Evaluation of trabecular meshwork-specific promoters in vitro and in vivo using scAAV2 vectors expressing C3 transferase.

AIM: To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies. METHODS: An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at different multiplicities of infections. Changes in cell morphology were observed by phase contrast microscopy. Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining, real-time quantitative polymerase chain reaction and Western blot. Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively. In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope. Intraocular pressure (IOP) was monitored using a rebound tonometer. Ocular responses were evaluated by slit-lamp microscopy. Ocular histopathology analysis was examined by hematoxylin and eosin staining. RESULTS: In TM cell culture studies, the vector-mediated C3 expression induced morphologic changes, disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rho-associated protein kinase signaling pathway. At the same dose, these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3, but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3. At low-injected dose, the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGP-C3-injected and scAAV2-eMGP-C3-injected eyes. At high-injected dose, significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes. Similar to scAAV2-CMV-C3, scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium. In anterior segment tissues of scAAV2-eMGP-C3-injected eyes, no obvious morphological changes were found except for the TM. Inflammation was absent. CONCLUSION: In scAAV2-transduced TM cells, the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus, but obviously higher than that of MGP. In the anterior chamber of rat eye, the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter, but not by Ch3L1 promoter. These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees.

AIM: To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract. METHODS: Two Chinese pedigrees with congenital cataract were investigated. Routine ophthalmic examinations were performed on all patients and non-affected family members. Peripheral blood samples were collected, and the genomic DNAs were extracted. The coding regions of proband's DNAs were analyzed with cataract gene panel. The identified mutation was amplified by polymerase chain reaction, and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease. RESULTS: Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees. For each family, more than half of the family members were affected. All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification. An exact the same defect in the same gene, a heterozygous mutation of c.70C>A (p. P24T) in exon 2 of γD-crystallin gene, was detected in both probands from each family. Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families. CONCLUSION: A c.70C>A (p. P24T) variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees. It is known that mutated CRYGD caused most of the congenital coralliform cataracts, suggesting that the CRYGD gene is associated with coralliform congenital cataract.

Comparing Computer-Assisted and Teacher-Implemented Visual Matching Instruction for Children with ASD and/or Other DD.

This paper compared the effectiveness and efficiency of using computer-assisted instruction (CAI) and teacher-implemented instruction (TII) to teach visual matching skills to students with autism spectrum disorder and/or other developmental disabilities. Four school-aged students participated in this study with an alternating treatment design. The CAI incorporated discrete trial instruction with the gesture-tracking application, while the TII involved traditional one-to-one instruction using flashcards. The results indicated that all students acquired the target matching skills with generalization to similar untaught skills and maintained acquired skills at a high level for up to 5 weeks under both CAI and TII. Both CAI and TII were effective. However, CAI was more efficient than TII in regards to the prompts provided and the duration of instructional sessions. CAI also resulted in more student engagement in independent learning.

Free 25-Vitamin D Is Correlated with Cardiovascular Events in Prevalent Hemodialysis Patients but Not with Markers of Renal Mineral Bone Disease.

Free vitamin D is the biologically active form of vitamin D. Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. The goal of our current study was to investigate the relation between blood concentrations of free 25-hydroxyvitamin D with cardiovascular events in end-stage chronic kidney disease patients on hemodialysis, because this is unknown so far. We measured free vitamin D levels in 117 stable consecutive prevalent patients in September as a surrogate of vitamin D exposure during the past 6 months, and recorded the number of cardiovascular events during the previous 6 months defined as hospitalization due to heart failure, episodes of acute coronary syndrome, and stroke. Fourteen events occurred during the observation period. In patients without any cardiovascular events the free vitamin D levels were significantly higher as compared to those with cardiovascular events (patients without events: 5.68 [4.37-9.27] pg/mL; patients with events: 4.74 [3.46-5.37] pg/mL, p = 0.015). This finding remained stable after multiple regression analysis considering confounding factors such as age, time on dialysis, preexisting diabetes, hypertension, and coronary heart disease. In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis.

Clinical observation of monocular rectus surgery for adult sensory exotropia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To evaluate the effect of monocular rectus surgery for adult sensory exotropia. <p>METHODS: Totally 76 cases of adult sensory exotropia of degree -15^△ to -160^△(-68.36^△±30.77^△)examined through Krimsky method were included into this study. A total of 16 cases, 37 cases and 23 cases with different degrees of strabismus were treated separately with routine amount monocular lateral rectus recession, routine amount monocular medial rectus resection plus lateral rectus recession, and exceed constant amount monocular medial rectus resection plus lateral rectus recession. Follow-up was performed at 1d, 1wk, 1, 3 and 6mo after operation. The eye position, monocular movement, intraocular pressure(IOP), slit lamp, and fundus of these patients were examined. <p>RESULTS:After surgery, 67 cases(88%)were positive and 9 cases(12%)were undercorrection. The postoperative intraocular pressure of operative eye at 1wk was equal to preoperative(<i>P</i>=0.090), and IOP decreased to a valley value at 1mo(<i>P</i><0.01), there was no significant difference in intraocular pressure between 3mo and 1mo(<i>P</i>=0.092), and no significant difference in intraocular pressure between 6mo and 3mo(<i>P</i>=0.123). And 2 cases(3%)had inflammatory reaction induced by anterior segment ischemia at 1d and 1wk postoperative visits, and they recovered at 1mo follow-up visit; 4 cases(5%)experienced an external dysfunction at the 1, 3 and 6mo follow-up. <p>CONCLUSION:Monocular rectus surgery has a good therapeutic effect on adult patients with sensory exotropia; the decrease in intraocular pressure secondary to the detached rectus is worth the attention of the surgeon; the incidence of complications after detaching monocular of two rectus muscles is comparable low. Exceed constant amount rectus strabismus surgery for sensory exotropia may result in limited function of postoperative ocular hyperextension.

[Treatment of Colles fracture with manipulative closed reduction and U-shaped gypsum functional fixation].

OBJECTIVE: To investigate the effect of U-shaped gypsum functional fixation after closed manipulative reduction for treatment of Colles' fractures. METHODS: From January 2011 to April 2014,47 cases of Colles fracture were treated by closed reduction and U-shaped gypsum functional fixation including 12 males and 35 females with an average age of 54.8 years old ranging from 8 to 72 years old. The time from injury to treatment was 40 min to 3 d. The patients were closed fractures without neurovascular injury. After manual reduction and U-shaped gypsum functional fixation, the thumb of injury hand were traction by contralateral hand, and other fingers of injury hand were taken flexion to exercise grip function. According to the situation of fracture healing, plaster was removed at 4 to 8 weeks' fixation, the wrist joint functional exercise was strengthened after plaster removed. RESULTS: All patients were followed up from 6 to 12 months with an average of 6.4 months, the fracture healing time was 4 to 8 weeks. According to the Cooney wrist function scoring: the result was excellent in 44 cases, good in 2 cases, 1 case. CONCLUSION: U-shape gypsum functional fixation for treatment of Colles fracture limits the activity of thumb and extensor tendon, can reduce shortening of radial by traction of the injury thumb with the contralateral hand; it is good for blood circulation of hand and wrist, and swelling.

Apex radicis dentis excision operation guided by template made by CAD/CAM.

OBJECTIVE: The aim of the study is to explore the clinical efficacy of apex radicis dentis excision guided by a template made by Computer Aided Design/Computer Aided Manufacture (CAD/CAM). METHODS: Base on the CBCT image of oral cavity, a three-dimensional model of patient's oral cavity was built. Then the access way and excisional area were defined based on the model. Finally, the operative guide template was designed and made to help define the direction, depth, and area of the surgery. RESULTS: One year after the operation with guide template, the two cases of apex radicis dentis with difficulty in cure were proven to have normal masticatory function and their pathological changes of apex radicis dentis disappeared as well. CONCLUSION: Utilization of CAD/CAM technology could well design the operative guide template for the resection of apex radicis dentis. Usingthis guide template could make the excision of apex radicis dentis more quickly and safer.

Neuroprotective effects of C3 exoenzyme in excitotoxic retinopathy.

The purpose of this study is to evaluate the neuroprotective effects of C3 exoenzyme (C3) on N-methyl-d-aspartate (NMDA)-induced retinopathy in rats. C3 was expressed in Escherichia. coli and purified by affinity chromatography. Immunofluorescence was performed in NIH 3T3 cells treated with C3 to verify the cellular uptake of the protein. NMDA was injected intravitreally into rat eyes with or without C3. At various time points after injection, eyes were enucleated. Hematoxylin/eosin staining was performed on retina cross-sections for morphological analysis. Survival and apoptosis of cells in the ganglion cell layer (GCL) were assessed by cresyl violet staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) on retina flat-mounts. RhoA levels in retina cells were evaluated by Western blot to detect C3 uptake in vivo. The cellular uptake of C3 was verified by immunofluorescence. Damage including a decrease in inner plexiform layer (IPL) thickness and reduction of cell density in the GCL, corresponding to apoptosis of neurons, was induced by intravitreal injection of NMDA. Protection against this damage was observed following co-injection of C3 and NMDA. RhoA ADP-ribosylation induced by C3 was confirmed by Western blot. Our results suggest that C3 exerts neuroprotective effects against excitotoxic damage induced by NMDA.

Single nucleotide polymorphism of MYOC affected the severity of primary open angle glaucoma.

AIM: To detect the mutations in two candidate genes, myocilin (MYOC) and cytochrome P450 1B1 (CYP1B1), in a Chinese family with primary open angle glaucoma (POAG). METHODS: The family was composed of three members, the parents and a daughter. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 genes were screened for sequence alterations by polymerase chain reaction (PCR) and direct DNA sequencing. RESULTS: The mother was the proband, she was diagnosed as POAG in both eyes. Her daughter was diagnosed as juvenile-onset POAG. The father was asymptomatic. One MYOC heterozygous mutation c.1150 G>A (D384N) in exon 3 was identified in the mother, another MYOC heterozygous variation c.1058 C>T (T353I) in exon 3 was identified in the father, and the daughter inherited both of the variations. Meanwhile, three single nucleotide polymorphisms (SNPs) in CYP1B1 gene were found in the family. CONCLUSION: The D384N mutation of MYOC has been reported as one of disease-causing mutations in POAG, whereas T353I variation of MYOC was thought as a high risk factor for POAG. The two variations of MYOC were first reported in one juvenile-onset POAG patient who presented with more severe clinical manifestations, suggesting that T353I polymorphism of MYOC may be associated with the severity of POAG.

A novel MYOC heterozygous mutation identified in a Chinese Uygur pedigree with primary open-angle glaucoma.

PURPOSE: To characterize the clinical features of a Chinese Uygur pedigree with primary open-angle glaucoma (POAG) and to identify mutations in two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1). METHODS: Twenty one members from a Chinese Uygur family of four generations were included in the study. All participants underwent complete ophthalmologic examinations. Five were diagnosed as POAG, four as glaucoma suspects, and the rest were asymptomatic. Molecular genetic analysis was performed on all subjects included in the study. All exons of CYP1B1 and MYOC were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. The variations detected were evaluated in available family members as well as 102 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis. RESULTS: Elevated intraocular pressure and late-stage glaucomatous cupping of the optic disc were found in five patients of this family. A novel heterozygous missense mutation c.1151 A>G in exon 3 of MYOC was found in all five patients diagnosed as POAG and four glaucoma suspects, but not in the rest of the family members and 102 normal controls. This mutation caused an amino acid substitution of aspartic acid to glycine at position 384 (p. D384G) of the MYOC protein. This substitution may cause structural and functional changes of the protein based on bioinformatics analysis. No mutations were found in CYP1B1. CONCLUSIONS: Our study suggests that the novel mutation D384G of MYOC is likely responsible for the pathogenesis of POAG in this pedigree.

A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism.

BACKGROUND: The purpose of this study was to elucidate the molecular basis of ocular albinism type I in a Chinese pedigree. METHODOLOGY/PRINCIPAL FINDINGS: Complete ophthalmologic examinations were performed on 4 patients, 7 carriers and 17 unaffected individuals in this five-generation family. All coding exons of four-point-one (4.1), ezrin, radixin, moesin (FERM) domain-containing 7 (FRMD7) and G protein-coupled receptor 143 (GPR143) genes were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Ocular albinism and nystagmus were found in all patients of this family. Macular hypoplasia was present in the patients including the proband. A novel nonsense hemizygous mutation c.807T>A in the GPR143 gene was identified in four patients and the heterozygous mutation was found in seven asymptomatic individuals. This mutation is a substitution of tyrosine for adenine which leads to a premature stop codon at position 269 (p.Y269X) of GPR143. CONCLUSIONS/SIGNIFICANCE: This is the first report that p.Y269X mutation of GPR143 gene is responsible for the pathogenesis of familial ocular albinism. These results expand the mutation spectrum of GPR143, and demonstrate the clinical characteristics of ocular albinism type I in Chinese population.

Experimental Tibetan monkey domestication and its application for intraocular pressure measurement.

AIM: To train Tibetan monkey (Macaca thibetana) for intraocular pressure (IOP) measurement in conscious state and obtain normal IOP in conscious Tibetan Macaque. METHODS: The training was based on award-conditioned behavior. Food stimulation and human-animal interaction were used in this training. RESULTS: Trained Tibetan monkeys calmly accepted IOP measurement by the TonoVet® rebound tonometer without sedation or anesthesia and their IOP values were similar to other primates. CONCLUSION: Human-cultivated Thibetan monkeys are tamable, and can be used for biomedical research such as ophthalmic research without anesthesia.

Is low dose of estrogen beneficial for prevention of glaucoma?

Glaucoma, as characterized by accelerated retinal ganglion cell (RGC) death and cupping of optic nerve head (ONH), is one of the leading causes of blindness worldwide. Elevated intraocular pressure (IOP) is generally considered as a major risk factor in the pathogenesis of glaucoma. Previous studies showed that glaucoma caused decrease in collagen and elastin density in several ocular tissues, such as lamina cribrosa, peripapillary sclera and cornea, and resulted in reduced elasticity and compliance of these tissues. It is known that estrogen has protective effects against glaucoma, yet the underlying mechanism still remains obscure. Prior researches have provided evidences showing that the estrogen receptors (ERs) express in a variety of the ocular tissues. Estrogen activates the synthesis of collagen fiber and improves the compliance of these tissues. This leads to a reasonable postulation that increased estrogen may result in a higher content of the collagen fibers and enhanced flexibility of the whole eye, which would therefore decrease IOP. Particularly, the increase in the amounts of collagen fibers at lamina cribrosa improves its compliance, which in turn relieves its compression on RGC axons. Therefore, even at the same IOP level, the softening of cribriform foramina yields a more flexible environment for the RGCs to survive. We therefore hypothesize that estrogen at proper dosage can be considered as a potential therapy for glaucoma since it is able to prevent the eye from glaucomatous damage and lower IOP, especially for those menopausal women with glaucoma.

Exome sequencing identifies compound heterozygous mutations in CYP4V2 in a pedigree with retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

Molecular genetics of familial nystagmus complicated with cataract and iris anomalies.

PURPOSE: Familial nystagmus complicated with cataract and iris anomalies are genetically heterogeneous, and the pathophysiological mechanisms remain unclear. It is anticipated that mutations in the paired box 6 (PAX6) gene play a major role in pathogenesis of malformations in anterior segment of the eye. In this study, we analyzed PAX6 in a Chinese pedigree of nystagmus, cataract and iris anomalies. This study will provide insights into the genetic basis of this disease. METHODS: Complete ophthalmologic examinations were performed on four patients (excluding one dead patient) and four unaffected individuals in this four-generation family. All coding exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database. The variations detected were evaluated in available family members as well as 110 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis. RESULTS: Nystagmus, cataract or iris anomalies were found in all patients of this family, but the severity was different among these patients. A novel missense mutation in PAX6 was identified in all affected individuals but not in asymptomatic members and 110 normal controls. This mutation causes an amino acid substitution of proline to glutamine at position 118 (p.P118Q) of the paired domain of the PAX6 protein. Such a change may cause structural and functional changes of the protein based on bioinformatics analysis. CONCLUSIONS: This study added a novel mutation to the existing spectrum of PAX6 mutations, suggesting that a mutation in PAX6 correlated with anterior segment disorders observed in this family.

Characterization of intraocular pressure responses of the Tibetan monkey (Macaca thibetana).

PURPOSE: To characterize the effects of circadian rhythm, feeding time, age, general anesthesia, and ocular hypotensive compounds on intraocular pressure (IOP) of the Tibetan monkey (Macaca thibetana). METHODS: Tibetan monkeys were trained for IOP measurement with the TonoVet® rebound tonometer without sedation or anesthesia. Their circadian IOP fluctuation was monitored every 3 h. Effects of changing the feeding time, general anesthesia, age (2-3 year-old versus 8-15 year-old animals), and various pharmacological agents, such as travoprost, timolol, naphazoline and spiradoline, on IOP were also evaluated. RESULTS: After behavioral training, conscious Tibetan monkeys were receptive to IOP measurement. The lowest and highest IOP values in a circadian cycle were recorded at 3:00 AM (19.8±0.4 mmHg, mean±SEM, n=12) and noon (29.3±0.9 mmHg), respectively. Changing the feeding time from 11:30 AM to 12:30 PM lowered the noon IOP to 25.1±1.2 mmHg. General anesthesia lowered IOP in these monkeys, while IOP of young and mature animals were similar. Three hours after topical ocular administration, travoprost reduced IOP by 5.2±0.6 mmHg (n=6, p<0.001), and timolol reduced IOP by 2.8±0.7 mmHg (p<0.05). Naphazoline and spiradoline lowered IOP by 4.8 mmHg and 2.5 mmHg (both p<0.001), respectively, 2 h after drug administration. CONCLUSIONS: The circadian IOP fluctuation in conscious Tibetan monkeys and their responses to travoprost, timolol, and other experimental conditions are similar to other primates. These monkeys appear to be a suitable model for glaucoma research.

Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of primary open-angle glaucoma.

PURPOSE: To analyze two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1), in a Chinese pedigree of primary open-angle glaucoma. METHODS: In a three-generation family containing 14 members, four of them were patients with primary open-angle glaucoma, one was a glaucoma suspect, and the rest were asymptomatic. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: Elevated intraocular pressure and impaired visual field were found in all patients. One MYOC heterozygous mutation G367R, in exon 3 was identified in four patients and the suspect, but not in the rest of the family members. Meanwhile, four single nucleotide polymorphisms in MYOC and CYP1B1 genes were found. CONCLUSIONS: Although the G367R mutation of MYOC, which causes primary open-angle glaucoma in the form of autosomal dominant inheritance, has been reported in some other ethnicities, it was found in Chinese pedigree for the first time.

Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bücklers corneal dystrophy.

AIM: To analyze mutations in transforming growth factor beta-induced (TGFBI) gene in a Chinese pedigree with Reis-Bücklers corneal dystrophy (RBCD, also known as GCD3). METHODS: In a five-generation Chinese family, eight members were identified with RBCD and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: A single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all the affected members of the pedigree, but not in the unaffected members. CONCLUSION: R124C which was a known mutation for lattice corneal dystrophy type I, segregated with the RBCD in this pedigree. This elucidated the correlation between genotype and phenotype in a Chinese family of RBCD.

Inhibition of latrunculin-A on dexamethasone-induced fibronectin production in cultured human trabecular meshwork cells.

AIM: To determine the effects of a low dose latrunculin (LAT)-A on dexamethasone (Dex)-induced upregulation of extracellular matrix proteins fibronectin (FN) in cultured human trabecular meshwork (HTM) cells. METHODS: HTM cells were cultured to confluent and incubated with 0.4µmol/L Dex and/or 0.05µmol/L LAT-A. FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy. RESULTS: Dex up-regulated FN production in HTM cells, failed to do so when co-incubated with LAT-A. LAT-A decreased production of FN in cultured HTM cells. CONCLUSION: This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma. It has an important prospect as an intraocular pressure- lowering drug.