Mutation analysis of connexin 50 gene among Iranian families with autosomal dominant cataracts.

OBJECTIVES: Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin 50 gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC). MATERIALS AND METHODS: Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist's examination, and the pedigree analysis was performed. PCR amplifications were performed corresponding to coding region and intron-exon boundaries of GJA8, a candidate gene responsible for ADCC. PCR products were subjected to bidirectional sequencing, and the co-segregation of identified mutations was examined and finally, the impact of identified mutations on biological functions of GJA8 was predicted by in silico examination. RESULTS: Three different genetic alterations, including c.130G>A (p.V44M), c.301G>T (p.R101L) and c.134G>T (p.W45L) in GJA8 gene were detected among three probands. Two identified mutations, W45L and V44M have been already reported, while the R101L is a novel mutation and its co-segregation was examined. This mutation was exclusively detected in the ADCC and could not be found among the healthy control group. The result of bioinformatic studies of R101L mutation predicted that this amino acid substitution within GJA8 could be a disease-afflicting mutation due to its potential effect on the protein structure and biological function. CONCLUSION: Our results suggest that mutations of lens connexin genes such as GJA8 gene could be one of the major mechanisms of cataract development, at least in a significant proportion of Iranian patients with ADCC.

Mini-scleral Contact Lens for Management of Poor Visual Outcomes after Intrastromal Corneal Ring Segments Implantation in Keratoconus.

PURPOSE: To evaluate the feasibility and efficacy of mini-scleral design (MSD) contact lenses to treat keratoconus patients who were unsatisfied with the results of corneal inlay. METHODS: In this prospective interventional case series, 9 eyes of 6 keratoconus patients who were unsatisfied with the results of corneal inlay were fitted with MSD contact lenses. Demographic data, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and higher order aberrations (HOAs) were evaluated before contact lens fitting. Corrected visual acuity by placing the MSD contact lens with or without over-refraction, and HOAs were measured one hour after contact lens fitting. One month after contact lens wearing, corrected visual acuity by placing the MSD contact lens with over-refraction and possible contact lens related problems were assessed. Ocular comfort and contact lens handling problems were asked in follow-up visits. The data was analyzed using descriptive statistical tests. RESULTS: Nine eyes of 6 patients were successfully fitted with the mini-scleral lens. Fitting was ideal in 7 eyes and acceptable in 2 eyes. Mean corrected visual acuity by placing the MSD lens without over-refraction was 0.09 (range, 0.00-0.15) LogMAR which was significantly better than the mean BSCVA of 0.38 (range, 0.2-0.6) LogMAR (P = 0.007). The mean root mean square (RMS) of third-order coma and trefoil significantly decreased after MSD contact lens fitting (P = 0.012 and P = 0.015, respectively); however, changes in the fourth-order spherical aberration were not statistically significant (P = 0.336). CONCLUSION: Mini-scleral contact lenses may be helpful in the management of visually unsatisfied patients after corneal inlay.

Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX) Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal.

A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.

Evaluation of SD-208, a TGF-ß-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-ß-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment.

Identification of a De Novo 3bp Deletion in CRYBA1/A3 Gene in Autosomal Dominant Congenital Cataract.

Autosomal dominant congenital cataract (ADCC) is the most common form of inherited cataracts and accounts for one-third of congenital cataracts. Heterozygous null mutations in the crystallin genes are the major cause of the ADCC. This study aims to detect the mutational spectrum of four crystallin genes, CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD in an Iranian family. Genomic DNA was isolated from whole blood cells from theproband and other family members. The coding regions and flanking intronicsequences of crystalline genes were analyzed by Sanger sequencing in aproband with ADCC. The identified mutation was further evaluated in available family members. To predict the potential protein partners of CRYBA1/A3, we also used an in-silico analysis. A de novo heterozygous deletion (c.272-274delGAG, p.G91del) in exon 4 of CRYBA1/A3 gene, leading to a deletion of Glycine at codon 91 was found. This genetic variation did not change the reading frame of CRYBA1 protein. In conclusion, we identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling.

Work-related eye injury: the main cause of ocular trauma in Iran.

PURPOSE: Occupational eye injuries are among the major causes of ocular trauma and can cause severe visual impairment, with even minor injuries incurring considerable financial costs due to work absenteeism. This study was designed to evaluate the epidemiology of eye trauma and the role of occupational injuries at Farabi Eye Hospital, which is the largest eye hospital in Iran. METHODS: In this prospective, cross-sectional study, 822 eyes from 768 trauma patients presenting to Farabi Eye Hospital were enrolled in the study. The Birmingham Eye Trauma Terminology System and the United States Eye Injury Registry model were adopted as the basis for the study questionnaire. The questionnaires were completed through in-person interviews and comprehensive ocular examinations. RESULTS: The mean age of ocular trauma patients was 31.11 years, and 685 (89.2%) patients were male. Of all eye injuries, 73.7% were work-related. Only 2.2% of the patients were wearing safety goggles at the time of injury. History of previous eye trauma was positive in 44.3% of cases. An Ocular Trauma Score 3 or more was present in 4% of patients. CONCLUSIONS: Work-related eye trauma is the major cause of eye injury in Iran and most often occurs as a result of the lack of proper eye protection. Most work-related eye injury patients are young men.