Persistent anterior tunica vasculosa lentis in multisystemic smooth muscle dysfunction syndrome: A case report.

RATIONALE: Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a genetic disease that affects multiple organs. The report here concerns a patient with MSMDS, who is known so far as the youngest among all the reported patients. In addition to the typical manifestations, we observed previously unreported ocular abnormalities, including persistent anterior tunica vasculosa lentis (TVL) and early-onset retinal arteriolar tortuosity, by the fluorescein angiography (FA). PATIENT CONCERNS: The patient was admitted to the neonatal intensive care unit immediately after birth for a diagnosis of urinary system dysplasia during fetal life. After a thorough examination, the patient was found with patent ductus arteriosus, pulmonary hypertension, cerebrovascular disease, hypotonic bladder, intestinal malrotation, and congenital mydriasis. The FA of the eyes undertaken in her 6-week demonstrated perfused vasculature in the persistent anterior TVL and prominent retinal arteriolar tortuosity. The whole exome sequencing revealed a de novo heterozygous ACTA2 gene missense mutation p.R179H. DIAGNOSES: The patient was diagnosed with MSMDS. INTERVENTIONS: Follow-up observation. OUTCOMES: At the 3-month follow-up, no change of the ocular disease was observed. LESSONS: The persistent anterior TVL in this case implies that ACTA2 p.R179H mutation affects not only the smooth muscle cells but also the pericytes, and further affects the TVL regression. The prominent retinal arteriolar tortuosity in this 6-week-old infant indicates that the retinal arteriolar tortuosity can present early in MSMDS.

Proteomic analysis of aqueous humor from cataract patients with retinitis pigmentosa.

A postcataract surgery complication in patients with retinitis pigmentosa (RP) is lens capsular contraction. To identify potential proteins contributing to this phenomenon, high-performance liquid chromatography/mass spectrometry-based proteomic analysis was conducted with aqueous humor samples collected from 11 patients who underwent cataract surgeries, with four patients diagnosed as RP and cataract (RP group) and the other seven with only senile cataract group. The upregulated proteins in the RP group were enriched in wound response, while downregulated proteins were enriched in cell adhesion and lens crystallins. Receptors of two dramatically upregulated proteins tenascin-C (TNC) and serotransferrin were found expressed in human lens epithelial cells (HLEs). TNC can promote primary HLEs proliferation and cell line HLE-B3 migration. This study indicates aqueous humor proteomic analysis serves as an effective way to unveil the pathogenesis of RP complications. TNC is a potential target of stimulating HLEs proliferation in RP concomitant cataract patients that worth further research.

Ultrastructural and immunofluorescence analysis of anterior lens capsules in autosomal recessive Alport syndrome.

Background: To first report and study the ultrastructural and immunofluorescence abnormalities of the lens anterior capsules in a patient with autosomal recessive Alport syndrome.Methods: Two anterior lens capsules were collected in femtosecond laser-assisted cataract surgeries from a 29-year-old male patient with bilateral lenticonus caused by autosomal recessive Alport syndrome. The left capsule was examined by transmission electron microscopy and the right capsule was serial sectioned and stained with antibodies against the α2, α3, and α4 chains of type Ⅳ collagen. Anterior lens capsules of another two uncomplicated age-related cataract patients were collected and treated in the same way as the control.Results: The novel findings are that the mitochondria in lens epithelial cells in autosomal recessive Alport syndrome patients increased, twisted, and exhibited high electron density. Characteristic ultrastructure changes of capsule thinning, vertical dehiscence, and irregular-shaped lens epithelial cells were also observed in the left anterior lens capsule. Normal reactivity against the α2 chain and decreased reactivity against the α3 and α4 chains were observed in the right anterior lens capsule.Conclusions: The homozygous c.4599 T > G mutation of COL4A4 not only affects the formation of type Ⅳ collagen networks in the extracellular matrix, but also affects the morphology and survival of the lens epithelial cells in the patient with autosomal recessive Alport syndrome. This study is the first report of the ultrastructural and immunofluorescence changes of anterior lens capsules in autosomal recessive Alport syndrome.

Development of Animal Models for Lens and Corneal Diseases Using N-Methyl-N-Nitrosourea.

Purpose: N-methyl-N-nitrosourea (MNU) is an alkylating toxicant with potent mutagenic ability. This study was designed to induce apoptosis in lens epithelial cells (LECs) and corneal endothelial cells (CECs) via MNU administration. We sought to build ocular disease models of cataract and corneal endothelial decompensation. Methods: MNU was delivered into the intraperitoneal cavities of neonatal rats and the anterior chambers of adult rabbits. The MNU-treated animals were then subjected to a series of functional and morphological analyses at various time points. Results: MNU treatment induced pervasive apoptosis of LECs and CECs. These effects were dose and time dependent. Mature cataracts were found in neonatal rats 3 weeks after MNU treatment. Histological analysis revealed that MNU toxicity induced swelling, vacuolation, and liquefaction in lens fibers of MNU-treated rats. Pentacam examination showed that the average density of rat lens increased significantly after MNU administration. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) analysis showed pervasive apoptotic staining in the lenses of MNU-treated rats. In rabbit eyes, intracameral treatment with MNU induced corneal edema and significantly increased central corneal thickness, which peaked at P14. Morphological and immunohistochemical analysis showed that CECs were effectively ablated in the MNU-treated rabbits. The expression of 8-OHdG increased significantly in the cornea of MNU-treated rabbits, compared with vehicle-treated controls. Conclusions: MNU is sufficient to induce ocular cell apoptosis in animal models. These models of MNU-induced cataract and corneal endothelial decompensation represent valuable tools for efforts to develop relevant therapies.

Optic shrinkage and retraction in opacified hydrophilic acrylic intraocular lens: an anterior segment optical CT-based observation.

Intraocular lens (IOL) opacification is a rare phenomenon noted with hydrophilic acrylic IOLs. We report a case of advanced IOL opacification appreciated on anterior segment optical CT (ASOCT)as a shrunken biconcave optic retracted away from the posterior capsule (PC), unlike the other eye which had a clear biconvex IOL of similar material abutting the PC. After IOL exchange, the affected eye was noted to have more folds and Elschnig's pearls on the PC when compared with the other eye. Our case points towards rare IOL changes seen in advanced cases of opacification, their association with posterior capsular changes and the aid of ASOCT as a non-invasive tool in diagnosing them correctly.

Exfoliation Fibrils within the Basement Membrane of Anterior Lens Capsule: A Transmission Electron Microscopy Study.

Purpose: The aim of the present study was to demonstrate novel findings recognized within the basement membrane of the anterior lens capsules (ALCs) in exfoliation syndrome, in a transmission electron microscopy (TEM) study. Materials and methods: Twenty-one patients with age-related cataract were included in the study. Eleven out of them suffered from exfoliation syndrome (XFS). Anterior lens capsules were obtained from patients during phacoemulsification, applying continuous curvilinear capsulorhexis and then were examined by transmission electron microscope. Results: Six out of 11 examined basement membranes with XFS had a granular appearance with dotted deposits of electron-dense material. Fibrils were clearly detected, longitudinally, within the basement membrane, usually located in the outer quarter of the basement membrane, towards the anterior chamber. Conclusion: New data about the exfoliation material and its location within the basement membrane of the anterior lens capsules of XFS patients are presented. These findings constitute new evidence for XFS's histopathogenesis and might help clarify the lenticular exfoliation material's (XFM) mechanisms of origin.

Mutation in the mouse histone gene Hist2h3c1 leads to degeneration of the lens vesicle and severe microphthalmia.

During an ENU (N-ethyl-N-nitrosourea) mutagenesis screen, we observed a dominant small-eye mutant mouse with viable homozygotes. A corresponding mutant line was established and referred to as Aey69 (abnormality of the eye #69). Comprehensive phenotyping of the homozygous Aey69 mutants in the German Mouse Clinic revealed only a subset of statistically significant alterations between wild types and homozygous mutants. The mutation causes microphthalmia without a lens but with retinal hyperproliferation. Linkage was demonstrated to mouse chromosome 3 between the markers D3Mit188 and D3Mit11. Sequencing revealed a 358 A-> C mutation (Ile120Leu) in the Hist2h3c1 gene and a 71 T-> C (Val24Ala) mutation in the Gja8 gene. Detailed analysis of eye development in the homozygous mutant mice documented a perturbed lens development starting from the lens vesicle stage including decreasing expression of crystallins as well as of lens-specific transcription factors like PITX3 and FOXE3. In contrast, we observed an early expression of retinal progenitor cells characterized by several markers including BRN3 (retinal ganglion cells) and OTX2 (cone photoreceptors). The changes in the retina at the early embryonic stages of E11.5-E15.5 happen in parallel with apoptotic processes in the lens at the respective stages. The excessive retinal hyperproliferation is characterized by an increased level of Ki67. The hyperproliferation, however, does not disrupt the differentiation and appearance of the principal retinal cell types at postnatal stages, even if the overgrowing retina covers finally the entire bulbus of the eye. Morpholino-mediated knock-down of the hist2h3ca1 gene in zebrafish leads to a specific perturbation of lens development. When injected into zebrafish zygotes, only the mutant mouse mRNA leads to severe malformations, ranging from cyclopia to severe microphthalmia. The wild-type Hist2h3c1 mRNA can rescue the morpholino-induced defects corroborating its specific function in lens development. Based upon these data, it is concluded that the ocular function of the Hist2h3c1 gene (encoding a canonical H3.2 variant) is conserved throughout evolution. Moreover, the data highlight also the importance of Hist2h3c1 in the coordinated formation of lens and retina during eye development.

The Function of Thioredoxin-Binding Protein-2 (TBP-2) in Different Diseases.

Thioredoxin-binding protein-2 (TBP-2) has an important role in the redox system, but it plays a different role in many different diseases (e.g., various cancers, diabetes mellitus (DM), cardiovascular disease, and cataracts) by influencing cell proliferation, differentiation, apoptosis, autophagy, and metabolism. Distinct transcription factors (TFs) stimulated by different factors combine with binding sites or proteins to upregulate or downregulate TBP-2 expression, in order to respond to the change in the internal environment. Most research disclosed that the main function of TBP-2 is associating with thioredoxin (Trx) to inhibit the antioxidant capacity of Trx. Furthermore, the TBP-2 located in tissues, whether normal or abnormal, has the ability to cause the dysfunctioning of cells and even death through different pathways, such as shortening the cell cycle and inducing apoptosis or autophagy. Through these studies, we found that TBP-2 promoted the development of diseases which are involved in inflammatory and oxidative damage. To a certain extent, we believe that there is some hidden connection between the biological functions which TBP-2 participates in and some distinct diseases. This review presents only a summary of the roles that TBP-2 plays in cancer, DM, cataracts, and so on, as well as its universal mechanisms. Further investigations are needed for the cell signaling pathways of the effects caused by TBP-2. A greater understanding of the mechanisms of TBP-2 could produce potential new targets for the treatment of diseases, including cancer and diabetes, cardiovascular disease, and cataracts.

Morphologic Patterns Formed by the Anomalous Fibers Occurring Along the Anterior Capsule of the Crystalline Lens in People With the Long Anterior Zonule Trait.

People with the long anterior zonule (LAZ) trait, which may have prevalence near 2%, have zonular fibers that extend more central than usual along the anterior capsule of the crystalline lens. The anomalous fibers can be observed in vivo with clinical slit lamp biomicroscopy after pharmacologic pupil dilation, and although minimally studied, the LAZ trait may have importance to glaucoma, retinal degeneration, and cataract surgery. To further characterize LAZ morphology, a custom computer program was used to trace LAZ fibers seen on retro-illumination photos acquired during previous study at an academic, urban eye care facility in Chicago, IL. There were 59 African-Americans (54 female; median age = 70 years, 53-91 years) included in the analysis. After initial review of the zonule tracings, we identified three basic LAZ patterns. We called one pattern (47% of right eyes) a "non-segmental LAZ pattern," which was predominated by fibers that could be visually traced to the dilated pupil border where they became obscured by the iris. Another pattern (35% of right eyes), the "segmental LAZ pattern," was predominated by fibers that appeared to terminate abruptly without detectable extension to the pupil border. The third pattern (18% of right eyes), the "mixed LAZ pattern," had a more equivalent mixture of the other two fiber morphologies. Compared to the "non-segmental" group, the "segmental" LAZ eyes had smaller central zonule-free zones (P < 0.0001), and they tended to exhibit fewer LAZ fibers (P = 0.07). These data improve understanding of LAZ clinical anatomy and may be helpful to future investigation. Anat Rec, 300:1336-1347, 2017. © 2017 Wiley Periodicals, Inc.

The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species.

PURPOSE: The purpose of this study was to determine in which species and under what conditions lens tumors occur. DESIGN: A review of databases of available human and veterinary ocular pathologic material and the previously reported literature. PARTICIPANTS: Approximately 18 000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health between 1920 and 2014 and 45 000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin between 1983 and 2014. METHODS: Material in 2 major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as a new growth of tissue characterized by progressive, uncontrolled proliferation of cells. In addition, cases presented at 3 major eye pathologic societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the institutional review board to carry out this study was obtained. MAIN OUTCOME MEASURES: The presence of tumors of the lens. RESULTS: The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. In the veterinary school database, 4.5% of feline intraocular and adnexal neoplasms (234/5153) were designated as feline ocular posttraumatic sarcoma, a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All 4 species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. CONCLUSIONS: Our results suggest that lens tumors do not occur in humans. In contrast, after lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists that prevents lens tumors in humans.

Bilateral lens luxation and intracapsular lens extractions in a Matshchie's tree kangaroo.

An adult, female, captive, Matshchie's tree kangaroo was diagnosed with an anterior lens luxation in the right eye and a lens subluxation in the left eye. Both eyes were treated surgically with intracapsular lens extractions. A 360° rhegmatogenous retinal detachment was diagnosed 6 months postoperatively in the left eye. Aphakic vision was maintained in the right eye 9 months postoperatively. Based on family history and the lack of antecedent ocular disease, the lens luxations were presumed to be inherited and veterinarians should be aware of this condition within the captive tree kangaroo population.

Bilateral anterior lenticonus in a case of Alport syndrome: a clinical and histopathological correlation after successful clear lens extraction.

A 29-year-old woman presented with symptoms of gradual, progressive, painless diminution of vision in both eyes for past 8-10 years. On examination, uncorrected visual acuity was 20/60 in the right eye and 20/126 in the left eye. Anterior segment examination was essentially normal except for a conical protrusion in the pupillary axis of the anterior lens capsule with a clear underlying lens. During surgery, central protruded fragile lens capsule was meticulously handled to create well-centered continuous curvilinear capsulorhexis by using paediatric rhexis forceps. Histopathology of excised capsule showed markedly thinned lens capsule with normal epithelium. Electron microscopy of the anterior lens capsule showed multiple linear and irregular zones of dehiscence. Few of these had fibrillar, irregular electron-dense material and vacuoles; and adjacent cells were irregular suggestive of Alport syndrome. Postoperative course was uneventful and visual acuity improved to 20/20 unaided. Clear lens extraction is an effective means of rehabilitating visually symptomatic anterior lenticonus of Alport syndrome.

Intraocular sarcoma associated with a rupture lens in a rabbit (Oryctolagus cuniculus).

This case report describes the clinical manifestations and ocular pathology of an intraocular sarcoma in a spayed female 7-year-old rabbit that developed clinical signs consistent with phacoclastic uveitis at 6 months of age, which was left untreated for most of the next 6 years. Ophthalmologic examination confirmed pupillary occlusion, aqueous flare, fibrin, and lens debris within the anterior chamber of the right eye. The right eye was blind and phthisical. The tentative clinical diagnosis was chronic phacoclastic uveitis, and a routine transconjunctival enucleation of the right eye was completed. The globe was formalin-fixed and submitted for histologic examination. Light microscopic examination revealed a ruptured cataractous lens, uveitis, retinal detachment, and an intraocular sarcoma centered around the lens. Immunohistochemical (IHC) staining was positive for smooth muscle actin and vimentin and negative for Desmin and cytokeratin intermediate filaments.