Rotational stability of a new multicomponent intraocular lens.

PURPOSE: To evaluate the rotational stability of the Precisight multicomponent intraocular lens (MCIOL) following primary implantation and after enhancement procedures. PATIENTS AND METHODS: Prospective, single-center study of eyes that underwent routine cataract surgery with implantation of a non-toric MCIOL, (Precisight, InfiniteVision, Optics, Strasbourg, France). The axis of the MCIOL was measured with a line bisecting the two dialing holes in the front lens. Intraoperative orientation was determined using a digital surgical guidance system while the postoperative orientation was determined using slit-lamp imaging. Two populations were analyzed: eyes that only underwent cataract surgery (PRIM) and eyes that also underwent enhancement (ENH), consisting of surgical front optic exchange. Both populations had 3 observation visits: first implantation (P-Op); 3 months (3mo) and 6 months (6mo) after primary surgery. The ENH group had an additional fourth visit that corresponded to the enhancement surgery (E-Op). The main outcome measure was mean absolute change in MCIOL orientation (degrees). The effects of axial length (AL) and anterior chamber depth (ACD) on IOL rotational stability were examined. RESULTS: Thirty-three eyes received MCIOL of which 29 had usable orientation images. Of these, 12 were in the PRIM group and 17 underwent ENH. Regarding the mean absolute rotation, among PRIM eyes, P-Op to 3mo was 3.03±2.45 degrees; P-Op to 6mo, 2.28±1.54 degrees; and 3-6mo, 2.37±1.56 degrees. Among the ENH eyes, P-Op to 3mo was 3.09±1.68; E-Op to 6mo, 2.71±3.30 and P-Op to 6mo, 3.62±3.42. There were no significant differences in the IOL rotation. There were no statistical differences in rotational stability between the ENH and PRIM groups. There was no correlation between IOL rotation and AL or ACD. CONCLUSION: Precisight appears to be rotationally stable. The enhancement procedure does not affect rotational stability.

Enhancement-procedure outcomes in patients implanted with the Precisight multicomponent intraocular lens.

PURPOSE: Eyes that have undergone phacoemulsification with implantation of a multicomponent intraocular lens (MCIOL) may further undergo an enhancement procedure for correction of residual refractive errors. The enhancement procedure is accomplished by exchanging the front lens used in the primary surgery with another lens containing the correct dioptric power. We evaluated the efficacy and safety of enhancement procedures among eyes that received an MCIOL. METHODS: A total of 25 eyes that had undergone phacoemulsification with implantation of an MCIOL were found to have a residual error of refraction (spherical equivalent ≥0.75 D) 3 months after primary cataract surgery, and underwent further enhancement surgery. The main study outcomes were uncorrected and corrected distance visual acuity, subjective refraction, anterior-chamber depth, pachymetry, and endothelial cell count. RESULTS: There was a statistically significant improvement in uncorrected distance visual acuity of approximately two lines after enhancement surgery (0.20±0.20-0.02±0.08 logMAR, P<0.001) and a significant decrease in residual spherical equivalent from 1.3±1.1 D to 0±0.38 D (P<0.001). There were no statistically significant changes in pre- and postenhancement corrected distance visual acuity, anterior-chamber depth, pachymetry, or keratometry. There was a statistically significant decrease (2.6%) in endothelial cell count (P<0.01), which could have been endothelial equilibration from the primary procedure. All enhancement surgeries were uneventful, and no major complications were observed. CONCLUSION: The MCIOL-enhancement procedure demonstrates statistical and clinical improvement in uncorrected distance visual acuity and correction of postoperative refractive errors. The Precisight IOL may be a useful choice for patients with high risk of having significant residual refractive errors after primary cataract surgery.

Vulnerability to opiate intake in maternally deprived rats: implication of MeCP2 and of histone acetylation.

We previously showed that maternal deprivation predisposes male rats to anxiety, accompanied with an increase in their opiate consumption. In the present report, we searched for brain epigenetic mechanisms that possibly underlie this increase. For that, we examined the expression of the methyl-CpG-binding protein MeCP2 and of the histone deacetylases HDAC2 and HDAC3, as well as the acetylation status of histone H3 and H4 in mesolimbic structures of adult maternally deprived rats, using immunohistochemistry and Western blot analysis. A long-lasting increase in MeCP2 expression was found throughout the striatum of deprived rats. Enhanced HDAC2 expression and increased nuclear HDAC activity in the nucleus accumbens of deprived rats were associated with lower acetylation levels of histone H3 and H4. Treatment for 3 weeks with the HDAC inhibitor sodium valproate abolished HDAC activation together with the decrease in the acetylation levels of histone H4, and was accompanied with normalized oral morphine consumption. The data indicate that epigenetic mechanisms induced by early adverse environment memorize life experience to trigger greater opiate vulnerability during adult life. They suggest that sodium valproate may lessen vulnerability to opiate intake, particularly in subgroups of individuals subjected to adverse postnatal environments.

Differential regulation of MeCP2 and PP1 in passive or voluntary administration of cocaine or food.

Cocaine exposure induces changes in the expression of numerous genes, in part through epigenetic modifications. We have initially shown that cocaine increases the expression of the chromatin remodeling protein methyl-CpG binding protein 2 (MeCP2) and characterized the protein phosphatase-1Cß (PP1Cß) gene, as repressed by passive i.p. cocaine injections through a Mecp2-mediated mechanism involving de novo DNA methylation. Both proteins being involved in learning and memory processes, we investigated whether voluntary cocaine administration would similarly affect their expression using an operant self-administration paradigm. Passive and voluntary i.v. cocaine intake was found to induce Mecp2 and to repress PP1Cß in the prefrontal cortex and the caudate putamen. This observation is consistent with the role of Mecp2 acting as a transcriptional repressor of PP1Cß and shows that passive intake was sufficient to alter their expression. Surprisingly, striking differences were observed under the same conditions in food-restricted rats tested for food pellet delivery. In the prefrontal cortex and throughout the striatum, both proteins were induced by food operant conditioning, but remained unaffected by passive food delivery. Although cocaine and food activate a common reward circuit, changes observed in the expression of other genes such as reelin and GAD67 provide new insights into molecular mechanisms differentiating neuroadaptations triggered by each reinforcer. The identification of hitherto unknown genes differentially regulated by drugs of abuse and a natural reinforcer should improve our understanding of how two rewarding stimuli differ in their ability to drive behavior.

Differential patterns of expression of neuropeptide Y throughout abstinence in outbred Swiss mice classified as susceptible or resistant to ethanol-induced locomotor sensitization.

Several studies have focused on the negative emotional state associated with drug abstinence. The peptide NPY plays an important role given its involvement in drug addiction, anxiety, and mood disorders. Interestingly, it is well established that outbred Swiss mice exhibit a prominent behavioral variability to ethanol-induced locomotor sensitization. Here, we investigated whether mice that were either susceptible or resistant to ethanol sensitization differed in their NPY expression during abstinence. The mice were treated daily with ethanol (2 g/kg, i.p.) or saline for 21 days. According to the locomotor activity after the last injection, the ethanol group was classified as sensitized (EtOH_High) or non-sensitized (EtOH_Low). To evaluate NPY expression, some of the mice were sacrificed at 18 h or 5 days of abstinence, and others were challenged at the 5th day of abstinence with ethanol (1.4 g/kg) and sacrificed after 1.5 h. At 5 days of abstinence, NPY expression increased in the orbital cortex, dorsomedial striatum, and dentate gyrus in the EtOH_High mice. These changes were counteracted by the ethanol challenge. In the EtOH_Low mice, NPY expression increased in the dentate gyrus only after 18 h of abstinence. Lastly, a decreased level of NPY was found in the prelimbic cortex of the EtOH_Low mice at 5 days of abstinence, and this was reversed by ethanol challenge. Therefore, behavioral variability in ethanol sensitization confers differential neurochemical features during the subsequent abstinence, including distinct patterns of NPY expression.

Effects of ethanol on hippocampal neurogenesis depend on the conditioned appetitive response.

Neurogenesis in the subgranular layer of the dentate gyrus (DG) has been suggested to underlie some forms of associative learning. The present study was undertaken to determine whether there was also a role of neurogenesis in the ethanol (EtOH)-induced conditioned place preference (CPP). Outbreed Swiss mice were conditioned with EtOH (2.0 g/kg) in one compartment of a non-biased place preference chamber and saline in the other compartment. This procedure produced three groups of mice: some developed a conditioned preference (EtOH_Cpp), others developed a conditioned avoidance (EtOH_Cpa) and still others demonstrated indifference to the context previously paired with ethanol (EtOH_Ind). BrdU (40 mg/kg, i.p.) was administered 4 hours after each session comprising the conditioning phase. When measured 24 hours following the CPP test, there was no effect of EtOH on doublecortin (DCX) expression or Fluoro Jade B staining. However, there were decreases in the number of BrdU+ and Ki-67+ cells in the EtOH_Cpa and EtOH_Ind groups, but not in the EtOH_Cpp group. Most of BrdU+ cells were co-labeled with DCX. Similarly, in another experiment, in that the perfusion was done 28 days after CPP test, most BrdU+ cells were co-localized with NeuN. These results suggest that conditioned appetitive response is able to maintain normal levels of neurogenesis in DG and might counteract ethanol-produced decreased cell proliferation/survival rate.