MYOC encodes a secretary glycoprotein of 504 amino acids named myocilin. MYOC is the first gene to be linked to juvenile open-angle glaucoma (JOAG) and some forms of adult-onset primary open-angle glaucoma (POAG). The gene was identified as an up-regulated molecule in cultured trabecular meshwork (TM) cells after treatment with dexamethasone and was originally referred to as trabecular meshwork-inducible glucocorticoid response (TIGR). Elevated intraocular pressure (IOP), due to decreased aqueous outflow, is the strongest known risk factor for POAG. Increasing evidence showed that the modulation of the wild-type (wt) myocilin protein expression is not causative of glaucoma while some misfolded and self-assembly aggregates of mutated myocilin may be associated with POAG in related or unrelated populations. The etiology of the disease remains unclear. Consequently, a better understanding of the molecular mechanisms underlyingPOAG is required to obtain early diagnosis, avoid potential disease progression, and develop new therapeutic strategies. In the present study, we review and discuss the most relevant studies regarding structural characterizations, expressions, molecular interactions, putative functions of MYOC gene and/or its corresponding protein in POAG etiology.

Objective: To investigate the association between antenatal maternal corticosteroid administration and blood levels of reactive oxygen intermediates (ROI), reduced glutathione (GR) and interleukin-6 (IL-6) in preterm, very low birth weight infants. Methods:This was a cohort study in which cord blood samples were used for the following tests: baseline and stimulated granulocyte ROI were measured by flow cytometry; GR was assayed by spectrophotometry; and IL-6 by enzyme-linked immunosorbent assay. Two different comparative analyses of antenatal corticosteroid (betamethasone) were conducted: the first compared administration against no administration and the second compared mothers who received the complete cycle with those given only a partial antenatal corticosteroid cycle. Maternal and neonatal variables were analyzed in order to compare groups. Categorical variables were compared using the chi-square or Fischer tests, and blood marker test results were compared using the Mann-Whitney test. Results:The different corticoid therapy groups were similar in terms of all of the maternal and neonatal variables with the exception of vaginal delivery, which was significantly associated with not receiving antenatal corticosteroid. The results for ROI, GR and IL-6 did not differ when the comparison was based on simple presence or absence of administration of the steroid. However, when the complete cycle was compared against incomplete administration, median ROI and IL-6 were lower among those given the complete cycle. Conclusion:Administration of the complete cycle of betamethasone to the mother had a suppressive effect on baseline ROI and IL-6 production in very low birth weight preterm newborn infants.J Pediatr (Rio J). 2012;88(1):61-6: Newborn, oxidative stress, reactive oxygen species, interleukin-6, glutathione. ResumoObjetivo: Avaliar a associação entre o uso materno antenatal de corticosteroide e os níveis sanguíneos de intermediários reativos de oxigênio (ROI), glutationa reduzida (GR) e interleucina-6 (IL-6) em recém-nascidos pré-termo de muito baixo peso ao nascer.Métodos: Estudo de coorte. A dosagem foi feita em sangue de cordão umbilical. A dosagem de ROI por granulócitos foi realizada por citometria de fluxo nos estados basal e estimulado; a GR, por espectrofotometria; e a IL-6, por enzyme-linked immunosorbent assay. Foram considerados dois grupos em relação ao uso de corticosteroide (betametasona) antenatal: uso ou não da medicação; e, se presente, se foi de modo completo ou parcial. Variáveis maternas e neonatais foram consideradas para efeito de comparação dos grupos. As variáveis categóricas foram comparadas usando os testes do qui-quadrado ou de Fischer, e as comparações dos valores dos marcadores sanguíneos foram feitas usando-se o teste de Mann-Whitney.Resultados: Os grupos de corticoterapia foram comparáveis em relação às variáveis maternas e neonatais, exceto a ocorrência de parto vaginal, o qual foi associado significativamente à ausência de uso de corticosteroide antenatal. Os valores de ROI...

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ROI, GSH, and IL-6 levels were not associated with the occurrence of PIVH in very-low birth weight infants.

Mutations in the myocilin gene (MYOC) account for most cases of autosomal dominant juvenile-onset open-angle glaucoma (JOAG), an earlier and more severe form of POAG. We accessed seven members of a Brazilian JOAG family by clinical and molecular investigation. Four out of seven family members were diagnosed with JOAG. All of these patients presented high intraocular pressure and two of them were bilaterally blind. The disease onset varied from 20 to 30years old. There was a nine-year-old family member who had not yet manifested the disease, although he was also a carrier of the mutation. Ophthalmologic examination included: evaluation of the visual field and optic disc, intraocular pressure measurement, and gonioscopy. The three exons and intron/exon junctions of the MYOC gene were screened for mutations through direct sequencing of PCR-amplified DNA fragments. Mutation screening revealed an in-frame mutation in the third exon of the MYOC gene: an insertion of six nucleotides between the cDNA positions 1187 and 1188 (c.1187_1188insCCCAGA, p.D395_E396insDP). This mutation presented an autosomal dominant pattern of inheritance, segregating with the disease in four family members for three generations, and it was absent in 60 normal controls. We also performed a computational structure modeling of olfactomedin-like domain of myocilin protein and conducted in silico analysis to predict the structural changes in the myocilin protein due to the presence of the mutation. These findings may be important for future diagnosis of other presymptomatic family members, as well as for the increase of the panel of MYOC mutations and their effects on phenotype.