Anterior Zonules Research Articles

Remnants of the Anterior Tunica Vasculosa Lentis and Long Anterior Lens Zonules

To investigate presence of remnants of the tunica vasculosa lentis, a possible indication of anterior segment dysgenesis, in subjects with the long anterior zonule (LAZ) trait. Retroillumination photographs of the pupil region had been collected in earlier study of the LAZ trait in African Americans. Secondary image analysis was performed to assess the frequency of intact persistent pupillary membrane iris strands (PPMIS). The analysis included 148 subjects, comprised of 74 LAZ subjects (median age=70 y; range, 50 to 91 y; 64 females) and 74 controls (68 y; 50 to 83 y; 64 females). While controlling for age and sex, analysis showed that LAZ subjects were 3.1 times more likely than controls (odds ratio=3.1; 95% confidence interval, 1.4-6.7; P=0.004) to exhibit PPMIS in at least one of their eyes. The LAZ trait, which is being studied as a potential risk factor for glaucoma, was associated with presence of PPMIS in our study population.

Investigating Ocular Dimensions in African Americans With Long Anterior Zonules

To investigate ocular dimensions in African Americans with the long anterior zonule (LAZ) trait. A total of 61 African American LAZ subjects and 61 age-matched, race-matched, and sex-matched controls were compared with respect to central corneal thickness, central corneal curvature, axial length (AL), and subjective refraction. LAZ right eyes had a mean SR=+1.75±1.82 D and were 1.58 D (95% confidence interval, 0.83-2.31 D, P<0.0001) more hyperopic on average when compared with the control right eyes. LAZ right eyes also had an AL that was 0.69 mm (95% confidence interval, 0.34-1.04 mm, P<0.001) shorter on average than control right eyes. Similar results were found for left eyes. No differences were found with respect to central corneal curvature and central corneal thickness (P>0.05). In this data set, LAZ eyes tended to be more hyperopic and had ALs that were shorter than control eyes, characteristics that are consistent with elevated risk for angle-closure glaucoma.

Computer-animated model of accommodation and theory of reciprocal zonular action

This report presents a computer-animated model of the structures of accommodation based on new understanding of the anatomy of the zonular apparatus integrated with current understanding of the mechanism of accommodation. Analysis of this model suggests a new, consolidated theory of the mechanism of accommodation including a new theory of reciprocal zonular action. A three-dimensional animated model of the eye in accommodation and disaccommodation was produced in collaboration with an experienced medical animator. Current understanding of the anatomy of the zonule and the attachments of the vitreous zonule to the anterior hyaloid membrane is incomplete. Recent studies have demonstrated three components of the vitreous zonule: (1) anterior vitreous zonule (previously “hyalocapsular” zonule), which attaches the ciliary plexus in the valleys of the ciliary processes to the anterior hyaloid membrane in the region medial to the ciliary body and Weiger’s ligament; (2) intermediate vitreous zonule, which attaches the ciliary plexus to the anterior hyaloid peripherally; and (3) posterior vitreous zonule, which creates a sponge-like ring at the attachment zone that anchors the pars plana zonules. The pars plana zonules attach posteriorly to the elastic choroid above the ora serrata. Analysis of the computer-animated model demonstrates the synchronized movements of the accommodative structures in accommodation and disaccommodation. Utilizing model-based reasoning, it is shown that the posterior zonules attach to and provide traction to the anterior vitreous membrane and Weiger’s ligament. This model supports the concept that the ciliary body/zonule/anterior hyaloid complex contributes to the changes in the posterior lens capsule during accommodation, supporting an extralenticular component to accommodation and demonstrating an alternative to the “vitreous support” theories. There is a reciprocal action of the anterior zonules and the posterior zonules. During ciliary body contraction, the anterior zonules lose tension while the posterior zonules stretch and exert force on the posterior lens capsule playing a role in shaping the posterior lens thickness and curvature. During ciliary body relaxation, the posterior zonules lose tension as the lens flattens and is pulled back by the increasing tension of the anterior zonules.

Morphology and Accommodative Function of the Vitreous Zonule in Human and Monkey Eyes

To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans. Novel scanning electron microscopy (SEM) and ultrasound biomicroscopy (UBM) techniques were used to visualize the anterior, intermediate, and posterior vitreous zonule and their connections to the ciliary body, vitreous membrane, lens capsule, and ora serrata, and to characterize their age-related changes and correlate them with loss of accommodative forward movement of the ciliary body. alpha-Chymotrypsin was used focally to lyse the vitreous zonule and determine the effect on movement of the accommodative apparatus in monkeys. The vitreous attached to the peripheral lens capsule and the ora serrata directly. The pars plana zonule and the posterior tines of the anterior zonule were separated from the vitreous membrane except for strategically placed attachments, collectively termed the vitreous zonule, that may modulate and smooth the forward and backward movements of the entire system. Age-dependent changes in these relationships correlated significantly with loss of accommodative amplitude. Lysis of the intermediate vitreous zonule partially restored accommodative movement. The vitreous zonule system may help to smoothly translate to the lens the driving forces of accommodation and disaccommodation generated by the ciliary muscle, while maintaining visual focus and protecting the lens capsule and ora serrata from acute tractional forces. Stiffening of the vitreous zonular system may contribute to age-related loss of accommodation and offer a therapeutic target for presbyopia.

Effect of Anterior Zonule Transection on the Change in Lens Diameter and Power in Cynomolgus Monkeys during Simulated Accommodation

To quantify the role of anterior zonular tension on the optomechanical lens response during simulation of accommodation in primates. Postmortem cynomolgus monkey eyes (n = 14; age range, 3.0-11.5 years) were dissected leaving intact the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a scleral rim. The lens was mounted in a lens-stretching system and stretched radially in step-wise fashion. The load, and the lens diameter and power were measured at each step and the diameter- and power-load relationships were quantified. The anterior zonular fibers were then transected, and the experiment was repeated. The equatorial lens diameter and lens optical power before and after zonular transection were compared. Stretching increased the lens diameter by 0.25 +/- 0.09 mm (median +/- interquartile range) before and 0.25 +/- 0.19 mm after zonular transection. Stretching decreased the lens power by 13.0 +/- 6.5 D before and 10.6 +/- 8.0 D after zonular transection. The load required to change the diameter of the lens by 1 mm decreased from 18.8 +/- 10.7 g before to 15.0 +/- 7.8 g after zonular transection. The absolute change in power per gram of loading decreased from 2.5 +/- 1.1 before to 2.0 +/- 1.2 D after zonular transection. The cynomolgus monkey lens retains a significant fraction of its accommodative ability after transection of the anterior zonules in simulated accommodation experiments.

Possible Association Between Long Anterior Lens Zonules and Plateau Iris Configuration

To report plateau iris configuration (PIC) in subjects who have the long anterior zonule (LAZ) clinical trait. Two elderly African American males who exhibited LAZ and had partial appositional angle closure persisting after laser iridotomy were imaged with high-resolution ultrasonography to examine for PIC. A third elderly LAZ subject who had narrow angles without closure was also imaged for PIC. Each subject was tested for a serine 163 arginine mutation (S163R) C1q tumor necrosis factor-related protein 5 gene (C1QTNF5/CTRP5) mutation, which may be associated with the LAZ phenotype. All 3 LAZ subjects also had PIC, an unlikely association due to chance alone. None carried the S163R CTRP5 mutation. LAZ and PIC may have association and require study because LAZ might be a useful indicator for an increased likelihood of PIC and risk of angle closure. Mutation other than CTRP5 S163R should also be considered for the LAZ trait, which could be an important phenotypic marker in genetic studies.

CTRP5 Is a Membrane-Associated and Secretory Protein in the RPE and Ciliary Body and the S163R Mutation of CTRP5 Impairs Its Secretion

In a prior study, a S163R mutation in the complement-1q tumor necrosis factor-related protein 5 (CTRP5/ C1QTNF5) was reported to be associated with early-onset long anterior zonules (LAZ) and late-onset retinal degeneration (L-ORD). The ocular tissues involved in the phenotype are the retinal pigment epithelium (RPE) in the posterior segment and ciliary epithelium (CE) and lens in the anterior segment. The purpose of this study was to characterize the spatial and temporal expression of the mouse Ctrp5 gene, determine tissue and subcellular localization, and study the effect of the S163R mutation. The expression of the Ctrp5 gene in the mouse was studied by quantitative (q)RT-PCR and in situ hybridization. CTRP5 protein expression and distribution were studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of wild-type and mutant CTRP5 in MDCK and COS-7 cells was determined by immunofluorescence and immunoblot analysis. A significant level of Ctrp5 expression was detected in the adult mouse in the ciliary body (CB) and RPE, and expression started at a very early stage of embryogenesis. Immunohistochemical analysis showed CTRP5 protein in the apical processes of the RPE and forming a hexagonal lattice associated with the RPE lateral membranes. In the ciliary body, CTRP5 was localized to the apical aspects of the CE, the region between the bilayered ciliary epithelial cells. The membrane association of CTRP5 in the RPE and CE was further confirmed by immunoelectron microscopy. Furthermore, cultured cells were used to show that the CTRP5 is a secretory protein and that its secretion is impaired by the S163R mutation. CTRP5, a secretory and membrane-associated protein, is localized to the lateral and apical membranes of the RPE and CB. Impaired secretion of the mutant protein may underlie the pathophysiology of L-ORD and LAZ.

Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from aCTRP5Gene Mutation

To identify the gene responsible for a complex ocular phenotype of late-onset macular degeneration, long anterior zonules (LAZ), and elevated intraocular pressure (IOP) and to study its expression. Ocular examination, visual field, fluorescein angiography, and electrophysiology testing were performed. One affected individual was treated with vitamin A. DNA from 55 family members (UM:H389) was used for linkage, mapping, and mutation analysis. Linkage analysis of macular degeneration and LAZ phenotypes was performed independently. Mutations in candidate genes were screened by sequencing. mRNA expression of CTRP5 and MFRP, which are bicistronic genes, was studied by semiquantitative RT-PCR (qRT-PCR) in various human tissues. CTRP5 expression was also evaluated by in situ hybridization. Affected members had LAZ detectable by the third decade and/or macular degeneration by the fourth to fifth decade. A six-month treatment with vitamin A shortened dark adaptation considerably in one affected member. Both conditions mapped independently with zero recombination to 11q23, with maximum lod scores of 3.31 for macular degeneration and 5.41 for LAZ. The same CTRP5 missense mutation was identified in all affected individuals. Retinal pigment epithelium (RPE) and ciliary epithelium (CE) showed highest CTRP5 transcript expression, which was also true for MFRP. CTRP5 tissue expression was confirmed by in situ hybridization. A single locus at 11q23 is implicated in a complex ocular phenotype involving RPE and CE, tissues of neuroectodermal origin. All individuals with either LAZ and/or macular degeneration carry the same CTRP5 S163R mutation, which is transmitted in autosomal dominant manner.

Long anterior zonules and pigment dispersion

Purpose To describe pigment dispersion associated with long anterior zonules. Design Multicenter observational case series. Methods Fifteen patients, seven of whom were treated for glaucoma or ocular hypertension, were identified with long anterior zonules and pigment dispersion. Transmission electron microscopy was performed on one anterior capsule specimen. Results All patients had anterior zonules that inserted centrally on the lens capsule. Signs of pigment dispersion included corneal endothelial pigmentation, loss of the pupillary ruff, and variable trabecular meshwork pigmentation. Ultrasound biomicroscopy verified the lack of posterior iris insertion and concavity. There was no exfoliation material. Transmission electron microscopy showed zonular lamellae with adherent pigment granules, and no exfoliation material. Conclusions Long anterior zonules inserted onto the central lens capsule may cause mechanical disruption of the pigment epithelium at the pupillary ruff and central iris leading to pigment dispersion.

Three-dimensional architecture of the suspensory apparatus of the lens of the Rhesus monkey

the three-dimensional ultrastructure of the lens suspensory apparatus and its supporting tissues were determined in the adult Rhesus monkey eye, Single zonular bundles (4–6 μm) composed of parallel oriented fibrils were traced from the lens surfaces to the ciliary body. There are four major tracts of zonular fibrils; the anterior lens to pars plana, the equatorial region to ciliary process, the posterior lens to pars plana, and the posterior lens to ciliary process to pars plana. The course and insertion patterns of the anterior and posterior zonules suggest separate functions. The anterior zonules are arranged in a pattern suited for anterior face contour changes required in accommodation. The posterior zonular pattern is better arranged for maintenance of lens position. The anterior hyaloid membrane is seen as a mesh-work of fibrils with attachments around the ora serrata and on the lens posterior. It also serves as a lens support structure. In contrast, the adjacent vitreous is composed of fibrils plus globular units which are probably hyaluronic acid. The construction of the ciliary processes, the inserting posterior zonules, and the circumferential fibrils between the ciliary processes form a complex capable of reversible response to ciliary muscle contraction. In the light of these findings, a reconsideration of the prineipal theories of accommodation is in order.