Novel Genetic Findings in a Chinese Family with Axenfeld-Rieger Syndrome.

PURPOSE: To describe a Chinese family with Axenfeld-Rieger syndrome (ARS) and report our novel genetic findings. METHODS: Nine members of the same family underwent complete ophthalmologic examinations and genetic analysis. Genomic DNA was isolated from veinal blood and amplifed using PCR; the products of PCR were sequenced and compared with FOXC1 and PITX2 genes, from which the mutations were found. RESULTS: Through the ophthalmologic examinations, 8 subjects were diagnosed as ARS and 1 subject was normal. A homozygous mutation c.1139_1141dupGCG(p.Gly380_Ala381insGly) and a heterozygous mutation c.1359_1361dupCGG(p.Gly456_Gln457insGly) in FOXC1 were identified in all subjects. The mutation (c.-10-30T>C) was identified in PITX2 in subjects III-1 and III-3. CONCLUSIONS: We found novel gene mutations in a Chinese family with ARS, which provides us with a better understanding of the gene mutation spectrum of ARS and the assistance for the genetic counseling and gene-specific therapy in the future.

Dexamethasone distribution characteristic following controllable continuous sub-tenon drug delivery in rabbit.

Drug delivery systems are required to be safe, minimally invasive and effectively delivery drug to the target tissues. But delivery drugs to the eye has not yet satisfied this need. Here, we focused on examining the distribution of dexamethasone (DEX) in ocular and plasmic samples following controllable continuous sub-Tenon drug delivery (CCSDD) of dexamethasone disodium phosphate (DEXP) in rabbit, and to compare that with two traditional routes: subconjunctival injection and intravenous injection. The DEX concentration was analyzed by Shimadzu LC-MS 2010 system. In CCSDD group, during observed 24 h, the mean DEX level in collected samples from highest to lowest following in order: sclera, cornea, retina/choroid, iris, plasma, aqueous humor, lens and vitreous body. In ocular solid tissue, the DEX level in posterior segment is higher than in anatomic corresponding anterior segment, but it is opposite in ocular fluid tissue. High levels of DEX were maintained at 12 h in the ocular tissue immediately after the administration. Even at 24 h, the mean DEX concentration was 31.72 ng/ml and 22.40 ng/ml in aqueous and vitreous, respectively. In CCSDD group, the ocular DEX exposure (AUC0-24) is much higher and plasma exposure is much less than IV group, and it is also similar in SC group except iris. The amount of DEX levels are markedly increased in ocular tissues but it yield lower plasma levels indicating reduction of systemic absorption by CCSDD. Thus, CCSDD is an effective method of delivering DEX into anterior and posterior segment of the eye.

Opacification of a Hydrophilic Acrylic Intraocular Lens.

Opacification of a hydrophilic acrylic intraocular (IOL) lens is a rare phenomenon. We herein report a case of a 57-year man complaining of decreased vision at left eye for the last 4 months. He had undergone phacoemulsification with IOL implantation 2 years back. IOL opacification was observed through slit-lamp. IOL exchange was carried out. The exchanged IOL and a new lens of the same model were sent to laboratory for pathologic analysis. Confocal microscopy showed uniformly distributed granules from the surface to 80 µm internal surface. Scanning electron microscopy (SEM) showed the details of granules. X-ray photoelectron spectroscopy (XPS) confirmed the presence of calcium and silicon in the deposits. Aqueous humor biochemical analysis revealed a normal result. We discuss the possible causes of opacification of IOL in this report.

Experience-dependent expression of Nogo-A and Nogo receptor in the developing rat visual cortex.

Nogo-A and Nogo receptor (NgR) expression in the visual cortex following a critical developmental period (postnatal days 20-60) has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points: postnatal day 0 (P0), before critical period (P14), during critical period (P28), and after critical period (P60). Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers II-III and IV in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.

Reactivation of visual cortical plasticity by NEP1-40 from early monocular deprivation in adult rats.

Amblyopia is difficult to cure in adult due to the declination of visual cortical plasticity with age. However, the mechanisms limiting adult cortical plasticity are still unclear. Inhibition factors associated with myelin are suggested to be crucial for the ocular dominance plasticity in the visual cortex. We hypothesize that blocking Nogo-NgR system with NEP1-40 in adult visual cortex will reactivate the structural and functional plasticity. To back up this hypothesis, we subjected postnatal day 21 (P21) rats to monocular deprivation (MD) model until P45. Then the deprived eyes of MD model rats were reopened and followed by NEP1-40 or PBS administration for 7days. Dendritic spine densities, ultrastructral modifications of synaptic junctions and objective visual function were examined at P52 to determine the therapeutic effects of NEP1-40. Our findings suggest a new curative role for NEP1-40 in structural and functional recovery from the deficits of adult MD rats, and offer a potential therapeutic tool for curing amblyopia and other cortically based visual disorders.