Why is glaucoma associated with exfoliation syndrome?

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by production and progressive accumulation of a fibrillar material in tissues throughout the anterior segment and also in connective tissue portions of various visceral organs. Mature exfoliation fibrils are composed of 8-10 nm microfibrils resembling elastic microfibrils. The exact chemical composition of exfoliation material (XFM) remains unknown. It appears to consist of a complex glycoprotein/ proteoglycan structure composed of a protein core surrounded by abundant glycoconjugates. The protein components include both non-collagenous basement membrane components and epitopes of the elastic fiber system, particularly components of elastic microfibrils. Overall, XFS is the most common identifiable cause of glaucoma, accounting for the majority of cases in some countries, and causing both open-angle glaucoma and angle-closure glaucoma. Iridolenticular friction leads to loss of XFM from the anterior lens surface and disruption of the iris pigment epithelium, resulting in pigment deposition in the trabecular meshwork, which also produces XFM locally. The primary cause of chronic pressure elevation appears to be the active involvement of trabecular cells and Schlemm's canal cells in particular, in the generalized pathologic matrix process with subsequent degenerative changes of Schlemm's canal and adjacent tissues. Narrow angles and angle-closure are common in XFS. Pupillary block may be caused by a combination of posterior synechiae, increased iris thickness or rigidity, or anterior lens movement secondary to zonular weakness or dialysis. Enlargement of the lens due to cataract formation and relative pupillary constriction are additional factors.     

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。     

Extracellular glycoproteins of the ocular trabecular zone in patients with primary open-angle glaucoma

The content of fibronectin, an extracellular glycoprotein, in the drainage out-flow system of human eyes was measured by the indirect immunoperoxidase staining technique. The degree of fibronectin accumulation in ocular tissues was evaluated by quantitative morphometric analysis. Fibronectin level in the ocular drainage system of humans grows with ageing and rapidly increases at different stages of primary open-angle glaucoma development. Increased deposit of fibronectin in trabecular tissue, mainly in the inner wall of Schlemm's canal and juxtacanalicular or cribriform part of trabecular meshwork, was demonstrated. A hypothesis explaining the development of the glaucomatous process by an adhesive impairment is proposed.     

Transient open-angle glaucoma associated with sickle cell trait: report of 4 cases.

Four black patients, all with sickle trait (SA), developed transient open-angle glaucoma with blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in the fourth no antecedent trauma was described. The intraocular pressure became normal in all 4 cases with the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal.     

Immunofluorescence studies of the human trabecular meshwork

Accumulation of extracellular material in the trabecular meshwork is responsible for increased resistance to outflow in the human eye. By means of the indirect immunofluorescence technique the authors detected extracellular collagen type IV, fibronectin and laminin in the trabecular meshwork and the wall of Schlemm's canal of glaucoma patients and controls. Collagen type IV is the so-called "basement membrane collagen" present in the lens capsule, Bowman's and Descemet's membranes. Fibronectin is a glycoprotein with many biologic activities; it can promote cell attachment and forms complexes with collagen. Laminin was isolated in 1979 and is present in the lamina lucida of basement membranes. The increased production and pathological metabolism of these three substances might be of some importance in the pathogenesis of primary open-angle glaucoma.     

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.     

原发性开角型青光眼非穿透小梁手术患者深层巩膜瓣及小梁膜的病理学观察

目的 研究原发性开角型青光眼患者(POAG)非穿透小梁手术的解剖学基础,探讨POAG患者房水外流的阻力部位及其病理改变。方法 选择行非穿透小梁手术的POAG患者12例(18只眼),取术中切除的深层巩膜瓣及撕除的外层小梁膜进行光镜、扫描电镜及透射电镜观察。结果 光镜观察标本见：深层巩膜瓣前端为少许深层角膜基质,并可见Schlemm管外壁单层内皮细胞。扫描电镜观察见：深层巩膜瓣内侧可见被打开的Schlemm管管腔和狭长的积液管开口;撕除膜小粱面可见角巩膜小粱的网状结构,排列致密,网眼较小,近管腔侧呈致密的板状结构。透射电镜观察见：Schlemm管外壁周围散在高电子密度物质;撕除膜包括Schlemm管内壁,邻管组织(内皮网)和部分角巩膜小梁,邻管组织细胞减少,细胞外基质增多,可见大量致密斑块沉积;角巩膜小粱网胶原板层结构增厚,弹力纤维增多,细胞体积增大,尤以细胞核增大明显。晚期患者的角巩膜小梁网内有致密斑块沉积,阻塞了小梁间隙。结论 非穿透小梁手术的深层巩膜瓣包括Schlemm管外壁,撕除膜包括邻管组织和部分角巩膜小梁。邻管组织和部分角巩膜小梁是POAG患者房水外流的主要阻力部位,同时Schlemm管外壁也是其重要构成部分。     

A case of Rubinstein-Taybi syndrome suspected with goniodysgenetic glaucoma

We reported a case of Rubinstein-Taybi syndrome suspected in association with goniodysgenetic glaucoma, and studied using light and electron microscopy the anterior chamber angle tissues obtained surgically by trabeculectomy. The patient was 31-year old male, who had a systemic appearance of Rubinstein-Taybi syndrome with dwarfism, mental retardation, antimongoloid slant, flat-broad based thumbs, low set ears, high arched plate except for whorl of dermatographism. In addition to these malformations, goniodysgenetic glaucoma was also present which is characterized by underdevelopment of the angle recess and invisible ciliary body band in gonioscopic examination. The histopathological studies of the specimens revealed the presence of a compact tissue filled with a large amount of collagen fibers with few cells in the juxta-canalicular tissue of Schlemm's canal. There were 3 to 4 layers of trabecular sheets of corneoscleral meshwork at the anterior chamber side of the compact tissue. We conclude that the presence of the compact tissue under Schlemm's canal represents goniodysgenesis, underdevelopment of the trabecular meshwork, which is the primary cause of the glaucoma in this case.     

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.     

The role of the actomyosin system in regulating trabecular fluid outflow

Abnormally high resistance to aqueous humor drainage via the trabecular meshwork and Schlemm's canal is highly correlated with the development of primary open-angle glaucoma. Contractility of the actomyosin system in the trabecular cells or inner wall endothelium of Schlemm's canal is an important factor in the regulation of outflow resistance. Cytoskeletal agents, affecting F-actin integrity or actomyosin contractility, or gene therapies, employing overexpression of caldesmon or Rho-A inhibition, can decrease outflow resistance in the drainage pathway. In this review, we discuss the mechanisms underlying these and similar effects on trabecular outflow resistance in living animals and/or in cultured ocular anterior segments from enucleated animal or human eyes.     

Physiology of aqueous humor outflow resistance: its relation to giant vacuoles

About 2% of the French population over the age of 40 suffers from open angle glaucoma, a disorder for which ocular hypertension is the main risk factor. Improving our understanding of primary open-angle glaucoma physiopathology has been an area of intense research for nearly a century. The main aqueous outflow system in the human eye includes the trabecular meshwork, Schlemm's canal, aqueous veins, and the episcleral veins. Schlemm's canal is bordered by endothelium cells, many of which contain giant vacuoles, structures that are sensitive to intraocular pressure and that therefore can act as markers of active outflow. Giant vacuoles are most often found near collector channels in normal eyes, probably in areas of low downstream pressure. In the glaucoma eye, determining where giant vacuoles form could help localize the site of pathological outflow resistance.     

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.     

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。     

Morphology of the trabecular meshwork three years after Erbium:YAG laser trabecular ablation.

Laser trabecular ablation (LTA) is an abinterno approach with the purpose to improve outflow facility by removing trabecular tissue and open Schlemm's canal. In a blind eye with secondary glaucoma following silicone oil surgery, Erbium:YAG LTA had been performed applying 12 neighboring single laser pulses (5-7 mJ pulse energy, 200 micros pulse duration) to the trabecular meshwork. Enucleation was performed three years after the procedure that did not achieve pressure control. Light-microscopy revealed neither marked scarring nor endothelial proliferation in the treated trabecular meshwork. However, most of the recognizable ablation craters failed to open Schlemm's canal. Although limited scar formation within the trabecular meshwork after LTA is a promising aspect, the present technique of Er:YAG LTA still needs technical and surgical improvements to guarantee reliable and reproducible openings of Schlemm's canal.     

Implantat in den Schlemm-Kanal Eine neue Methode, den intraokularen Druck bei Patienten mit primärem Offenwinkelglaukom zu regulieren?

BACKGROUND: A surgical technique was developed using a Schlemm's canal implant to bypass the obstruction of outflow of the juxtacanalicular trabecular meshwork in patients with primary open-angle glaucoma. The implant device should also bridge healing processes after trabeculotomy and laser techniques. PATIENTS AND METHODS: An 8- to 15-mm-long silicone tube was implanted in each of two human autopsy eyes connecting the anterior chamber directly with Schlemm's canal. Serial sectioning was performed at two sections of 1-mm length. RESULTS: Implantation of the tube was technically uneventful. Histological examination showed no evidence of mechanical disruption of the endothelial lining of the inner wall of Schlemm's canal. CONCLUSION: These preliminary results demonstrate the possibility of shunting aqueous directly into Schlemm's canal using a silicone tube. A clinical study in a selected group of patients is planned.     

Carbohydrate binding proteins galectin-1 and galectin-3 in human trabecular meshwork

PURPOSE: Galectins are a family of carbohydrate binding proteins involved in a variety of biological processes including cell-cell and cell-matrix interactions. We examined galectin-1 and galectin-3 to determine if galectins are expressed in the human trabecular meshwork and Schlemm's canal. METHODS: Human trabecular meshworks were dissected from donor eyes within 12 hr of death. Galectin-1 and galectin-3 expression was examined by RT-PCR and Western blot analysis. Immunohistochemistry of galectin-1 and galectin-3 was analyzed in normal and glaucomatous tissue. RESULTS: Expression of mRNA and protein of Galectin-1 (14 kDa) and galectin-3 (31 kDa) was found in the outflow pathway. Immunostaining revealed galectin-1 and galectin-3 throughout the meshwork, cells lining Schlemm's canal, and extracellular spaces in the inner and outer walls of the canal. Comparison of normal, POAG and PEX samples revealed no difference in location or intensity for either galectin-1 and galectin-3. CONCLUSION: Galectin-1 and galectin-3 are present in human trabecular meshwork of normal and glaucomatous eyes.     

Matricellular proteins in the trabecular meshwork

The trabecular meshwork is one of the primary tissues of interest in the normal regulation and dysregulation of intraocular pressure (IOP) that is a causative risk factor for primary open-angle glaucoma. Matricellular proteins generally function to allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). In non-ocular tissues, matricellular proteins generally increase fibrosis. Since ECM turnover is very important to the outflow facility, matricellular proteins may have a significant role in the regulation of IOP. The formalized study of matricellular proteins in trabecular meshwork is in its infancy. SPARC, thrombospondins-1 and -2, and tenascins-C and -X, and osteopontin have been localized to varying areas within the trabecular meshwork. Preliminary evidence indicates that SPARC and thrombospondin-1 play a role in the regulation of IOP and possibly the pathophysiology of glaucoma. These data show promise that matricellular proteins are involved in IOP dysregulation and are potential therapeutic targets. Further study is needed to clarify these roles.     

Anterior chamber angle vascularization in Sturge-Weber syndrome Report of a case

The case of a 20-year-old woman with a left-sided facial hemangioma and a homolateral glaucoma is reported, complete with the histology of a trabeculectomy specimen. Her left eye had an episcleral hemangioma and goniodysgenetic features in the anterior chamber angle, while the intraocular pressure was measured to be 45 mmHg. The left optic disc showed a large cupping and the left visual field was constricted. The right eye had no glaucomatous changes. Histological examination of the trabeculectomy specimen by both light and electron microscopy showed multiple congenital anomalies. There was a cluster of blood vessels in the trabecular meshwork. Abnormal accumulations of fine granular extracellular matrixes were observed in both the juxtacanalicular connective tissue and around the vascular structures. The lumen of Schlemm's canal was subdivided into three or four parts with few giant vacuole structures. The endothelial cells lining the inner wall of Schlemm's canal contained a well-formed basal lamina with many villi projecting into the lumen. These findings suggest that the multiple anomalies observed in the trabecular tissue may contribute to the manifestation of glaucoma in Sturge-Weber syndrome.     

Unilateral or asymmetric PEX syndrome? An electron microscopy study

BACKGROUND: The pseudoexfoliation (PEX) syndrome which is characterized by the accumulation of an abnormal extracellular material in intra- and extraocular tissues, clinically strictly manifests both unilateral and bilateral. However, the generalized nature of this matrix process does not support unilateral ocular manifestation. The aim of this study, therefore, was a detailed histopathological analysis of the apparently not involved fellow eyes in so-called "unilateral" PEX syndrome. MATERIAL AND METHODS: For transmission electron microscopy, 5 pairs of donor eyes with slitlamp-microscopic, macroscopic and light microscopic evidence of unilateral PEX syndrome and 6 normal control eyes were studied. For immunohistochemistry, light and electron microscopic antibodies against LTBP-1 and HNK-1, two well-known markers for PEX deposits, were used. RESULTS: All apparently not involved contralateral eyes showed ultrastructural changes in the iris, in the ciliary body and in the trabecular meshwork. These changes include deposits of typical PEX fibrils on iris and ciliary epithelia as well as in the iris dilator muscle, microfibrillar precursors in the periphery of iris vessels, degenerative changes of the iris pigment epithelium and of the dilator muscle and an increased accumulation of extracellular matrix components around iris vessels, in the dilator muscle and in the juxta-canalicular connective tissue of the trabecular meshwork. In all contralateral and PEX eyes, but not in the control eyes, LTBP-1 and HNK-1 positive deposits could be identified in the periphery of iris vessels and in the dilator by light- and electron microscopic immunolabeling. CONCLUSIONS: The observed alterations in contralateral eyes in so-called "unilateral" PEX syndrome support the concept that the PEX syndrome is a generalized, basically bilateral disease which may present in a clinically asymmetric manifestation. This should be considered in the clinical management of these patients.