Has recombination changed during the recent evolution of the guppy Y chromosome?

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms. We used molecular markers to directly estimate genetic maps in sires from 4 guppy populations. The maps are very similar, suggesting that their crossover patterns have not recently changed. Our maps are consistent with population genomic results showing that variants within the terminal 5 Mb of the 26.5 Mb sex chromosome, chromosome 12, are most clearly associated with the maleness factor, albeit incompletely. We also confirmed occasional crossovers proximal to the male-determining region, defining a second, rarely recombining, pseudo-autosomal region, PAR2. This fish species may therefore have no completely male-specific region (MSY) more extensive than the male-determining factor. The positions of the few crossover events suggest a location for the male-determining factor within a physically small repetitive region. A sex-reversed XX male had few crossovers in PAR2, suggesting that this region's low crossover rate depends on the phenotypic, not the genetic, sex. Thus, rare individuals whose phenotypic and genetic sexes differ, and/or occasional PAR2 crossovers in males can explain the failure to detect fully Y-linked variants.

A lncRNA-encoded mitochondrial micropeptide exacerbates microglia-mediated neuroinflammation in retinal ischemia/reperfusion injury.

As a common pathology of many ocular disorders such as diabetic retinopathy and glaucoma, retinal ischemia/reperfusion (IR) triggers inflammation and microglia activation that lead to irreversible retinal damage. The detailed molecular mechanism underlying retinal IR injury, however, remains poorly understood at present. Here we report the bioinformatic identification of a lncRNA 1810058I24Rik (181-Rik) that was shown to encode a mitochondrion-located micropeptide Stmp1. Its deficiency in mice protected retinal ganglion cells from retinal IR injury by attenuating the activation of microglia and the Nlrp3 inflammasome pathway. Moreover, its genetic knockout in mice or knockdown in primary microglia promoted mitochondrial fusion, impaired mitochondrial membrane potential, and reactive oxygen species (ROS) production, diminished aerobic glycolysis, and ameliorated inflammation. It appears that 181-Rik may trigger the Nlrp3 inflammasome activation by controlling mitochondrial functions through inhibiting expression of the metabolic sensor uncoupling protein 2 (Ucp2) and activating expression of the Ca2+ sensors S100a8/a9. Together, our findings shed new light on the molecular pathogenesis of retinal IR injury and may provide a fresh therapeutic target for IR-associated neurodegenerative diseases.

The mitochondrial micropeptide Stmp1 promotes retinal cell differentiation.

During mammalian retinal development, the differentiation of multipotent progenitors depends on the coordinated action of a variety of intrinsic factors including non-coding RNAs (ncRNAs). To date, many small open reading frames have been identified in ncRNAs to encode micropeptides that function in diverse biological processes; however, it remains unclear whether they have a role in retinal development. Here we report that the 47-amino acid (AA) mitochondrial micropeptide Stmp1 encoded by the lncRNA 1810058I24Rik is involved in retinal differentiation. As the major protein product of 1810058I24Rik, Stmp1 promotes the differentiation of bipolar, amacrine and Müller cells as 1810058I24Rik does when overexpressed in neonatal murine retinas. Moreover, we have identified the 15-AA N-terminus of Stmp1 as its mitochondrion-targeting sequence as well as 5 conserved AA residues that affect protein stability and/or retinal cell differentiation. Together, our data reveal several novel characteristics of Stmp1 and uncover a role for Stmp1 in retinal cell differentiation perhaps through regulating mitochondrial function.

Partial sex linkage and linkage disequilibrium on the guppy sex chromosome.

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding this fish's sex-determining locus, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger "evolutionary strata". Sequences of the guppy genome show that Y is very similar to the X chromosome. Knowing which parts of the Y are completely nonrecombining, and whether there is indeed a large completely nonrecombining region, are important for understanding its evolution. Here, we describe analyses of PoolSeq data in samples from within multiple natural populations from Trinidad, yielding new results that support previous evidence for occasional recombination between the guppy Y and X. We detected recent demographic changes, notably that downstream populations have higher synonymous site diversity than upstream ones and other expected signals of bottlenecks. We detected evidence of associations between sequence variants and the sex-determining locus, rather than divergence under a complete lack of recombination. Although recombination is infrequent, it is frequent enough that associations with SNPs can suggest the region in which the sex-determining locus must be located. Diversity is elevated across a physically large region of the sex chromosome, conforming to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.

Genome-enabled discovery of candidate virulence loci in Striga hermonthica, a devastating parasite of African cereal crops.

Parasites have evolved proteins, virulence factors (VFs), that facilitate plant colonisation, however VFs mediating parasitic plant-host interactions are poorly understood. Striga hermonthica is an obligate, root-parasitic plant of cereal hosts in sub-Saharan Africa, causing devastating yield losses. Understanding the molecular nature and allelic variation of VFs in S. hermonthica is essential for breeding resistance and delaying the evolution of parasite virulence. We assembled the S. hermonthica genome and identified secreted proteins using in silico prediction. Pooled sequencing of parasites growing on a susceptible and a strongly resistant rice host allowed us to scan for loci where selection imposed by the resistant host had elevated the frequency of alleles contributing to successful colonisation. Thirty-eight putatively secreted VFs had very different allele frequencies with functions including host cell wall modification, protease or protease inhibitor and kinase activities. These candidate loci had significantly higher Tajima's D than the genomic background, consistent with balancing selection. Our results reveal diverse strategies used by S. hermonthica to overcome different layers of host resistance. Understanding the maintenance of variation at virulence loci by balancing selection will be critical to managing the evolution of virulence as part of a sustainable control strategy.

An optimized procedure to record visual evoked potential in mice.

Visual evoked potential (VEP) is commonly used to evaluate visual acuity in both clinical and basic studies. Subdermal needle electrodes or skull pre-implanted screw electrodes are usually used to record VEP in rodents. However, the VEP amplitudes recorded by the former are small while the latter may damage the brain. In this study, we established a new invasive procedure for VEP recording, and made a series of comparisons of VEP parameters recorded from different electrode locations, different times of day (day and night) and bilateral eyes, to evaluate the influence of these factors on VEP in mice. Our data reveal that our invasive method is reliable and can record VEP with good waveforms and large amplitudes. The comparison data show that VEP is greatly influenced by active electrode locations and difference between day and night. In C57 or CD1 ONC (optic nerve crush) models and Brn3bAP/AP mice, which are featured by loss of retinal ganglion cells (RGCs), amplitudes of VEP N1 and P1 waves are drastically reduced. The newly established VEP procedure is very reliable and stable, and is particularly useful for detecting losses of RGC quantities, functions or connections to the brain. Our analyses of various recording conditions also provide useful references for future studies.

In vivo Regeneration of Ganglion Cells for Vision Restoration in Mammalian Retinas.

Glaucoma and other optic neuropathies affect millions of people worldwide, ultimately causing progressive and irreversible degeneration of retinal ganglion cells (RGCs) and blindness. Previous research into cell replacement therapy of these neurodegenerative diseases has been stalled due to the incapability for grafted RGCs to integrate into the retina and project properly along the long visual pathway. In vivo RGC regeneration would be a promising alternative approach but mammalian retinas lack regenerative capacity. It therefore has long been a great challenge to regenerate functional and properly projecting RGCs for vision restoration in mammals. Here we show that the transcription factors (TFs) Math5 and Brn3b together are able to reprogram mature mouse Müller glia (MG) into RGCs. The reprogrammed RGCs extend long axons that make appropriate intra-retinal and extra-retinal projections through the entire visual pathway to innervate both image-forming and non-image-forming brain targets. They exhibit typical neuronal electrophysiological properties and improve visual responses in RGC loss mouse models. Together, our data provide evidence that mammalian MG can be reprogrammed by defined TFs to achieve in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.

αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.

Increased Levels of DKK1 in Vitreous Fluid of Patients with Pathological Myopia and the Correlation between DKK1 Levels and Axial Length.

Purpose: Dickkopf 1 (DKK1) functions as a natural antagonist of the canonical Wnt/ß-catenin pathway. The purpose of this study was to examine the expression of DKK1 in vitreous samples of patients with pathological myopia, in order to search for possible correlations between DKK1 and axial length.Materials and Methods: The expression of DKK1 and other cytokines in vitreous samples of 44 non-myopic eyes, 42 eyes with low-to-moderate myopia, and 51 eyes with pathological myopia were examined using multiplex cytokine detection technology. Ophthalmologic characteristics, including axial length and subfoveal choroidal thickness, were clinically measured for further analysis.Results: The intravitreous levels of DKK1 (P < .0001) were markedly higher in the pathological myopia group than in the control group. There were no differences of DKK1 levels in different vitreoretinal conditions. Additionally, we found that the DKK1 levels were positively correlated with HGF (ß = 0.268, P = .032), and TIMP-3 (ß = 0.209, P = .047) levels, as well as with axial length (ß = 0.714, P < .0001) in the pathological myopia group.Conclusions: Elevated levels of DKK1 were found in the eyes with elongated axial length.

Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas.

In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis2-7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of ß-catenin stimulates MG proliferation in the absence of injury in mouse retinas8. Here we report that following gene transfer of ß-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.

Intravitreal injection of docosahexaenoic acid attenuated photoreceptor cell injury in a NaIO3-induced age-related macular degeneration rat model.

In most studies, the major supplement docosahexaenoic acid (DHA) is administered orally or intraperitoneally. In this study, we proposed to assess the safety and efficacy of the intravitreal injection of DHA in an age-related macular degeneration (AMD) rat model. Different concentrations of DHA were injected into the vitreous body. Histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis showed that there was no difference in thickness, observable structure, or apoptosis among the untreated, normal saline, and DHA groups (0.2, 1.0, 5.0 and 10µg). However, GFAP expression was increased in the 10µg group. To investigate whether intravitreal injection of DHA could protect photoreceptors, we developed a NaIO3-induced retinal damage model in adult rats. Decreases in deformation and thickness were observed in the outer nuclear layer (ONL) after NaIO3 administration but were improved with DHA injection. The NaIO3 group showed a substantial reduction in the number of nuclei in ONL, whereas the DHA group showed an increase. Additionally, significant increases in SOD activity and Nrf2 expression were observed after DHA injection; GFAP and NF-κB expression levels were markedly decreased by DHA injection. Moreover, Western blotting showed that Bax, cleaved caspase-3 and CHOP were notably increased in the NaIO3 group but were significantly decreased by DHA injection. Collectively, intravitreal injection of DHA is safe and effective in select doses in a NaIO3-induced AMD rat model. The current results suggest that intravitreal injection of DHA may be a new avenue for the treatment of AMD.

Effects of GSK2606414 on cell proliferation and endoplasmic reticulum stress­associated gene expression in retinal pigment epithelial cells.

GSK2606414 is a novel, highly selective inhibitor of protein kinase R­like endoplasmic reticulum kinase (PERK). GSK2606414 and its analogues have recently been demonstrated to delay tumor growth and prevent neurodegeneration. The present study investigated the effects of GSK2606414 on proliferation, apoptosis, and the expression of activating transcription factor 4 (ATF4), CCAAT/enhancer­binding protein homologous protein (CHOP) and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under endoplasmic reticulum (ER) stress. ARPE­19 human RPE cells were treated with 0.01­50 µM GSK2606414, and ER stress was induced by thapsigargin (TG) treatment. Cell proliferation was assessed using the Cell Counting kit­8 cell viability assay. Apoptosis was detected by Annexin­V/propidium iodide double staining using flow cytometry. Western blot analysis was used to measure eukaryotic initiation factor 2α (eIF2α) phosphorylation levels. ATF4, CHOP and VEGF mRNA expression levels were assessed using reverse transcription­quantitative polymerase chain reaction. GSK2606414 treatment inhibited RPE cell proliferation in a dose­dependent manner, however it did not induce apoptosis. In addition, GSK2606414 treatment inhibited eIF2α phosphorylation and reduced CHOP and VEGF mRNA expression levels in RPE cells under TG­induced ER stress. To the best of our knowledge, the present study is the first to demonstrate that GSK2606414 has a potential antiproliferative effect in RPE cells in vitro. This effect appeared to be achieved via inhibition of the PERK/ATF4/CHOP signaling pathway and suppression of VEGF expression levels.

Wnt Regulates Proliferation and Neurogenic Potential of Müller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas.

In cold-blooded vertebrates such as zebrafish, Müller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of ß-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3ß stabilizes ß-catenin and activates MG proliferation. Downstream of Wnt, ß-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes ß-catenin-mediated effects on MG proliferation, and Lin28 gene transfer stimulates MG proliferation. We further demonstrate that let-7 miRNAs are critically involved in Wnt/Lin28-regulated MG proliferation. Intriguingly, a subset of cell-cycle-reactivated MGs express markers for amacrine cells. Together, these results reveal a key role of Wnt-Lin28-let7 miRNA signaling in regulating proliferation and neurogenic potential of MGs in the adult mammalian retina.

Propofol Decreases Endoplasmic Reticulum Stress-Mediated Apoptosis in Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD) is the major cause of loss of sight globally. There is currently no effective treatment available. Retinal pigment epithelial (RPE) cells are an important part of the outer blood-retina barrier and their death is a determinant of AMD. Propofol, a common clinically used intravenous anesthetic agent, has been shown to act as an efficacious neuroprotective agent with antioxidative and anti-inflammatory properties in vivo and in vitro. However, little is known about its effects on RPE cells. The purpose of our research was to investigate whether propofol could protect RPE cells from apoptosis through endoplasmic reticulum (ER) stress-dependent pathways. To this end, prior to stimulation with thapsigargin (TG), ARPE-19 cells were pretreated with varying concentrations of propofol. A protective effect of propofol in TG-treated ARPE-9 was apparent, TUNEL and flow cytometric assays showed decreased apoptosis. We further demonstrated that propofol pretreatment attenuated or inhibited the effects caused by TG, such as upregulation of Bax, BiP, C/EBP homologous protein (CHOP), active caspase 12, and cleaved caspase 3, and downregulation of Bcl2. It also decreased the TG-induced levels of ER stress-related molecules such as p-PERK, p-eIF2α, and ATF4. Furthermore, it downregulated the expression of nuclear factor κB (NF-κB). This study elucidated novel propofol-induced cellular mechanisms for antiapoptotic activities in RPE cells undergoing ER stress and demonstrated the potential value of using propofol in the treatment of AMD.

Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis.

Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin­induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS­induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick­end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription­quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC­1 and ICAM­1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl­1 expression levels were observed. In conclusion, roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU.

Radial Retinotomies with Endodiathermy for Severe Proliferative Vitreoretinopathy: Short-Term Results.

Purpose. Retinal redetachment of silicone oil-filled eyes continues to be a frustrating condition that typically requires retinectomy. We proposed radial retinotomy as a potentially less invasive surgery. Here, we preliminarily explored its feasibility, efficacy, and safety. Methods. Totally 9 eyes of 9 consecutive patients were included in a prospective noncomparative trial. A series of retinotomies were created by endodiathermy in a radial pattern to relax the foreshortened retina. The eye was refilled with fresh silicone oil. The treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp microscopy, and fundus photography during a 6-month observation period. Results. The procedure was completed in an average of 28 minutes from silicone oil removal to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9 eyes (78%) exhibited retinal reattachment. On average, VA was significantly improved within the first 2 weeks (P = 0.02) and remained stable for the following 6 months. The change in intraocular pressure was not significant (P = 0.76), and no adverse event was observed (0%). Conclusion. Radial retinotomies with endodiathermy were shown to be feasible, effective, and safe in selected cases of inferior contracted retina without vitreous base fibrosis over a 6-month observation period. This trial is registered with NCT02201706.

Surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy combined with lensectomy for glaucomatous eyes with extremely shallow anterior chamber and cataract.

BACKGROUND: Glaucoma combined with an extremely shallow anterior chamber and cataracts remains as a complex condition to deal with. And the emergence of microincision vitrectomy surgery (MIVS) system may provide an ideal option for the treatment of that. We report a clinical study of surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy (PPV) combined with lensectomy in the treatment of glaucomatous eyes with extremely shallow anterior chamber and cataract. METHODS: Prospective, nonrandomized and noncomparative case series study. Consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited to have combined surgeries of 23-gauge transconjunctival pars plana vitrectomy and lensectomy. The main outcomes were best corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber depth (ACD), number of anti-glaucoma medications and surgery-associated complications. RESULTS: Seventeen consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited. The mean follow-up was 21.2 ± 8.8 months. Postoperatively, there was no significant improvement of BCVA (P = 0.25). The mean intraocular (IOP) decreased significantly from 43.14 ± 6.53 mmHg to 17.29 ± 1.80 mmHg (P < 0.001), and the mean depth of anterior chamber increased significantly from 0.507 ± 0.212 mm to 3.080 ± 0.313 mm (P < 0.001). The mean number of anti-glaucoma medications decreased from 4.1 ± 0.8 to 0.6 ± 0.8 (P < 0.001). No severe vision-threatening intra- or post-operative complications occurred. CONCLUSIONS: Glaucoma with an extremely shallow anterior chamber and cataract can be managed well with the combined surgeries of 23-gauge pars plana vitrectomy and lensectomy. The surgical procedure is an effective and safe method to resolve the pupillary block and deepen the anterior chamber.

A study of the dexamethasone sodium phosphate release properties from a periocular capsular drug delivery system.

The aim of this study was to investigate whether a periocular capsular drug delivery system (DDS) can release dexamethasone sodium phosphate (DEXP) in vitro and in vivo to the posterior segment of rabbit's eye. In vitro, the periocular capsular DDS containing 2 mg/ml or 5 mg/ml DEXP was immersed in modified Franz diffusion cell. Four-hundred microliters of liquid was aspirated at 0.5, 1, 2, 4, 8, 24 and 48 h for determination. In vivo, the DEXP-filled periocular capsular DDS was implanted into the sub-Tenon's sac of the New Zealand rabbit. DEXP concentration at the serum aqueous humor, cornea, iris, lens, ciliary body, vitreous, retina, choroids and sclera was quantified at 1, 3, 7, 14, 28 and 56 d after implantation. The DEXP concentration was determined by ultra-performance liquid chromatography-tandem mass spectrometry. In vitro, the periocular capsular DDS released the DEXP in time-dependent manner from 1/2 to 48 h. In vivo, the concentrations of the DEXP at the retina, choroids, ciliary body and iris were 123.11 (91.23, 732.61) ng/g, 362.46 ± 330.46 ng/g, 71.64 (71.35, 180.21) ng/g and 192.50 ± 42.66 ng/g, respectively, at 56 d after implantation. Minimal DEXP was found in the aqueous, serum and vitreous. Our results demonstrated that DEXP could be sustained released from the periocular capsular DDS, which indicated that the periocular capsular DDS might be a potential candidate of transscleral drug delivery for the management of posterior segment diseases.

A machine-independent method to have active removal of 5,000 centistokes silicone oil using plastic infusion tube and 23-gauge microcannulas.

BACKGROUND: To describe one modified method of having machine-independent removal of 5,000 centistokes silicone oil through 23-gauge trocar-cannulas. METHODS: Consecutive patients with silicone oil tamponade for more than four months and with complete retinal reattachment were included. Two 23-gauge trocars were used to make sclerotomies while the microcannulas remained in situ for intravitreous infusion and silicone oil drainage. A short section of infusion tube was connected with a 10 ml syringe's needle adapter. The other side was attached to the conjunctiva surface and covered the cannula's cap inside to form a closed space for silicone oil drainage. The main outcomes were duration for complete removal of silicone oil and intra- and postoperative complications. RESULT: There were totally twenty cases (20 eyes) included. The mean time for draining out the silicone oil was 4.54 ± 0.78 minutes. Intraoperatively, flute needle was introduced additionally in seven cases to achieve complete removal. No cases experienced postoperative visual acuity deterioration or refractory hypotony. No significant residual oil bubbles were observed. No retinal redetachment occurred throughout the follow-ups. CONCLUSION: The modified method of using an infusion tube and 23-gauge trocar-cannulas can achieve quick and complete removal of high viscosity silicone oil.

A SURGICAL APPROACH TO LARGE SUBRETINAL HEMORRHAGE USING PARS PLANA VITRECTOMY AND 360° RETINOTOMY.

PURPOSE: To evaluate the surgical approach of pars plana vitrectomy combined with 360° retinotomy and silicon oil tamponade in the treatment of patients with large subretinal hemorrhage. METHODS: Prospective, nonrandomized, and noncomparative case series study. Consecutive patients with breakthrough vitreous hemorrhage and massive subretinal hemorrahge were recruited to have combined surgery of pars plana vitrectomy with 360° retinotomy and silicone oil temponade. The main outcomes were best-corrected visual acuity, retina status, and postoperative complications. RESULTS: Twenty-one patients (21 eyes) were included. The mean follow-up was 19.9 ± 7.4 months. The mean preoperative thickness of subretinal hemorrhage was 4.25 ± 0.69 mm. All the patients were observed to have choroidal neovascularization during the surgical procedure. The mean logarithm of the minimum angle of resolution best-corrected visual acuity (Snellen equivalent) significantly improved from preoperatively 2.64 (hand movement) to 1.73 (7/400), 1.50 (6/200), 1.51 (6/200), and 1.45 (7/200) at 1 month, 3 months, 6 months after the initial surgery, and final follow-up. Postoperative complications included temporary higher intraocular pressure, silicone oil emulsification, lens opacification, epimacular membrane, retinal pigment epithelium loss, and subretinal fibrosis. At the end of the follow-up, retinas were all reattached without any recurrence of choroidal neovascularization. CONCLUSION: Pars plana vitrectomy combined with retinotomy and silicone oil tamponade is effective for eyes with breakthrough vitreous hemorrhage and massive subretinal hemorrahge.