。掌握不同类型视网膜出血的表现特征对疾病的诊断、鉴别诊断与指导治疗有重要价值。（眼科，2009，18：221—224）     

视网膜外层结构与视网膜疾病视功能预后的新认识

随着近年来光学相干断层扫描（opticalcoherencetomography,OCT）技术的发展,视网膜细微结构更多的细节可被观察。在视网膜外层的OCT成像中有四条高反射线,即外界膜（externallimitingmembrane,ELM）、内节／外节交界区（innersegment／outersegmentjunction,IS／OS）、锥细胞外节末端（coneoutersegmenttips,COST）和视网膜色素上皮（retinalpigmentepithelium,RPE）,这些高反射线的完整性与各种视网膜疾病的视力等功能相关,能够提示疾病的预后。本文就OCT对视网膜外层结构显像及其与常见视网膜疾病治疗后视功能恢复的关系进行综述。     

外层视网膜管状结构的研究进展

外层视网膜管状结构(ORT)是指在频域相干光层析成像术(SD-OCT)中观察到的位于视网膜外核层的圆形或类圆形、边缘高反射信号而内腔相对低反射信号的异常结构,伴有局部视网膜外界膜中断、卷曲及视网膜色素上皮萎缩。组织病理学研究认为ORT是光感受器细胞和外层视网膜在病理条件下发生的重构,是外层视网膜严重损伤的表现。ORT可见于多种视网膜退行性疾病的终末阶段,在年龄相关性黄斑变性中较为常见,且随着随访时间的延长逐渐增多。ORT在SD-OCT中的形态与视网膜内积液或囊样水肿有一定相似之处,但其并不是新生血管活动和再治疗的依据,且对抗血管内皮生长因子治疗反应不佳,视力预后较差。因此充分认识ORT,对临床开展相关眼底病治疗、判断预后十分重要。本文对目前有关ORT的组织病理学研究及临床研究的进展进行总结,以期为临床工作提供参考。     

视网膜色素上皮的形态与功能

视网膜色素上皮的形态与功能刘哲丽吴景天中国医科大学第一临床学院眼科（１１０００１）视网膜色素上皮（简称ＲＰＥ）为视网膜１０层结构中的最外层，由大小均等、形态规则的６～８角形细胞连续单层排列而成。外侧介于Ｂｒｕｃｈ膜与脉络膜相连，内侧与视细胞外节相连结...     

实验性视网膜下出血

老年性黄斑变性,近视,眼底血管样条纹,眼球钝挫伤,各种脉络膜视网膜病变如眼部拟组织胞浆菌病综合征,弓形体病,弓蛔虫病和结节病等均可导致黄斑部盘状变性。来源于脉络膜循环的新生血管,穿过Bruch膜在视网膜色素上皮下侵入视网膜下间隙。这些新生血管管壁菲薄,常引起视网膜色素上皮和视网膜发生浆液或出血性脱离,最后形成纤维瘢痕,相应的视网膜受到破坏。作者为模拟黄斑盘状变性的出血性视     

Peripapillary chorioretinal atrophy: Bruch's membrane changes and photoreceptor loss

PURPOSE: To determine relationships among Bruch's membrane ultrastructure, photoreceptor degeneration, and choriocapillaris atrophy with respect to zones of retinal pigment epithelium (RPE) degeneration and atrophy adjacent to the optic nerve head, as a function of age. DESIGN: Human tissue study using clinicopathologic correlation. TISSUES: Eyes from patients 36 to 93 years of age lacking clinical evidence of glaucoma, optic nerve abnormalities, severe myopia, age-related macular degeneration, or other macular or peripapillary chorioretinal pathologic condition. METHODS: Sections through the retina-choroid complex at the temporal aspect of the optic nerve head were used for light microscopic histopathologic analysis (n = 17), electron microscopy (n = 9), carbonic anhydrase histochemical analysis (n = 7), and lipid histochemical analysis (n = 22). Retinal whole mounts were used for photoreceptor counts (n = 5). MAIN OUTCOME MEASURES: We determined the width of RPE degeneration and atrophy, the number of eyes with abnormalities of inner Bruch's membrane, and the number of rod and cone photoreceptors within 1 mm of the disc margin. We determined whether Bruch's membrane changes, photoreceptor degeneration, and choriocapillaris atrophy were associated with RPE degeneration and atrophy. RESULTS: All eyes had peripapillary RPE atrophy, degeneration, or both. The zone of RPE atrophy widened significantly after age 75. Thickening of inner Bruch's membrane and abnormalities of the RPE basal lamina were associated with degenerating and atrophic RPE in all eyes. The RPE basal lamina was narrow, reduplicated, or thickened as a basal laminar deposit. All eyes exhibited degeneration and loss of rods but not cones at the peripapillary termination of Bruch's membrane. Diminution of choriocapillaris coverage of Bruch's membrane was associated with RPE degeneration. Complete loss of the choriocapillaris was associated with RPE atrophy. CONCLUSIONS: Our results suggest that peripapillary chorioretinal atrophy is an age-related degeneration of the RPE-Bruch's membrane complex that resembles that found in the macula and periphery of normal eyes.     

Relationship of Basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration

PURPOSE: To correlate basal laminar deposit (BLamD) and membranous debris, including basal linear deposit (BLinD), with the evolution of early age-related macular degeneration (AMD). METHODS: A clinicopathologic collection of 132 eyes with a continuous layer of BLamD was reviewed. The thickness and type of BLamD and the sites of membranous debris deposition were correlated with the clinical progression of the disease. RESULTS: Two types of BLamD, termed early and late, were identified based on light microscopic appearance by using the picro-Mallory stain. The progressive accumulation of late type BLamD correlated well with increasing BLamD thickness, advancing RPE degeneration, poorer vision, increasing age, and clinically evident pigment changes. Membranous debris initially accumulated diffusely as BLinD, most eyes with BLinD and early BLamD remaining funduscopically normal. However, membranous debris also formed focal collections as basal mounds internal to the RPE basement membrane and as soft drusen external to the basement membrane. Eyes in which membranous debris remained confined to basal mounds belonged to older patients with poorer vision, whereas patients with soft drusen were younger and had better vision. CONCLUSIONS: The presence of BLinD and early BLamD define threshold AMD, which manifests clinically as a normal fundus. Although late BLamD correlates most closely with clinical pigment abnormalities, it is the quantity and sites of membranous debris accumulation that appear to determine whether the disease develops pigment changes only or follows the alternative pathway of soft drusen formation with its attendant greater risk of choroidal neovascularization (CNV).     

Immunohistochemical light and electron microscopy of basal laminar deposit

The formation of basal laminar deposit (BLD) is one of the histopathologic changes in the aging human macula. BLD is assumed to be an early stage of age-related macular degeneration. The location of BLD, between the RPE plasma membrane and its basement membrane and in the outer collagenous zone of Bruch's membrane, and its ultrastructure suggest that it is composed of excessive amounts of basement membrane material. The main components of basement membranes are type IV collagen, heparan sulfate proteoglycans (HSPG) and laminin. Labeled antibodies against these components can therefore be used for the identification and localization of basement membrane material by means of immunohistochemical techniques. In this study the presence of type IV collagen, laminin and HSPG was determined in aged human maculae by immunohistochemistry and immunoelectron microscopy. Tests for the presence of type VI collagen and fibronectin were also performed. We obtained 76 eyes from 68 human subjects at autopsy or after surgical enucleation for anteriorly located choroidal melanomas. The finely granular component of BLD stained positive with antibodies against type IV collagen, HSPG and laminin, but the long-spacing collagen component of BED did not. Neither component of BED was stained with antibodies against type VI collagen or fibronectin. We conclude that BLD consists partly of excess basement membrane material.     

Aging changes in Bruch's membrane of monkeys: an electron microscopic study

Bruch's membrane from monkeys of various ages was studied by electron microscopy. In monkeys under 15 years of age, Bruch's membrane rarely contained a small amount of polymorphous material that did not appear to increase with advancing age up to 15 years. However, the polymorphous material did increase over 20 years of age. The accumulation of vesicular, granular, tubular and linear polymorphous material in Bruch's membrane was though to be a result of evagination of a minimal portion of a retinal pigment epithelial (RPE) cell between adjacent basal infoldings, and its subsequent degeneration. The plasma membrane of the evagination seemed to be the primary source of the tubular or linear material, vesicles the main source of vesicular material, and cytosol and basement membranes to be the source of the granular material. The fibrous long-spacing collagen was associated with the basement membrane of the choriocapillaris and RPE cells. The granular deposits between the plasma infoldings and the basement membrane of RPE cells may originate from the basement membrane of the RPE, and could be the initial lesion of basal linear deposits.     

Age-related components of Bruch's membrane in the human eye

Age-related deposits within the inner and outer collagenous zones (ICZ/OCZ) of Bruch's membrane have been studied in normal aged human eyes. Electron microscopic examination of tissue from the macular region of 28 post-mortem eyes has shown that age-related deposits comprise mainly coated membrane-bound (CMB) bodies and their fragments. These bodies appear to be released from the RPE via the basal plasma membrane. Morphometric analysis of the average thickness and distribution of age-related deposits has demonstrated that as the thickness of the deposit increases with age, the major part is contained within the OCZ. The ICZ shows only a minimal increase in thickness during life. These results suggest that in the normal ageing eye the inner layers of Bruch's membrane (RPE basement membrane, ICZ and elastic layer) permit an unimpeded flow of CMB bodies from the RPE through to the OCZ.     

Extracellular matrix ligands promote RPE attachment to inner Bruch's membrane

PURPOSE: To determine if resurfacing layers of human Bruch's membrane with extracellular matrix ligands increases adult human retinal pigment epithelium (RPE) attachment. METHODS: We removed successive layers of Bruch's membrane sequentially by mechanical or enzymatic means to expose the RPE basal lamina, inner collagen layer, and elastin layer. Each layer was coated with extracellular matrix proteins (4 microg/cm(2) laminin, 4 microg/cm(2) vitronectin, 20 microg/cm(2) fibronectin, 20 microg/cm(2) collagen IV) for 2 hrs at 37 degrees C. First passage adult human RPE (15000 cells/6 mm explant) were plated onto coated or uncoated Bruch's membrane layers and RPE attachment was measured 18 hrs later. RESULTS: The reattachment rate to basal lamina derived from younger (age < 50) donors was higher than older (age >/= 70) donors (56.2 +/- 4.8% versus 46.7 +/- 0.7% respectively; p < 0.05). Coating with laminin or collagen IV increased RPE attachment to older but not younger basal lamina. The reattachment rate to inner collagen derived from younger donors was higher than older donors (51.3 +/- 2.7% versus 37.4 +/- 1.7% respectively, p < 0.05). Coating with laminin, fibronectin or collagen IV increased RPE attachment to older but not younger inner collagen layer. Adding extracellular matrix ligands did not increase RPE attachment to elastin. CONCLUSIONS: RPE attachment is increased by adding ligands to the basal lamina or inner collagen layer but not to the elastin layer. This may be important if the elastin layer is exposed in AMD patients after submacular surgery.     

Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (AMD). Ocular tissues were obtained from eight aged control donors (age range, 75-86 years; mean age, 79.8 years) with no evidence or history of chorioretinal disease and from 12 donors diagnosed with AMD (age range, 61-105 years; mean age, 83.9 years). Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies. Binding of the antibodies was blocked by preincubation of the antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal blood vessels were identified with mouse anti-human CD-34 antibody in adjacent tissue sections. Three independent observers graded the immunohistochemical reaction product. The most prominent sites of VEGF and PEDF localization in aged control choroid were RPE-Bruch's membrane-choriocapillaris complex including RPE basal lamina, intercapillary septa, and choroidal stroma. There was no significant difference in immunostaining intensity and localization of VEGF and PEDF in aged control choroids. The most intense VEGF immunoreactivity was observed in leukocytes within blood vessels. AMD choroid had a similar pattern and intensity of VEGF immunostaining to that observed in aged controls. However, PEDF immunoreactivity was significantly lower in RPE cells (p=0.0073), RPE basal lamina (p=0.0141), Bruch's membrane (p<0.0001), and choroidal stroma (p=0.0161) of AMD choroids. The most intense PEDF immunoreactivity was observed in disciform scars. Drusen and basal laminar deposits (BLDs) were positive for VEGF and PEDF. In aged control subjects, VEGF and PEDF immunostaining was the most intense in RPE-Bruch's membrane-choriocapillaris complex. In AMD, PEDF was significantly lower in RPE cells, RPE basal lamina, Bruch's membrane and choroidal stroma. These data suggest that a critical balance exists between PEDF and VEGF, and PEDF may counteract the angiogenic potential of VEGF. The decrease in PEDF may disrupt the balance and be permissive for the formation of choroidal neovascularization (CNV) in AMD.     

Location, substructure, and composition of basal laminar drusen compared with drusen associated with aging and age-related macular degeneration

PURPOSE: To determine whether basal laminar drusen differ in their location, ultrastructure, or composition from drusen associated with aging and age-related macular degeneration. METHODS: A paraffin-embedded block from an eye of a patient with basal laminar drusen was obtained. Sections were examined immunohistochemically using a battery of antibodies and lectins directed against drusen-associated proteins and glycoconjugates, respectively. Thin sections were examined by electron microscopy and compared with eyes with age-related macular degeneration. RESULTS: Drusen in the eye with basal laminar drusen are located between the basal lamina of the retinal pigment epithelium and the inner collagenous layer of Bruch membrane, just as they are in age-related macular degeneration. Two distinct ultrastructural phenotypes are observed in the eye with basal laminar drusen; their substructure is indistinguishable from drusen phenotypes in age-related macular degeneration. Both basal laminar drusen and drusen associated with age-related macular degeneration are bound by the lectins Ricinis communis agglutinin and Arachis hypogea agglutinin (after neuraminidase digestion) and by antivitronectin, anti-HLA-DR, anti-serum amyloid P, and anti-C5 antibodies, but not by antibodies directed against basement membrane-associated heparan sulfate proteoglycan, laminin, fibrinogen, or collagen type IV. CONCLUSIONS: These data support the notion that cuticular or basal laminar drusen are similar to, and perhaps indistinguishable from, drusen associated with age-related macular degeneration and are not nodular or diffuse thickenings of Bruch membrane, as previously suggested. Thus, we suggest basal laminar drusen is a misnomer. This clinical phenotype should be identified as "early adult onset, grouped drusen" or by the eponym "Gass syndrome." Features of basal laminar drusen, such as uniform drusen size, clustered distribution, and angiographic features, do not appear to be related to differences in drusen location, composition, or substructure.     

Immunohistochemical characterization of surgically removed subfoveal fibrovascular membranes

Eighteen patients with age-related macular degeneration developed subfoveal membranes that were surgically removed and submitted for histopathological examination. Immunohistochemical techniques were performed, using a panel of monoclonal antibodies recognizing retinal pigment epithelial (RPE) cells, myofibroblasts, pericytes, endothelial cells, glial cells, smooth muscle cells and various types of macrophages. The PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied as a marker of proliferating cells. The specimens displayed a core of neovascular stroma surrounded by a rim of more fibrous tissue. All specimens contained abundant RPE cells that in some cases appeared to envelop part of the membrane. Most cases had basal laminar deposits and thickened basement membrane material adjacent to the RPE cells suggestive of parts of Bruch's membrane. Often this Bruchlike membrane appeared at the surgical margin, forming a surgical cleavage plane. Chronic inflammatory cells were abundant, but polymorphonuclear leukocytes were notably absent. Nearly all specimens contained myofibroblasts and various types of macrophages. The presence of myofibroblasts suggests subretinal membrane contraction, which may induce new breaks and other pathology in RPE layer and Bruch's membrane.This paper was presented in part at the 1993 annual meeting of ARVO, Sarasota, Florida     

Extracellular matrix alterations precede vascularization of the retinal pigment epithelium in dystrophic rats

In Royal College of Surgeons (RCS) rats, the defective retinal pigment epithelium (RPE) fails to phagocytose the shed outer segment membranes, and the photoreceptors degenerate. Following degeneration of the photoreceptors, neovascularization and vitreo-retinal membranes (VRMs) develop. Blood-retinal barrier abnormalities at the level of the RPE suggested that Bruch's membrane extracellular matrix filtration barriers might also be abnormal. To study the progression of RPE cell, extracellular matrix and vascular alterations in the dystrophic retina, we used the cationic tracer polyethyleneimine and electron microscope morphometric techniques. At two weeks in the RCS retina, the RPE and retinal vessels, and their basal laminae, appeared normal. By two months, the RPE was hypertrophic and duplicated in some areas, and flattened in others. The RPE basal lamina was thickened (171% of the control, p less than .01), and there were more anionic sites along the RPE basal surface (158% of the control, p less than .01). Patches of displaced basal lamina material appeared within the RPE basal infoldings. By four months and later numerous retinal vessels were present within the RPE layer. In addition, cords of migrating RPE cells surrounded presumptive new vessels branching from the RPE layer towards the inner limiting membrane. The RPE-associated vessels exhibited diaphragmed fenestrae and channels, unlike normal retinal vessels, and their basal laminae were marked by anionic sites. These observations of RPE and extracellular matrix changes prior to vascular proliferation, and VRM formation in the dystrophic retina suggest that the RPE-associated extracellular matrix changes may contribute to vascular alterations in the dystrophic retina. A preliminary report of these findings has been presented previously.