Fibrotic remodeling and tissue regeneration mechanisms define the therapeutic potential of human muscular progenitors.

Fibrosis is an intrinsic biological reaction toward the challenges of tissue injury that is implicated in the wound-healing process. Although it is useful to efficiently mitigate the damage, progression of fibrosis is responsible for the morbidity and mortality occurring in a variety of diseases. Because of lacking effective treatments, there is an emerging need for exploring antifibrotic strategies. Cell therapy based on stem/progenitor cells is regarded as a promising approach for treating fibrotic diseases. Appropriate selection of cellular sources is required for beneficial results. Muscle precursor cells (MPCs) are specialized progenitors harvested from skeletal muscle for conducting muscle regeneration. Whether they are also effective in regulating fibrosis has seldom been explored and merits further investigation. MPCs were successfully harvested from all human samples regardless of demographic backgrounds. The extracellular matrices remodeling was enhanced through the paracrine effects mediated by MPCs. The suppression effects on fibrosis were confirmed in vivo when MPCs were transplanted into the diseased animals with oral submucous fibrosis. The data shown here revealed the potential of MPCs to be employed to simultaneously regulate both processes of fibrosis and tissue regeneration, supporting them as the promising cell candidates for development of the cell therapy for antifibrosis and tissue regeneration.

Necessity of Local Modification for Deep Learning Algorithms to Predict Diabetic Retinopathy.

Deep learning (DL) algorithms are used to diagnose diabetic retinopathy (DR). However, most of these algorithms have been trained using global data or data from patients of a single region. Using different model architectures (e.g., Inception-v3, ResNet101, and DenseNet121), we assessed the necessity of modifying the algorithms for universal society screening. We used the open-source dataset from the Kaggle Diabetic Retinopathy Detection competition to develop a model for the detection of DR severity. We used a local dataset from Taipei City Hospital to verify the necessity of model localization and validated the three aforementioned models with local datasets. The experimental results revealed that Inception-v3 outperformed ResNet101 and DenseNet121 with a foreign global dataset, whereas DenseNet121 outperformed Inception-v3 and ResNet101 with the local dataset. The quadratic weighted kappa score (κ) was used to evaluate the model performance. All models had 5-8% higher κ for the local dataset than for the foreign dataset. Confusion matrix analysis revealed that, compared with the local ophthalmologists' diagnoses, the severity predicted by the three models was overestimated. Thus, DL algorithms using artificial intelligence based on global data must be locally modified to ensure the applicability of a well-trained model to make diagnoses in clinical environments.

Protective behaviours of near work and time outdoors in myopia prevalence and progression in myopic children: a 2-year prospective population study.

AIM: To investigate the protective behaviours of longer near work distance, discontinuing near work and more time outdoors in recess from parent self-report in the myopia prevalence and progression among myopic children aged 9-11 years. METHODS: Myopia Investigation study in Taipei is a longitudinal population-based study that enrolled elementary school students in Taipei. We provided vision and refraction examination every 6 months. Spherical equivalent (SE) of cycloplegic refraction ≤-0.50 Diopter (D) is defined as myopia. Total 10 743 (70.4%) students completed 2-year refraction data and questionnaire. The myopia prevalence and progression (difference of SE) in baseline, 6, 12, 18 and 24 months were compared by generalised estimating equations. RESULTS: Children with persistent protective behaviour had significant lower prevalence of myopia. The protective impact was statistically significant from 6 to 24 months. In 2 years follow-up, risk ratio after adjusting the background variables and the other two behaviours in near work distance, near work time and outdoor time were 0.71, 0.89 and 0.77. In SE analysis, after adjusting the other two behaviours, near work distance >30 cm (-0.7 vs -1.04 D; p<0.001), discontinuing near work every 30 min (-0.77 vs -0.96 D, p=0.005) and more time outdoors in recess from parent self-report (-0.75 vs -0.98 D; p=0.012) revealed protective impacts on diminishing myopia progression from 6 to 24 months. CONCLUSION: In myopic children aged around 10 years in Taipei, longer distance in near work, discontinuing near work every 30 min and more outdoor time from parent self-report are protective behaviours in myopia prevalence and progression in 6-24 months.

Correction: Maintenance of the spheroid organization and properties of glandular progenitor cells by fabricated chitosan based biomaterials.

Correction for 'Maintenance of the spheroid organization and properties of glandular progenitor cells by fabricated chitosan based biomaterials' by Hao-Wei Lee et al., Biomater. Sci., 2018, DOI: 10.1039/c7bm00559h.

Maintenance of the spheroid organization and properties of glandular progenitor cells by fabricated chitosan based biomaterials.

Dysfunctional salivary gland (SG) is an unsolved clinical challenge, which is presented as xerostomia. Cell therapy is a promising treatment for restoring SG function. Salispheres are spheroid cellular organizations derived from SG stem cells. Benefitting from these cellular organizations, SG stem cells can be expanded to regenerate SG. During in vitro culture, the spontaneous reorganization of salispheres may change the features of residing SG stem cells. Therefore, it is imperative to explore ways to maintain the spheroid structure of salispheres during cell expansion in vitro. Herein, we explored biomaterial approaches using chitosan. Chitosan based biomaterials were fabricated in different forms to offer distinct interactive surfaces for cultured salispheres. The number and size of the salispheres increase in the chitosan-containing systems without increasing the incidence of spheroid cavitation. The effect of chitosan increases with high chitosan concentrations, which is optimum when chitosan is fabricated in a soluble form. The chitosan effect contributes to the regulation of the intercellular interactions and polarization within the spheroid structures. By retarding the process of salisphere cavitation, chitosan preserves the features of salivary gland progenitor cells in the cultured salispheres. The results suggest that the chitosan-containing system could effectively maintain the primitive structures and properties of salispheres during in vitro expansion, which demonstrates the potential application of salispheres for cell therapy of dysfunctional SG.

Intraocular pressure monitoring by rebound tonometry in children with myopia.

BACKGROUND/PURPOSE: Topical atropine treatment is generally accepted to retard the progression of myopia, but it is associated with side effects such as photophobia and elevation of intraocular pressure (IOP). IOP measurements in children are challenging. The traditional applanation tonometry by direct contact with the cornea will require patient's cooperation. The rebound tonometer, using a dynamic electromechanical method for measuring IOP, shows good correlation with traditional tonometry. The purpose of this study is to evaluate the IOP of myopic children under atropine treatment using rebound tonometer and to compare the characteristics between rebound tonometry and applanation tonometry. METHODS: This study is a prospective study measuring IOP by rebound tonometer in myopic children under regular low-dose atropine treatment. We recruited children with refraction error showing myopia over -0.5 D with 0.15%, 0.3%, or 0.5% atropine eye drops use every night or every other night for myopia control. Children with treatment duration of atropine <1 month were excluded from the study. IOP measurements were performed by applanation tonometer (Tono-Pen XL, Reichert) and rebound tonometer (ICARE). The reliability of rebound tonometer was analyzed with percentage. Comparison of IOP between rebound tonometer and applanation tonometry was presented. RESULTS: The rebound tonometry was well tolerated by all participants and caused no complaints, discomfort, or adverse events. Totally 42 myopic eyes of 42 subjects were included in the study. The average age of these participants was 10 years old, range from 5 to 16. Median = 10 years old. The average IOP of the right eye by rebound tonometer was 17.4 ± 3 mmHg, and 17.1 ± 3 mmHg by applanation tonometry. Nearly 19%, 33%, and 24% of difference of IOP readings between rebound tonometer and Tono-Pen applanation are within 0 mmHg, 1 mmHg, and 1-2 mmHg, respectively. CONCLUSIONS: Rebound tonometry has good correlation with applanation tonometry and 76.1% of differences between two tonometers are <2 mmHg. The advantage of drop-free rebound tonometry has made it easier to obtain IOP readings in myopia children under atropine treatment.

Regulating temporospatial dynamics of morphogen for structure formation of the lacrimal gland by chitosan biomaterials.

The lacrimal gland is an important organ responsible for regulating tear synthesis and secretion. The major work of lacrimal gland (LG) is to lubricate the ocular surface and maintain the health of eyes. Functional deterioration of the lacrimal gland happens because of aging, diseases, or therapeutic complications, but without effective treatments till now. The LG originates from the epithelium of ocular surface and develops by branching morphogenesis. To regenerate functional LGs, it is required to explore the way of recapitulating and facilitating the organ to establish the intricate and ramified structure. In this study, we proposed an approach using chitosan biomaterials to create a biomimetic environment beneficial to the branching structure formation of developing LG. The morphogenetic effect of chitosan was specific and optimized to promote LG branching. With chitosan, increase in temporal expression and local concentration of endogenous HGF-related molecules creates an environment around the emerging tip of LG epithelia. By efficiently enhancing downstream signaling of HGF pathways, the cellular activities and behaviors were activated to contribute to LG branching morphogenesis. The morphogenetic effect of chitosan was abolished by either ligand or receptor deprivation, or inhibition of downstream signaling transduction. Our results elucidated the underlying mechanism accounting for chitosan morphogenetic effects on LG, and also proposed promising approaches with chitosan to assist tissue structure formation of the LG.

Data supporting regulating temporospatial dynamics of morphogen for structure formation of the lacrimal gland by chitosan biomaterials.

The lacrimal gland is responsible for tear synthesis and secretion, and is derived from the epithelia of ocular surface and generated by branching morphogenesis. The dataset presented in this article is to support the research results of the effect of chitosan biomaterials on facilitating the structure formation of the lacrimal gland by regulating temporospatial dynamics of morphogen. The embryonic lacrimal gland explants were used as the standard experimental model for investigating lacrimal gland branching morphogenesis. Chitosan biomaterials promoted lacrimal gland branching with a dose-dependent effect. It helped in vivo binding of hepatocyte growth factor (HGF) related molecules in the epithelial-mesenchymal boundary of emerging epithelial branches. When mitogen-activated protein kinase (MAPK) or protein kinase B (Akt/PKB) inhibitors applied, the chitosan effects reduced. Nonetheless, the ratios of MAPK and Akt/PKB phosphorylation were still greater in the chitosan group than the control. The data demonstrated here confirm the essential role of HGF-signaling in chitosan-promoted structure formation of the lacrimal gland.

Data supporting chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components.

To investigate the role of basement membrane (BM) in chitosan-mediated morphogenesis of the salivary glands, the embryonic submandibular gland (SMG) experimental model was used. Chitosan promotes branching at distinct stages in SMG morphogenesis. When enzymes such as type IV collagenase, dispase, and cathepsin B were used to digest the BM components, the morphogenetic effect mediated by chitosan disappeared. Immunofluorescence revealed that the corresponding receptors for BM components, including CD49c, CD49f, CD29, and dystroglycan, were locally enriched at the epithelial-mesenchymal junction around BM areas. The functional roles of laminin α1 and α5 in SMG branching were explored via siRNA knockdown, and suppression was confirmed at both the RNA and protein levels (Yang and Hsiao, Biomaterials, http://dx.doi.org/10.1016/j.biomaterials.2015.06.028, 2015). This data article demonstrates the experimental approaches to investigate the role of basement membrane in the structure formation of the salivary gland engineered by biomaterials.

Chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components.

Tissue structure is important for inherent physiological function and should be recapitulated during tissue engineering for regenerative purposes. The salivary gland is a branched organ that is responsible for saliva secretion and regulation. The salivary glands develop from epithelial-mesenchymal interactions, and depend on the support of the basement membrane (BM). Chitosan-based biomaterials have been demonstrated to be competent in facilitating the formation of salivary gland tissue structure. However, the underlying mechanisms have remained elusive. In the developing submandibular gland (SMG), the chitosan effect was found to diminish when collagen and laminin were removed from cultured SMG explants. Chitosan increased the expression of BM components including collagen, laminin, and heparan sulfate proteoglycan, and also facilitated BM components and the corresponding receptors to be expressed in tissue-specific patterns beneficial for SMG branching. The chitosan effect decreased when either laminin components or receptors were inhibited, as well when the downstream signaling was blocked. Our results revealed that chitosan promotes salivary glands branching through the BM. By regulating BM components and receptors, chitosan efficiently stimulated downstream signaling to facilitate salivary gland branching. The present study revealed the underlying mechanism of the chitosan effect in engineering SMG structure formation.

Controlling branching structure formation of the salivary gland by the degree of chitosan deacetylation.

The salivary gland is characterized by ramified epithelial branches, a specific tissue structure responsible for saliva production and regulation. To regenerate the salivary gland function, it is important to establish the tissue structure. Chitosan is a deacetylated derivative of chitin with wide biomedical applications. Because of its deacetylated nature, chitosan has different properties when prepared with different degrees of deacetylation (DDA). However, the impact of chitosan DDA on the effect of regulating tissue structure formation remains unexplored. In this study, the embryonic murine submandibular gland (SMG) was used as a model to investigate the role of chitosan DDA in regulating tissue structure formation of the salivary gland. When chitin substrates with different DDA were used, the branching numbers of cultured SMG explants changed. Similar effects were observed in the culture with chitosan prepared using different degrees of acetylation. The mRNA expressions of type I and type III collagen were elevated in SMG explants with enhanced branching morphogenesis, as was the protein level. In addition to the amounts of collagen, type I and type III collagen fibers were spatially present in the epithelial-mesenchymal junction of developing branches in the culture with chitosan of a specific range of DDA. The branch-promoting effect of chitosan DDA was abolished when SMG explants were treated with collagenase, both early in the stage of branch initiation and with the establishment of the branching structure. The branch-promoting effect of chitosan DDA disappeared when antisense oligonucleotides were applied to specifically block type III collagen. This study demonstrates for the first time that DDA of chitosan affects tissue structure formation. The different proportions of side-chain components of chitin derivatives regulate structural formation of cultured SMG, indicating that DDA is an important parameter using chitosan as a biomaterial for tissue structure formation of the salivary glands.

Diagnosis of microsporidial keratitis with in vivo confocal microscopy.

As a rare cause of microbial keratitis, microsporidial keratitis (MK) is first described in a patient with acquired immunodeficiency syndrome. As increased use of topical steroid creates a localized immunosuppressive environment of the eyes, MK occurs more commonly than expected in immunocompetent patients nowadays. Owing to initial insidious growth of pathogens and nonspecific ocular symptoms of infected patients, its frequent misdiagnosis has posed a major clinical challenge in recent decades. Without appropriate treatments, MK can progress deeply into corneal stroma, anterior and posterior segments, subsequently deteriorating vision severely and ultimately requiring corneal transplant. Related risk factors for the occurrence of MK in immunocompetent individuals include contact lens wear, topical steroid use, previous corneal trauma, and a history of laser refractive surgery. The conventional standard of MK diagnosis is based on a tissue biopsy by superficial corneal scrapping. In vivo confocal laser scanning microscopy can obtain images through the cornea in a plane paralleling to the vertical axis. This approach provides an effective method of identifying tissue layers that correspond to corneal histologic structures. This current study investigates the efficacy of \textit{in vivo} confocal laser scanning microscopy in diagnosing MK in immunocompetent patients. The clinical presentations of enrolled patients, including features of slit lamp biomicroscopy and the histopathological results of corneal scrapping, were described. In these patients, the confocal microscopy identified multiple small intracellular hyper-reflective dots in the cytoplasm of corneal epithelial cells and stromal keratocytes. Additionally, the confocal microscopic images clearly revealed the enhanced cytoplasm of cell with intracellular round hyper-reflective dots. The size and morphology of hyper-reflective dots were compatible with the spores of microsporidia found in corneal tissue. Moreover, vision recovered after topical use of antimicrobial medicine. This observation suggests that in vivo confocal laser scanning microscopy provides a rapid, non-invasive, and high resolution scheme for diagnosing MK. In addition to diminishing the risk of secondary infection from epithelial defect created by superficial debridement, this approach facilitates early diagnosis and appropriate treatments. Furthermore, from a series of images taken during the clinical courses, this method is highly promising for use in monitoring treatment effects and identifying the recurrence of MK.

Chitosan biomaterials induce branching morphogenesis in a model of tissue-engineered glandular organs in serum-free conditions.

Glandular organs feature ramified structures that are important for regulating physiological transport. The aim of this study was to develop a biomaterial-assisted, serum-free culture system to generate branching structures in explants of glandular organs. The fetal mammary gland (MG) was selected as the model organ to study the formation of glandular structure. Among the many biomaterials tested, chitosan demonstrated a superior effect in promoting branch formation in MGs. The morphogenetic effect toward MG branching was chitosan specific and not observed with other analogs with similar chemical compositions or structures. The molecular weight and specific linkages in the chitosan polymer were important parameters in mediating the morphogenetic effect. MG explants from different anatomical locations effectively promoted structure formation. Blocking endogenous fibroblast growth factor 10 (FGF10) inhibited the morphogenetic effect of chitosan, indicating that the chitosan effect was FGF10 dependent. This work demonstrates the feasibility of creating a serum-free system that is competent in facilitating tissue morphogenesis in MG. MG tissue structure can be efficiently generated in a biocompatible system, which was assisted by biomaterials.

Home assessment of diurnal intraocular pressure in healthy children using the Icare rebound tonometer.

BACKGROUND: Although intraocular pressure (IOP) is known to vary with the circadian cycle in nonglaucomatous and glaucomatous eyes of adults, the clinical assessment of IOP often relies on periodic measurements obtained at office visits during daytime hours. Little has been reported on diurnal IOP patterns in healthy children. The purpose of this study was to evaluate diurnal IOP in normal eyes of healthy children with the Icare rebound tonometer and when recorded by a parent at home. METHODS: This was a prospective study of IOP in normal eyes of healthy children. Children were recruited from a pediatric eye clinic. A parent was instructed on the use of the Icare rebound tonometer by a study physician and demonstrated proficiency its use in the clinic, at which time a masked IOP reading was also made with Goldmann applanation by a different study clinician. Home IOPs were then obtained and recorded 6 times daily at 2- to 3-hours intervals during 2 consecutive days by a parent. RESULTS: A total of 22 normal eyes (of 11 children) were included. We found that children without glaucoma demonstrate mean diurnal IOP fluctuation of 4-6 mm Hg, with similar IOP between right and left eyes, fair repeatability between consecutive days, and a tendency for higher early morning and lower late evening IOP. CONCLUSIONS: Healthy children without glaucoma demonstrate some diurnal fluctuation in IOP, comparable with that reported in nonglaucomatous eyes of adults. This information should prove as comparative for assessment of IOP fluctuation in children with known or suspected glaucoma.

An alternative way to think about glaucoma screening, using a questionnaire as a tool, Chinese version.

RATIONALE, AIMS AND OBJECTIVES: To develop a short screening test for the detection of preclinical glaucoma. METHOD: This case-control study involved 690 participants aged 40 years or older: 338 patients with glaucoma or suspected glaucoma and 352 patients without glaucoma, who served as a control group. All participants were interviewed by a single trained research assistant. Patients' basic demographic and clinical information, past ophthalmic history and responses on the National Eye Institute 25-item Visual Function Questionnaire were collected. Two glaucoma-trained ophthalmologists examined all the participants using standard procedures to make a diagnosis. The biostatistical differences between the two groups were determined. RESULTS: Five items were selected for glaucoma screening: 'Sense of worse vision compared with those of the same age', 'Ocular pain or discomfort during the past 6 months', 'History of cataract', 'Family history of glaucoma' and 'Hyperopia'. A score of 2 or more was used to define a group of positive cases with the most appropriate values for sensitivity (79.0%), specificity (76.7%) and predictive power (a positive predictive value of 76.5% and a negative predictive value of 79.2%). CONCLUSION: A five-item instrument was developed to detect preclinical glaucoma. Anyone with a score of 2 or more may need further ophthalmic examination and treatment.

Home tonometry for management of pediatric glaucoma.

PURPOSE: To use iCare rebound tonometry in the home setting for documentation of diurnal intraocular pressure (IOP) fluctuations in children. DESIGN: Nonrandomized, prospective clinical study. METHODS: Pediatric ophthalmology clinic patients were recruited between October 2009 and February 2010 who were able to cooperate with IOP measurement by iCare rebound tonometry and whose caregiver was willing and able to obtain iCare measurements at home. The child's IOP was measured first by iCare tonometry followed by a second method (Goldmann applanation [GAT]). The caregiver was instructed on the use of the iCare tonometer. The subject's IOP was measured by the caregiver at home at designated time periods for at least 2 consecutive days. RESULTS: Seventeen children (17 eyes) with known or suspected glaucoma and 11 normal children were included. Excellent reliability was obtained by caregivers in 70% of iCare measurements. Mean difference between iCare and GAT in clinic was 2.0 ± 4.0 mm Hg, P = .08. Daily IOP fluctuation occurred in both subjects with glaucoma and normal subjects. In children with known or suspected glaucoma, relative peak and trough IOPs occurred in the early morning (45%) and late evening (43.5%), respectively. Comparison of the peak IOP measured at home vs in the clinic was >6 mm Hg in 5 of 16 subjects (31%) and affected glaucoma management in several subjects. CONCLUSIONS: In selected children with glaucoma, home tonometry by iCare rebound tonometry was reliable, easily performed by caregivers, and well tolerated, and offered IOP information valuable in clinical management.

Icare rebound tonometry in children with known and suspected glaucoma.

BACKGROUND: Accurate intraocular pressure (IOP) measurement, important in managing pediatric glaucoma, often presents challenges. The Icare rebound tonometer shows promise for screening healthy children and has been reported comparable with Goldmann applanation in adults with glaucoma. The purpose of this study was to evaluate the Icare tonometer against Goldmann applanation for clinic IOP measurement in pediatric glaucoma. METHODS: This was a prospective study comparing Icare versus Goldmann tonometry in pediatric glaucoma. Children with known or suspected glaucoma were recruited from scheduled clinic visits. IOP was measured with the Icare tonometer by a clinician and subsequently measured with Goldmann applanation tonometry (GAT) by a different single masked clinician. RESULTS: A total of 71 eyes of 71 children with known or suspected glaucoma were included. IOP by GAT ranged from 9 to 36 mm Hg. Icare readings ranged from 11 to 44 mm Hg. Mean difference between Icare and GAT was 2.3 ± SD 3.7 mm Hg, p < 0.0001. Icare IOPs were within ± 3 mm Hg of GAT in 63%. Icare IOPs were ≥GAT IOPs in 75%. The following factors were not associated with Icare IOPs greater than GAT: child's age, glaucoma diagnosis, strabismus, nystagmus, central corneal thickness, Icare instrument-reported reliability, number of glaucoma surgeries or medications, corneal abnormalities, and visual acuity. CONCLUSIONS: IOP by Icare tonometry was within 3 mm Hg of IOP by GAT in 63% and greater than GAT in 75%. This device may be reasonable to estimate IOP in selected children with known or suspected glaucoma whose IOP cannot otherwise be obtained in clinic; however, correlation of Icare IOPs with clinical findings must continue to be considered in each case.

The impact of compositional topography of amniotic membrane scaffold on tissue morphogenesis of salivary gland.

Amniotic membrane (AM) has been widely used in the reconstruction of oral epithelial defects. However, whether it is also effective in facilitating tissue formation of salivary gland, an appendix of oral epithelia, has never been explored. To investigate the effects and the underlying mechanism of AM on salivary gland morphogenesis, murine fetal submandibular gland (SMG) explants were cultured on different preparations of AM scaffolds. It was found that, on AM stromal scaffold, SMG demonstrated well-developed branching morphogenesis. Nonetheless, on AM epithelial scaffold, SMG epithelial cell converted to a spindle-shape, lost intercellular connection, changed cytoskeletal organization, and exhibited scattering behaviors. Meanwhile, the integrity of SMG basement membrane was dismantled as well. However, when acellular AM epithelial scaffold was used, cultured SMG demonstrated organized morphology, indicating that AM epithelial component provided specific surface features for SMG morphogenesis. To further investigate AM scaffold morphogenetic effect, it was found hepatocyte growth factor (HGF), an epithelial scattering factor, was expressed abundantly in cultivated AM epithelia. After blocking HGF function of AM, cultured SMG regained branching activity, reorganized cell adhesion and subcellular organization, and reproduced basement membranes. Therefore, AM-derived bioactive factor profoundly influences cell behaviors and structure formation of SMG. Together, this study showed that compositional topography of AM scaffold is important in affecting SMG morphogenesis. By understanding the effects of AM scaffold on SMG morphogenesis, it provides important information for rationally designing and fabricating AM scaffold for salivary gland regeneration.

Biomaterial mediated epithelial-mesenchymal interaction of salivary tissue under serum free condition.

Many organs develop from epithelial-mesenchymal interactions such that in order to regenerate these organs, it might be a preferable strategy to recapitulate this process. However, in the current culture system designed for tissue interaction, the supplement of serum is required. The aim of this study is to explore the possibility of reproducing epithelial-mesenchymal interaction and ensuing morphogenesis in a serum-free condition. In accordance with the previous studies, by using a standard model of murine fetal submandibular gland (SMG), the tissue interaction and the morphogenesis were largely dependent on serum. Nonetheless, when tissue recombinants were cultivated on polyvinylidene fluoride (PVDF), but not on other biomaterials, the serum-deprived effect could be rescued. On PVDF, SMG tissue recombinant was able to increase epithelial size, de novo synthesize basement membrane, and develop new branches without serum. Although the gene expression levels of selected morphogens were not significantly altered, the precise localization of morphogenetic-decisive extracellular matrix such as type III collagen and the superior adsorbing capacity of essential diffusible factors like fibroblast growth factor 7 (FGF7) might account for PVDF effect. Accordingly, the result demonstrates that it is possible to establish a serum-free system that is competent in facilitating epithelial-mesenchymal interaction of salivary tissue. With PVDF, the crosstalk between SMG epithelia and mesenchyme could be sustained without serum.

Characteristics of disc hemorrhage in primary angle-closure glaucoma.

PURPOSE: To analyze the characteristics of disc hemorrhage in primary angle-closure glaucoma (PACG). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Patients seen in glaucoma clinics with PACG and a history of disc hemorrhage. METHODS: Goldmann tonometry, gonioscopy, ophthalmoscopy, and automated perimetry. MAIN OUTCOME MEASURES: Location, number of episodes, and duration of disc hemorrhage; comparison of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in eyes with and fellow eyes without hemorrhage; and changes of CDR and visual fields (VFs) on follow-up. RESULTS: The mean duration of follow-up was 109.2+/-63 months (range, 7-261). Of 770 patients with PACG, 44 (5.7%) had disc hemorrhage at some point in their history, of whom 30 (68%) had unilateral and 14 (32%) had bilateral hemorrhages, either alternately or simultaneously in both eyes. There were a total of 111 hemorrhages in 58 eyes, including 23 eyes (40%) with recurrent hemorrhages. Of the 111 total hemorrhages, 85 (77%) occurred in the inferotemporal and 19 (17%) in the superotemporal sector of the disc. Among 23 eyes with recurrent disc hemorrhages, 11 (48%) had recurrence in the same sector of the disc. The average duration of hemorrhages was 12.8+/-8.1 weeks. The IOP and CDR did not differ significantly between eyes with and fellow eyes without hemorrhage. For patients with unilateral disc hemorrhage, progressive changes in the CDR were found in both the eyes with and fellow eyes without disc hemorrhage, but VF defects worsened only in eyes with disc hemorrhage. CONCLUSIONS: The incidence of disc hemorrhage in patients with PACG was 5.7% over 9 years of follow-up. Despite its relative infrequency, disc hemorrhage in PACG was associated with progression of glaucomatous optic neuropathy and VF defects.