[Corneal dystrophy (CD)-induced pain and visual impairment in childhood].

Many forms of the 25 corneal dystrophies (CD) manifest already in childhood with bilateral corneal opacities without any visual impairment in most cases. Pain attacks due to recurrent erosion with red eye and epiphora can occur in combination with the first dystrophy-specific corneal opacities, e.g.

Serine protease HtrA1 accumulates in corneal transforming growth factor beta induced protein (TGFBIp) amyloid deposits.

Purpose: Specific mutations in the transforming growth factor beta induced (TGFBI) gene are associated with lattice corneal dystrophy (LCD) type 1 and its variants. In this study, we performed an in-depth proteomic analysis of human corneal amyloid deposits associated with the heterozygous A546D mutation in TGFBI.

Methods: Corneal amyloid deposits and the surrounding corneal stroma were procured by laser capture microdissection from a patient with an A546D mutation in TGFBI.

Calpains, cleaved mini-dysferlinC72, and L-type channels underpin calcium-dependent muscle membrane repair.

Dysferlin is proposed as a key mediator of calcium-dependent muscle membrane repair, although its precise role has remained elusive. Dysferlin interacts with a new membrane repair protein, mitsugumin 53 (MG53), an E3 ubiquitin ligase that shows rapid recruitment to injury sites. Using a novel ballistics assay in primary human myotubes, we show it is not full-length dysferlin recruited to sites of membrane injury but an injury-specific calpain-cleavage product, mini-dysferlinC72.

Features of recurrence after excimer laser phototherapeutic keratectomy for anterior corneal pathologies in North China.

Purpose: To study long-term clinical patterns of recurrence of anterior corneal pathologies after excimer laser phototherapeutic keratectomy (PTK).

Design: Retrospective, noncomparative, interventional case series.

Participants: Thirty patients (44 eyes) with anterior corneal pathologies who underwent PTK and experienced recurrence after long-term follow-up between March 1997 and April 2012.

Lattice Corneal Dystrophy-Variant: a report of three new cases due to p.V631D mutation in the TGFBI gene.

Purpose: To report clinical findings and molecular defect in three subjects affected by Biber-Haab-Dimmer dystrophy or Lattice Corneal Dystrophy Type I (LCD1), a corneal dystrophy transmitted as an autosomal dominant tract.

Materials And Methods: Three subjects underwent a complete ophthalmic examination and confocal microscopy study. Following the collection of DNA from the patients, the TGFBI gene was screened for mutations by direct sequencing.

Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy.

Objective: To investigate whether sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy (FSHD).

Methods: Sarcomeric function was evaluated by contractile studies on demembranated single muscle fibers obtained from quadriceps muscle biopsies of 4 patients with FSHD and 4 healthy controls. The sarcomere length dependency of force was determined together with measurements of thin filament length using immunofluorescence confocal scanning laser microscopy.

PROSE therapy used to minimize corneal trauma in patients with corneal epithelial defects.

Purpose: To review the effectiveness of continuous or extended daily wear of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for treating recurrent or persistent corneal epithelial defects from a variety of causes that were refractory to conventional therapy in 9 patients.

Design: Retrospective case series.

Methods: The medical records of 9 patients with a history of recurrent or persistent corneal epithelial defects resistant to conventional medical treatment who received treatment at the Cullen Eye Institute between January 2011 and July 2012 were reviewed.

Absence of beta-amyloid in cortical cataracts of donors with and without Alzheimer's disease.

Eye lenses from human donors with and without Alzheimer's disease (AD) were studied to evaluate the presence of amyloid in cortical cataract. We obtained 39 lenses from 21 postmortem donors with AD and 15 lenses from age-matched controls provided by the Banco de Ojos para Tratamientos de la Ceguera (Barcelona, Spain). For 17 donors, AD was clinically diagnosed by general physicians and for 4 donors the AD diagnosis was neuropathologically confirmed.

Changes of clinical manifestation of granular corneal deposits because of recurrent corneal erosion in granular corneal dystrophy types 1 and 2.

Purpose: To elucidate changes of clinical manifestation of granular corneal deposits after recurrent corneal erosion in granular corneal dystrophy types 1 and 2 (GCD1 and GCD2).

Methods: Six patients (5 patients with GCD2 and 1 with GCD1) were included. Slit-lamp photographs of all patients and Fourier domain optical coherence tomography images of 3 available patients were analyzed.

Polymorphic fibrillation of the destabilized fourth fasciclin-1 domain mutant A546T of the Transforming growth factor-β-induced protein (TGFBIp) occurs through multiple pathways with different oligomeric intermediates.

Mutations in the transforming growth factor β-induced protein (TGFBIp) are linked to the development of corneal dystrophies in which abnormal protein deposition in the cornea leads to a loss of corneal transparency and ultimately blindness. Different mutations give rise to phenotypically distinct corneal dystrophies. Most mutations are located in the fourth fasciclin-1 domain (FAS1-4).

TGFBI gene mutations in a Korean population with corneal dystrophy.

Purpose: To investigate the clinical and genetic features of Korean patients with corneal dystrophies associated with mutations in the human transforming growth factor-β-induced (TGFBI) gene.

Methods: In this study, 387 subjects (71 families and 89 individuals - 268 patients having TGFBI corneal dystrophies and 119 normal relatives) were assessed. All subjects underwent a complete ophthalmologic evaluation, including biomicroscopic inspection and dilated fundus examination.

Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 are strongly expressed in the epithelium of human granular and lattice type I corneal dystrophies.

Purpose: To determine the extracellular matrix proteins involved in the formation of human granular and lattice type I corneal stromal dystrophies, the expression patterns of fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were compared in human corneal stromal dystrophy samples.

Methods: Ten cases of granular dystrophy, 7 cases of lattice dystrophy, and 6 normal corneal buttons collected during corneal transplantation were examined for their expression patterns of fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 by immunohistochemistry.

Results: Highly elevated fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 were observed in the epithelial layer of both granular and lattice type I dystrophies.

In vitro amyloid aggregate forming ability of TGFBI mutants that cause corneal dystrophies.

Purpose: We investigated the in vitro amyloid aggregation ability of TGFBI (transforming growth factor beta-induced) mutants causing corneal dystrophies (CDs).

Methods: Peripheral blood samples were collected from 42 unrelated Chinese CD patients and 185 healthy subjects for mutation screening in all TGFBI coding exons and flanking introns. The expression vector pCMV6_TGFBI containing wild-type, Arg-124, or Arg-555 mutations was transfected to HEK293 cells.

Deep anterior lamellar keratoplasty for the treatment of stromal corneal dystrophies.

Purpose: To report the perioperative complications and clinical outcomes after deep anterior lamellar keratoplasty (DALK) using the big bubble technique in eyes with stromal corneal dystrophies.

Patients And Methods: Seventy-four eyes of 65 patients who underwent DALK for stromal corneal dystrophies were evaluated in this retrospective interventional case series study. Main outcome measures were intraoperative and postoperative complications, postoperative uncorrected visual acuity, best spectacle-corrected visual acuity, spherical equivalent refraction, and topographic astigmatism.

TGFBI and CHST6 gene analysis in Chinese stromal corneal dystrophies.

Aim: To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies (CD) in 8 Chinese probands.

Methods: Eight unrelated patients with stromal corneal dystrophies were recruited in this study; all affected members were assessed by completely ophthalmologic examinations. Genomic DNA was extracted from peripheral leukocytes, 17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction (PCR), sequenced directly and compared with the reference database.

Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type.

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systematic amyloidosis characterized by lattice corneal dystrophy, cranial neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish population, FAF is a considerably rare disorder in other regions. In this study, we examined the clinical characteristics as well as the haplotypes of six Japanese patients with FAF from five families.

Investigation of the influence of Arg555Trp and Thr538Pro TGFBI mutations on C-terminal cleavage and cell endoplasmic reticulum stress.

Purpose: To gain insight into the mechanisms underlying the transforming growth factor-beta induced (TGFBI)-related corneal dystrophies and the influence of the Arg555Trp and Thr538Pro, TGFBI mutations on C-terminal cleavage and cell endoplasmic reticulum (ER) stress were investigated.

Methods: The Arg555Trp and Thr538Pro mutations known to be associated with corneal dystrophy granular type I and lattice corneal dystrophy, respectively, were introduced with the two-sequential PCR site-directed mutagenesis technique. Wild-type and mutant TGFBI DNAs were cloned into the pcDNA3.

Familial amyloidotic polyneuropathy type IV--gelsolin amyloidosis.

Familial amyloidotic polyneuropathy type IV, or Gelsolin amyloidosis (GA), is a rare condition caused by G654A or G654T mutation in gelsolin gene at 9q32-34. Gelsolin seems essential in many processes, including inflammation, cell motility, neural recovery, apoptosis and even carcinogenesis. So far reported from many European countries, USA, Japan, Iran and Brazil, GA is probably still underdiagnosed.

Long-term risk of intraocular pressure elevation and glaucoma escalation after deep anterior lamellar keratoplasty.

Background: To determine the prevalence and severity of intraocular pressure changes after deep anterior lamellar keratoplasty and its effect on visual function.

Design: Retrospective cohort study.

Participants: All patients undergoing deep anterior lamellar keratoplasty procedures at a tertiary referral centre (Leeds University Hospitals, UK) using a manual dissection technique.

Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention.

Protein misassembly into aggregate structures, including cross-β-sheet amyloid fibrils, is linked to diseases characterized by the degeneration of post-mitotic tissue. While amyloid fibril deposition in the extracellular space certainly disrupts cellular and tissue architecture late in the course of amyloid diseases, strong genetic, pathological and pharmacologic evidence suggests that the process of amyloid fibril formation itself, known as amyloidogenesis, likely causes these maladies. It seems that the formation of oligomeric aggregates during the amyloidogenesis process causes the proteotoxicity and cytotoxicity characteristic of these disorders.

Phenotype-genotype correlations in patients with TGFBI-linked corneal dystrophies in Taiwan.

Purpose: To determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-β-induced (TGFBI) mutations at the National Taiwan University Hospital.

Methods: Twenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations.

Composition and proteolytic processing of corneal deposits associated with mutations in the TGFBI gene.

Different types of granular corneal dystrophy (GCD) and lattice corneal dystrophy (LCD) are associated with mutations in the transforming growth factor beta induced gene (TGFBI). These dystrophies are characterized by the formation of non-amyloid granular deposits (GCDs) and amyloid (LCD type 1 and its variants) in the cornea. Typical corneal non-amyloid deposits from GCD type 2 (R124H), amyloid from a variant of LCD type 1 (V624M) and disease-free tissue controls were procured by laser capture microdissection and analyzed by tandem mass spectrometry.