Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice

AIM: To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice. METHODS: Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively. Pathological techniques were used to reveal the morphological changes of the anterior segment in Smad4 defective eye. Immunohistochemical staining was employed to observe the expression of E-cadherin, N-cadherin and α-SMA in anterior segment of Smad4 defective mice and control mice at embryonic (E) day 16.5. Real-time quantitative polymerase chain reaction (qPCR) was performed to detect the expression of Snail, Zeb1, Zeb2 and Twist2 in lens of Smad4 defective mice and control mice at E16.5. Statistical evaluations were performed using the unpaired Student’s t-test (two-tailed) by SPSS 11.0 software. RESULTS: Conditional deletion of Smad4 on eye surface ectoderm resulted in corneal dysplasia, iridocorneal angle closure, corneolenticular adhesions and cataract resembling Peters anomaly. Loss of Smad4 function inhibited E-cadherin expression in the lens epithelium cells and corneal epithelium cells in Smad4 defective eye. Expression of N-cadherin was up-regulated in corneal epithelium and corneal stroma. Both E-cadherin and N-cadherin were down-regulated at the future trabecular meshwork region in mutant eye. The qPCR results showed that the expression of Twist2 was increased significantly in the mutant lens (P<0.01). CONCLUSION: Smad4 is essential to eye development and likely a candidate pathogenic gene to Peters anomaly by regulating epithelial-mesenchymal transition. Twist2 can be regulated by Smad4 and plays an essential role in lens development.     

眼前段发育异常与相关基因

眼前段发育异常不仅累及眼前段组织结构的形态异常,还可能改变房水引流系统的代谢和生理,患者常伴随眼压升高,继而发生青光眼。与眼球发育有关的基因突变是造成这些异常的重要原因,而这些基因产物的信号转导通路又相互联系,形成复杂的网络体系。我们就眼前段发育相关基因的研究进行综述。     

Anterior segment dysgenesis in mosaic Turner syndrome

AIMS/BACKGROUND—Females with Turner syndrome commonly exhibit ophthalmological abnormalities, although there is little information in the literature documenting findings specific to Turner syndrome mosaics. Ophthalmic findings are described in four patients with mosaic Turner syndrome. All had anterior chamber abnormalities and all four had karyotypic abnormalities with a 45, X cell line. The possible relation between the karyotypic and the phenotypic findings in these patients is discussed.
METHODS—Four girls with mosaic Turner syndrome underwent a full ophthalmological assessment, including examination under anaesthesia where indicated.
RESULTS—Three of the four patients presented with congenital glaucoma. Two had the karyotype 45, X/46, X, idic(Y) and one a 45, X/47, XXX karyotype. The remaining child had a Rieger malformation of the iris and the karyotype 45, X/46, X, r(X).
CONCLUSIONS—These findings suggest that Turner syndrome mosaicism (where there are two abnormal cell lines) is associated with anterior segment dysgenesis. The findings in these four patients are compared with those seen in other mosaic phenotypes and it is postulated that the presence of two or more genetically different cell lines may have an adverse effect on anterior segment development.

     

Anterior segment dysgenesis and congenital glaucoma associated with partial trisomy of chromosome 1 (1q32-qter).

A child born with partial trisomy of chromosome 1 (1q32-qter) survived and was seen for anterior segment dysgenesis and congenital glaucoma. Pure trisomy 1q is rarely seen in live-born infants and has not previously been described in association with congenital glaucoma. The genetic basis for glaucoma is complicated and multifactorial and probably determined by a number of genes on a variety of chromosomes. The current case provides some evidence that part of chromosome 1 may be involved with the etiology of a glaucomatous process.     

Anterior segment mesenchymal dysgenesis associated with partial duplication of the short arm of chromosome 2

We present a case of partial duplication of the short arm of chromosome 2 (karyotype 46,XX, dup [2p21-2p25]) in a newborn girl. The infant was born at 41 weeks of gestation and died approximately 3 hours after birth. At autopsy the characteristic dysmorphic features (hypertelorism, high, prominent forehead, micrognathia and low-set, malformed ears) and numerous other congenital malformations were observed. Bilateral microcornea with opacities was noted. Histopathological examination of the eyes showed dysgenesis of Bowman's membrane, with glycosaminoglycan deposition and a series of structural anomalies that form part of the anterior segment mesenchymal dysgenesis (ASMD) complex. To our knowledge this is the first case of partial duplication of the short arm of chromosome 2 in which the ocular histopathological features have been studied. Our case provides a further example of the association of ASMD with a chromosomal abnormality.     

Anterior segment optical coherence tomography in glaucoma

In recent years, the rapid development of diagnostic optic devices has generated optical coherence tomography (OCT) as a new, non-invasive diagnostic method. With technical progress of the infrared spectrum at 1,310 nm, OCT of the anterior segment also became feasible. With anterior segment OCT different examinations which so far were ruled out by ultrasound in contact manner could be executed in a non-contact technique: pachymetry, goniometry, illustration of iris and lens configuration as well as postoperative results after different glaucoma surgeries such as trabeculectomy, deep sclerectomy and glaucoma drainage devices. Additionally, anterior segment OCT provides an imaging device for experimental approaches in glaucoma. Today two commercially available units are available: SL OCT (Heidelberg Engineering, Heidelberg, Germany) und Visante(R) OCT (Zeiss Meditec, Jena, Germany). For all applications OCT delivered a high inter- and intraobserver reproducibility, is equal to ultrasound in accuracy and involves a higher patient comfort. Within the different applications, a direct comparison with ultrasound technique reveals minor differences depending on the device type. Therefore, it is advised to indicate the device type with all measurements. OCT enables precise, two-dimensional, non-contact imaging of the anterior segment in high resolution. For glaucomatous diseases, anterior segment OCT enlarges and enriches the armamentarium of glaucoma diagnostics and postoperative care of current modern glaucoma surgery.     

Anterior segment dysgenesis: Insights into the genetics and pathogenesis

Childhood glaucoma is a treatable cause of blindness, provided it is recognized, diagnosed, and treated in time. WHO has estimated that it is responsible for Blind Years second only to cataracts. The fundamental pathophysiology of all childhood glaucoma is impaired outflow through the trabecular meshwork. Anterior segment Dysgeneses (ASD) are a group of non-acquired ocular anomalies associated with glaucoma, characterized by developmental abnormalities of the tissues of the anterior segment. The cause is multifactorial, and many genes are involved in the development of the anterior segment. Over the last decade, molecular and developmental genetic research has transformed our understanding of the molecular basis of ASD and the developmental mechanisms underlying these conditions. Identifying the genetic changes underlying ASD has gradually led to the recognition that some of these conditions may be parts of a disease spectrum. The characterization of genes responsible for glaucoma is the critical first step toward developing diagnostic and screening tests, which could identify individuals at risk for disease before irreversible optic nerve damage occurs. It is also crucial for genetic counseling and risk stratification of later pregnancies. It also aids pre-natal testing by various methods allowing for effective genetic counseling. This review will summarize the known genetic variants associated with phenotypes of ASD and the possible significance and utility of genetic testing in the clinic.     

Anterior segment imaging in glaucoma: An updated review

Anterior segment imaging allows for an objective method of visualizing the anterior segment angle. Two of the most commonly used devices for anterior segment imaging include the anterior segment optical coherence tomography (AS-OCT) and the ultrasound biomicroscopy (UBM). AS-OCT technology has several types, including time-domain, swept-source, and spectral-domain-based configurations. We performed a literature search on PubMed for articles containing the text “anterior segment OCT,” “ultrasound biomicroscopy,” and “anterior segment imaging” since 2004, with some pertinent references before 2004 included for completeness. This review compares the advantages and disadvantages of AS-OCT and UBM, and summarizes the most recent literature regarding the importance of these devices in glaucoma diagnosis and management. These devices not only aid in visualization of the angle, but also have important postsurgical applications in bleb and tube imaging.     

Anterior mesenchymal dysgenesis of the eye. Congenital hereditary endothelial dystrophy and congenital glaucoma

The present report describes a patient with congenital glaucoma and iris hypoplasia who underwent repeated surgery to control the glaucoma. Despite these procedures, the patient's corneas opacified progressively, and bilateral penetrating keratoplasties were performed. Histopathological studies, including transmission and scanning electro microscopy of the corneal buttons, demonstrated specific changes of Descemet's membrane and the endothelium typical of congenital hereditary endothelial dystrophy (CHED). CHED has usually been considered to be a specific clinical entity that is not combined with congenital glaucoma or other significant abnormalities of the anterior segment of the eye. The present case indicates that these conditions may be combined, which is of importance when dealing with infants with congenital glaucoma and corneal opacities.     

Primary glaucoma associated with iridotrabecular dysgenesis and ectropion uveae

We present nine patients with unilateral congenital ectropion uveae (hyperplasia of the iris pigment border), iris hypoplasia, characteristic gonioscopic findings, and glaucoma. A majority of these patients also demonstrated mild ptosis. In none of these patients were there any associated systemic abnormalities. The apparent ectropion uveae results from spread of the iris pigment epithelium beyond the iris ruff and onto the anterior surface of the iris. In two patients with this abnormality, histopathologic and electron microscopic findings are presented. All patients with congenital ectropion uveae should be carefully examined periodically to detect glaucoma.     

原发性急性闭角型青光眼周边虹膜切除和滤过性手术前后眼前段结构参数对比分析

目的 观察原发性急性闭角型青光眼(acute primary angle closure glaucoma,APACG)周边虹膜切除(peripheral iridectomy,PI)和小梁切除术(Trabeculectomy,Trab)手术前后眼前段结构参数的改变.方法 临床病例对照研究.对2009年6～12月在中山大学眼科中心连续性收集57例57只眼APACG患者,周边虹膜粘连(peripheral anterior synechiae,PAS)范围≤6个钟点者行PI术,PAS范围＞6个钟点者行小梁切除术,术前及术后3月行眼前段光学相干断层扫描仪(anterior segment optical coherence tomograph,AS-OCT)眼前段扫描.比较两组组内及组间术前及术后的中央前房深度(central anterior chamber depth,ACD)、房角开放距离(angle opening distarce,AOD)、小梁网虹膜间面积(Trabecular iris area,TISA)、房角隐窝面积(angle recess area,ARA)、前房宽度(anterior chamber width,ACW)、前房容积(anterior chamber volume,ACV)和晶状体矢高(crystalline lens rise,CLR).结果 两组间的平均年龄(t=-0.176,P=0.862)和性别(P=0.390)之间无统计学差异.术前及术后周边虹膜切除术组的TISA和ARA均明显大于小梁切除术组(P=0.013～0.049).周边虹膜切除术组术后AOD、TISA、ARA及ACV较术前明显增加(P＜0.001～0.044),ACD、ACW及CLR手术前后无明显变化(P=0.102～0.609).小梁切除术组术后除ACV较术前的增加有统计学意义外(P＜0.001),余参数手术前后无变化(P=0.056～0.585).结论 周边虹膜切除术和小梁切除术均可增加APACG眼的ACV,但ACD和CLR无明显改变.周边虹膜切除术术后APACG眼房角参数改善,但小梁切除术对房角参数的改变无明显影响.

Abstract：

Objective To evaluate the changes in antenor segment configuration after peripheral iridectomy (PD or trabeculectomy (Trab) in acute primary angle closure glaucoma (APACG). Methods FiRy-seven eyes of 57 patients with APACG were successive collected. PI was performed to those patients with the clock hours of peripheral anterior synechiae (PAS) 6, while Trab was performed to those patients with the clock hours of PAS >6. Anterior segment optical coherence tomography (AS-OCT) examination was performed before and 3 months after PI/Trab to compare central anterior chamber depth (ACD), angle opening distance (AOD), trabecular iris area (TISA), angle recess area (ARA), anterior chamber width (ACW), anterior chamber volume (ACV) and crystalline lens rise (CLR). Results There were no differences in mean age (P 0.862) and male/female ratio (P=0.380) between the 2 groups. After surgery, AOD, TISA, ARA, ACA and ACV increased significantly (P ＜0.001～0.044), while no changes were found in ACD, ACW and CLR (P=0.102～0.609) in PI group. In Trab group, ACV increased significantly postoperation (P ＜0.001) while other parameters shown no changes. Conclusions Both surgery of PI and Trab can increase ACV; PI can improve the anterior angle parameters in APACG, but Trab surgery shows no changes of those parameters.     

Anterior segment complications and neovascular glaucoma following implantation of a posterior chamber intraocular lens

Lens implantation is now a highly successful operation. Although follow-up over 5 to 10 years with posterior chamber lenses is incomplete, the complication rate appears to be as low or lower than other lens styles. We present an exception: a clinicopathologic analysis of a globe, enucleated 4 years postoperatively, which in spite of uneventful implantation of a posterior chamber lens, developed neovascular glaucoma. Microscopic studies suggest several mechanisms for this rare complication including deep erosion of a prolene loop into the ciliary body, anterior segment ischemia, and breakdown of the blood-aqueous barrier. Scanning microscopy showed cracking of this deeply embedded loop, a finding we interpret as possible stress cracking and/or oxidation. The more flexible loops now used in modern lenses may decrease the chance of deep erosion. Implantation of a loop in the capsular bag may minimize the danger of both erosion and loop degradation. Patients should be followed long-term in order to recognize and treat these rare, but potentially disastrous complications.     

眼前节相干光断层扫描在原发性闭角型青光眼诊治中的应用

眼前节相干光断层扫描(AS-OCT)是继超声生物显微镜(UBM)后又一种眼前段成像检测手段,其为无创性、非接触性,分辨率较UBM高。可测量包括角膜、前房、前房角、虹膜、晶状体等多个眼前段结构参数。本文评价了AS-OCT在原发性闭角型青光眼(PACG)诊治中利用AS-OCT了解PACG和正常人眼前段生物学参数的差异,了解周边虹膜切开(或切除)术后、小梁切除术后、白内障手术后PACG的眼前段结构性参数的变化,以及对小梁切除术后滤过泡功能进行评估等,强调AS-OCT在PACG的诊断、发病机制、治疗观察中具有重要的临床应用价值。     

Anterior segment fluorescein angiography for evaluating the effect of vitrectomy for neovascular glaucoma

PURPOSE: Using anterior segment fluorescein angiography(AFA), we evaluated the relationship between the effect of vitrectomy combined with endophotocoagulation for neovascular glaucoma and the postoperative angiographic changes. SUBJECTS AND METHODS: Seven eyes of 7 patients (six eyes of 6 patients had proliferative diabetic retinopathy and 1 eye of 1 patient had central retinal vein occlusion) with neovascular glaucoma underwent both vitrectomy combined with endophotocoagulation and AFA before and after surgery. RESULTS: Of the 7 cases, the three eyes(42.9%), ther received one vitreous surgery alone had a reduction in intraocular pressure (IOP). The other 4 with uncontrollable IOP underwent trabeculectomy additionally, and three of them achieved good control of IOP. AFA showed less dye leakage in the iris after surgery in all cases. Three of 4 eyes with less dye leakage in the chamber angle showed good IOP control. Two of 3 eyes without the change in dye leakage were treated additionally by trabeculectomy. CONCLUSION: AFA is a sensitive technique in the assessment of neovascularization in the anterior segment, so that it is useful in evaluating the effect of vitrectomy combined with endophotocoagulation for neovascular glaucoma.