Ultrastructural observations of the anterior chamber angle tissues in congenital glaucoma]

18 trabeculectomy specimens of congenital glaucoma were examined by light and transmission electron microscopy with the finding that the primary anomalies in congenital glaucoma included the developmental defect of trabecular meshwork, excessive collagen fibrils in the trabecular matrix, shifting forward of ciliary muscle fibers, and persistent mesenchymal tissue in the chamber angle. The authors also pointed out the importance of the secondary lesions of the trabecular meshwork in the pathogenesis of congenital glaucoma.     

先天性青光眼小梁的光镜和超微结构

对13例(16眼)先天性青光眼手术切除的小梁样品进行了光镜和电镜观察。根据虹膜与小梁的位置变化,病变亦异。第一类:虹膜与小梁组织贴附者,小梁严重发育不全,偶见小梁间隙,小梁内皮细胞萎缩退化,胞质空泡变性,无Schlemm's管。第二类:无虹膜贴附的小梁组织,小梁轻度发育不全,小梁内皮细胞异常活跃,小梁间隙内有基膜样物质沉积。对虹膜与小梁的位置关系及虹膜对小梁结构发育的影响做了初步探索。     

Ultrastructural alterations in the aqueous outflow pathway of adult buphthalmic rabbits

The aqueous outflow pathway of adult rabbit eyes with congenital glaucoma (buphthalmos) was examined by light microscopy and by scanning and transmission electron microscopy. The morphology of the buphthalmic rabbit aqueous outflow pathway was markedly abnormal when examined at 6 months, 1 yr, and 2 yr displaying apparent loss and/or compression of the iris pillars, dilation of the intertrabecular spaces, loss of endothelial cell-to-cell association and disorganization of trabecular lamellae, and posterior displacement of the aqueous plexus. In addition, the trabecular meshwork lamellae were observed only adjacent to the sclera and the inner portion of the trabecular meshwork was limited to swirls of collagen with scattered cells. These morphological findings suggest that the disease process in the rabbit principally involves an alteration in the differentiation and maintenance of the structural integrity of the trabecular meshwork. The loss of structural support of the buphthalmic trabecular meshwork may be a factor in the wide variation in intraocular pressure and may allow for compression of the trabecular meshwork against the aqueous plexus.     

Familial cases of congenital microcoria associated with late onset congenital glaucoma and goniodysgenesis

We presented a familial case of congenital microcoria associated with late onset congenital glaucoma. The proband, a 36-year-old man, had abnormally small pupils with diameters of 3.5 mm in the right eye and 1.5 mm in the left. Mydriatics, such as 1.25% epinephrine, 5% neosynephrine, 5% tyramine, and 1% atropine did not dilate the pupils fully. The iris showed poor development of collarettes and crypts, and lacked circular contraction folds bilaterally. Gonioscopic examination revealed developmental anomalies of the anterior chamber angles in both eyes. Abundant iris processes, which fused together partially in the right and circumferentially in the left, inserted from the iris root onto the scleral spur or further near to the Schwalbe's line. Applanation tonometry measured high intraocular pressure in both eyes. The anterior chamber angle tissues obtained by trabeculectomy were studied histopathologically. In the trabecular meshwork, a thick endothelial meshwork with many layers of cells embedded in prominent extracellular materials was observed on the canal side. On the anterior chamber side, there were several layers of trabecular sheet. These findings indicate underdevelopment of the trabecular meshwork. We examined three generations of his family and found that 5 members showed bilateral congenital microcoria, and another, deceased, was said also to have had congenital microcoria. All 5 surviving patients (3 males and 2 females) with microcoria were found to have bilateral goniodysgenesis also. Two of the 5 were affected with bilateral late onset congenital glaucoma. The congenital disorders in this family, congenital microcoria and goniodysgenesis, appeared in close relation, and were transmitted by autosomal dominant inheritance.     

小梁网的干细胞移植治疗原发性开角型青光眼的研究进展

原发性开角型青光眼(primary open angle glaucoma,POAG)是以持续性眼压增高导致视神经损伤为主要临床表现的一种疾病,其发病机制复杂,尚未明确,现阶段临床治疗相对困难。影响眼内压(intraocular pressure,IOP)高低的重要因素是房水引流是否通畅,而房水引流途径中小梁网(trabecular meshwork,TM)起重要调控作用。TM细胞的形态、数量、结构和功能改变均可使房水外流阻力增大,从而导致IOP升高。研究证实诱导多功能干细胞(induced pluripotent stem cells,iPSCs)、骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)和脂肪干细胞(adipose-derived stem cells,ADSCs)已被用于TM细胞的分化和再生,为POAG小梁网的干细胞替代治疗提供可靠的细胞来源。近年研究发现,小梁网干细胞(trabecular meshwork stem cells,TMSCs)在分化为TM细胞方面具有绝对优势,为细胞移植治疗青光眼提供新的靶向,这标志着干细胞治疗POAG进入一个新纪元,为青光眼治疗带来新的曙光。本文将对不同种类干细胞的小梁网移植进行综述,为细胞移植治疗POAG提供新思路。     

Recent developments in understanding the pathophysiology of elevated intraocular pressure

PURPOSE OF REVIEW: The state of the actin cytoskeleton and adhesions of trabecular meshwork cells are important determinants of fluid outflow through the trabecular meshwork. Dysregulation of these subcellular structures or cell loss itself, is expected to adversely affect aqueous humour dynamics and intraocular pressure. This article reviews recent research into the regulation of the cytoskeleton and cell adhesions within the trabecular meshwork. RECENT FINDINGS: Key cytoskeleton regulatory pathways in trabecular meshwork cells and their extracellular matrix significantly influence outflow facility. Integrins and matrix proteins play an important part in cell-matrix communication and mediate trabecular meshwork cytoskeletal changes. Increased cross-linking of the actin cytoskeleton may render the trabecular meshwork stiffer and more resistant to aqueous outflow. In-vitro studies show that transforming growth factor-beta induces actin stress fibres in trabecular meshwork cells, indicating that the cells become more contractile. Myocilin and the heparin II domain of fibronectin also influence the actin cytoskeleton. Mutated myocilin appears to affect trabecular meshwork cells differently from wild-type myocilin and can reduce cell survival. Reduced cell survival is also associated with primary open angle glaucoma, ageing, cellular senescence and oxidative insults. SUMMARY: These findings represent advances in understanding physiological and pathogenic mechanisms within the trabecular meshwork that are relevant to intraocular pressure regulation in health and glaucoma. They pave the way for future research on the pathogenesis of glaucoma and new targets for glaucoma therapy.     

Advanced juvenile open-angle glaucoma in an 8-year-old Haitian girl.

BACKGROUND: Glaucoma can afflict infants and children in several ways. Conditions such as inflammation or trauma can contribute to elevated intraocular pressure in secondary glaucoma, whereas congenital abnormalities of the trabecular meshwork development can result in infantile glaucoma. Lesser known, however, is juvenile open-angle glaucoma, which afflicts children and young adults in a manner similar to primary open-angle glaucoma, with no identifiable trabecular meshwork abnormalities or other secondary causes. CASE REPORT: An 8-year-old Haitian girl was referred for suspicion of a left optic neuropathy. Examination found markedly elevated intraocular pressure with open angles and advanced glaucomatous neuropathy in each eye without evidence of signs of infantile or secondary glaucoma. Medical therapy was instituted before surgical consultation. Clinical features of patients with juvenile open-angle glaucoma are presented along with a discussion of genetic expression and management of the condition. CONCLUSIONS: Juvenile open-angle glaucoma, although uncommon, can cause significant visual morbidity in children. In that children represent a unique and atypical glaucoma population with special therapeutic needs, all treatment options must be clearly understood.     

Morphological variability of the trabecular meshwork in glaucoma patients: implications for non-perforating glaucoma surgery

BACKGROUND/AIMS: Morphological variability of the trabecular meshwork could be of considerable importance for the proper intraoperative outcome of non-perforating antiglaucomatous surgery, such as deep sclerectomy and viscocanalostomy. The aim of this study was therefore to assess qualitative and quantitative characteristics of the trabecular meshwork in glaucoma patients undergoing trabeculectomy. METHODS: Trabeculectomy specimens from 177 glaucoma patients were prepared for light microscopy; 100 specimens were found to be suitable for qualitative assessment and quantitative computerised image analysis; measurements were taken of the meridional diameter of Schlemm's canal as well as the thickness of the trabecular meshwork at different positions. RESULTS: The mean meridional diameter of Schlemm's canal was 290 microm with the smallest values in the young patients with infantile and secondary glaucomas. the thickness of the trabecular meshwork ranged between 50-70 microm in the anterior region and between 100-130 microm for the posterior portion. The thickness of the anterior meshwork significantly decreased with age. The pigmentation of excised trabecular meshwork was found to be weak or even lacking in 68 patients. In 20 glaucoma patients the uveal meshwork was covered by an endothelial layer. CONCLUSIONS: From the morphological point of view the risk of inadvertent perforation during deep sclerectomy in older, white glaucoma patients should be taken into account even by an experienced surgeon, because the anterior meshwork in these cases is very thin and trabecular pigmentation that can be used as a topographic landmark is often lacking. The functional success of non-perforating glaucoma surgery in many patients may be limited by endothelial covering of the trabecular meshwork.     

水通道蛋白-1在小梁切除术之切除组织中的表达

目的观察青光跟患者小梁和虹膜组织与正常跟组织水通道蛋白-1（AQP-1）的表达差异。方法收集开角型和闭角型青光跟小梁切除术时切除的小梁和虹膜组织，免疫组织化学法检测AQP-1的表达，并与正常跟相应组织对照。结果正常眼小梁网组织、Schlemm’s管内皮细胞、周边虹膜组织中上皮和基质组织可见AQP-1呈强阳性着色，开角型青光眼和闭角型青光眼组织标本小梁网AQP-1阳性染色较正常弱；部分急性闭角型青光眼患者周边虹膜组织标本上皮层较基质组织染色明显弱。结论开角型青光眼小梁网AQP-1的表达减少可能与小梁网的发育有关，闭角型青光眼虹膜上皮和小梁网AQP-1的表达减少可能与虹膜萎缩或高眼压有关。     

CD44反义寡核苷酸对人眼小梁细胞增生与凋亡的影响

目的观察CD44反义寡核苷酸封闭CD44基因表达对人眼小梁细胞增生与凋亡的影响,探讨黏附分子CD44在原发性开角型青光眼发病过程中可能的作用。方法采用硫代修饰的CD44反义寡核苷酸,通过脂质体介导转染体外培养的人眼小梁细胞。MTT法观察CD44反义寡核苷酸对人眼小梁细胞增生的影响。流式细胞仪检测CD44反义寡核苷酸封闭CD44基因表达对人眼小梁细胞凋亡的影响。结果3种浓度的CD44反义寡核苷酸对人眼小梁细胞的增生起抑制作用且呈浓度依赖性,浓度越高抑制作用越强,但对小梁细胞的凋亡起促进作用,浓度越高促凋亡作用越明显。结论CD44反义寡核苷酸封闭CD44基因表达后人眼小梁细胞增生作用受到抑制,小梁细胞的凋亡增加。黏附分子CD44可能通过影响小梁细胞的增生与凋亡过程参与了原发性开角型青光眼发病过程。     

What increases outflow resistance in primary open-angle glaucoma?

Intraocular pressure, the most critical risk factor for primary open-angle glaucoma is generated in the trabecular meshwork outflow pathways, which provide resistance to aqueous humor outflow. The resistance is increased in primary open-angle glaucoma, and changes in the quality and amount of the extracellular matrix in the juxtacanalicular region of the trabecular meshwork appear to be causatively involved. The extracellular matrix changes are very likely under control of transforming growth factor-beta2 (TGF-beta2), which is found at high concentrations in the aqueous humor of patients with primary open-angle glaucoma. Additional factors are thrombospondin-1, which activates TGF-beta2 in vivo, and connective tissue growth factor, which is an important downstream mediator of the effects of TGF-beta2 on trabecular meshwork extracellular matrix turnover. In contrast, bone morphogenetic protein-7 (BMP-7) strongly antagonizes fibrogenic actions of TGF-beta2 on human trabecular meshwork cells, indicating that a pharmacological modulation of BMP-7 signalling might be a promising strategy to treat primary open-angle glaucoma.     

非编码RNA调控小梁网组织在青光眼中作用的研究进展

小梁网是前房水引流的重要通道,呈复杂的三维结构,主要的细胞成分是小梁网细胞,细胞之间有交错成多层的细胞外基质。小梁网结构和功能的改变是导致眼压失常甚至视神经损伤的重要原因。有研究发现,非编码RNA(ncRNA)的异常表达可导致小梁网细胞生存率、收缩性能和细胞外基质结构发生改变,房水流出受阻,眼压失控,是青光眼发生的重要机制。目前,与小梁网相关的ncRNA研究涉及多种ncRNA分子和多种类型青光眼,本文将对微小RNA、长链ncRNA和环状RNA等ncRNA在小梁网组织中的研究进展进行综述。     

Glaucoma in Sturge-Weber syndrome

Trabeculectomy specimens from three eyes with Sturge-Weber syndrome were examined histopathologically. Changes in the trabecular meshwork-Schlemm's canal system were similar to findings in old age and in primary open-angle glaucoma. Two mechanisms for glaucoma are theorized. In cases with buphthalmos and congenital glaucoma, the chamber angle is often anomalous, as in other types of congenital glaucoma. In later onset juvenile cases, the chamber angle more often appears normal. A premature aging of the trabecular meshwork Schlemm's canal complex, as shown by us histopathologically, is a primary cause of juvenile glaucoma. It is suggested that both mechanisms relate to the abnormal hemodynamics of episclera and chamber angle, due to persistence of Streeter's primordial vascular plexus.     

Neovascular tissue in the intertrabecular spaces in eyes with neovascular glaucoma.

AIMS/BACKGROUND: To investigate histological changes in the trabecular meshwork in eyes with neovascular glaucoma. METHODS: Light and electron microscopic studies were carried out on the trabecular meshwork of three enucleated eyes with neovascular glaucoma. The presence and distribution of factor VIII in the trabecular meshwork was assessed using the ABC method. RESULTS: Peripheral anterior synechiae covering the trabecular meshwork were detected in two eyes, which would explain the rise in intraocular pressure. In the third the angle was not completely closed by peripheral anterior synechiae. The spaces between the trabecular beams were lined by a single layer of vascular endothelium, and were filled with red blood cells in this patient. Factor VIII was positively stained in the endothelial cells, lining both these spaces and Schlemm's canal. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. CONCLUSION: The neovascular tissue found in the trabecular spaces might be one of the factors responsible for intraocular pressure elevation in eyes with neovascular glaucoma.     

Clinical and morphological studies in a case of congenital glaucoma combined with an ocular-dental-digital dysplasia (author's transl)]

Clinical and morphological studies were undertaken to characterize a case of congenital glaucoma combined with an ocular-dental-digital dysplasia in a two year old patient. Light and electromicroscopic investigations of a surgically removed trabecular specimen were carried out. A trabeculotomy had been performed at this exact site 10 months prior to removal. The existence of a canal of Schlemm was demonstrated. The regular trabecular meshwork and trabecular region was replaced by fairly dense scar tissue, containing rudimentary intertrabecular spaces. Proliferating corneal endothelial cells covered the wound area up to the uveal part of the trabecular region. The morphological findings correlated well with the clinical observation of continued raised intraocular pressure despite trabeculotomy. It is concluded that, contrary to the situation in adult onset glaucoma, the strong proliferative tendency of juvenile tissue has a marked influence on the postoperative efficacy of the trabeculotomy.     

微观直视下对房角结构阻滞部位与房水引流功能障碍的研究

通过110只原发性开角型青光眼的显微手术与一系列的检查观察,多数病例可以明确其房角结构的阻滞部位。其中单纯小梁网阻滞或单纯schlemm氏管阻滞都较少。S管腔与小梁网同时存在阻滞占大多数,特别晚期青光眼如此。当S管腔发生较广泛粘连而致严重阻滞时,其相应部位的小梁网与外集液管遭受相应的器质性阻滞而发生功能障碍。对小梁型、S管型、外集液管型青光眼的诊断要点,作了简要说明。     

糖皮质激素对小梁网的作用研究进展

应用糖皮质激素可引起眼压升高，它与原发性开角型青光眼关系密切。糖皮质激素对小梁网的作用可作为一个良好模型用于研究青光眼的发病机制。糖皮质激素对小梁网的作用是多方面的，它包括细胞外基质、细胞膜、细胞骨架及细胞核的多重变化。糖皮质激素受体的分子机制的新发现有助于从受体角度了解青光眼的发病机制。     

Diathermo-trabeculotomy ab externo: indications and long-term results.

The authors present the results of 2 years' observation of 47 eyes operated with diathermo-trabeculotomy ab externo. This technique, based on a diathermic effect in association with trabeculotomy ab externo, allows an ample opening of Schlemm's canal and of the trabecular meshwork, with normalisation of intraocular pressure and outflow facility, for a period of up to 2 years, in open-angle and congenital glaucoma.