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Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

High myopia (HM) is a leading cause of mid-way blindness with a high heritability in East Asia. Although only a few disease genes have been reported, a small proportion of patients could be identified with genetic predispositions. In order to expand the mutation spectrum of the causative genes in Chinese adult population, we investigated three genes, SLC39A5 , LEPREL1 and LRPAP1 , in a cohort of 187 independent Chinese patients with high myopia. Sanger sequencing was used to find possible pathogenic mutations, which were further screened in normal controls. After a pipeline of database and predictive assessments filtering, we, thereby, identified totally seven heterozygous mutations in the three genes. Among them, three novel missense mutations, c.860C > T, p.Pro287Leu and c.956G > C, p.Arg319Thr in SLC39A5 , c.1982A > G, p.Lys661Arg in LEPREL1 , were identified as potentially causative mutations. Additionally, the two heterozygous mutations (c.1582G > A, p.Ala528Thr; c.1982A > G, p.Lys661Arg) in one patient in LEPREL1 gene were reported in this study. Our findings will not only augment the mutation spectrum of these three genes, but also provide insights of the contribution of these genes to adult high myopia in Chinese. However, further studies are still needed to address the pathogenicity of each of the mutations reported in this study.

Retinal pigment epithelium (RPE) serves critical functions in maintaining retinal homeostasis. An important function of RPE is to degrade the photoreceptor outer segment fragments daily to maintain photoreceptor function and longevity throughout life. An impairment of RPE functions such as metabolic regulation leads to the development of age-related macular degeneration (AMD) and inherited retinal degenerative diseases. As substrate recognition subunit of a ubiquitin ligase complex, suppressor of cytokine signaling 2 (SOCS2) specifically binds to the substrates for ubiquitination and negatively regulates growth hormone signaling. Herein, we explore the role of SOCS2 in the metabolic regulation of autophagy in the RPE cells. SOCS2 knockout mice exhibited the irregular morphological deposits between the RPE and Bruch’s membrane. Both in vivo and in vitro experiments showed that RPE cells lacking SOCS2 displayed impaired autophagy, which could be recovered by re-expressing SOCS2. SOCS2 recognizes the ubiquitylated proteins and participates in the formation of autolysosome by binding with autophagy receptors and lysosome-associated membrane protein2 (LAMP-2), thereby regulating the phosphorylation of glycogen synthase kinase 3β (GSK3β) and mammalian target of rapamycin (mTOR) during the autophagy process. Our results imply that SOCS2 participates in ubiquitin-autophagy-lysosomal pathway and enhances autophagy by regulating GSK3β and mTOR. This study provides a potential therapeutic target for AMD.

Purpose. To report a new technique for sutureless intrascleral fixation of three-piece foldable intraocular lenses (IOLs) using 25-gauge trocars. Methods. We performed this technique on patients with insufficient posterior capsule support. Seventeen eyes from 15 patients with aphakia, dislocated IOL, or subluxated crystalline lens undergoing posterior chamber sutureless implantation of an IOL were studied. The haptics of the IOL were externalized using two 25-gauge forceps. The haptics were bended back (hook-like) into the vitreous cavity through a scleral incision made by using a 25-gauge trocar. And, IOL tilt was determined by using a slit lamp and UBM, and complications were recorded. Results. The IOLs were fixed with exact centration and axial stability. No wound leakage was reported even without the use of sutures. The mean best-corrected visual acuity (BCVA) was 0.82 logarithm of the minimum angle of resolution (logMAR) units preoperatively, and the mean BCVA was 0.44 logMAR units at the 6-month follow-up visit. No postoperative retinal detachment, endophthalmitis, IOL tilt or dislocation, or vitreous hemorrhage was noted. Conclusion. Sutureless intrascleral haptic-hook posterior chamber IOL implantation using 25-gauge trocars provides good IOL fixation with reliable wound closure without the use of sutures. This trial is registered with ChiCTR1800017436.

BackgroundPathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications.MethodsVH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis.ResultsBioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications.ConclusionsOur study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.

Purpose: Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can range from minor to severe. The surgery procedure of vitrectomy for symptomatic vitreous floaters is much simpler, mainly reflecting in the nonuse of sclera indentation, photocoagulation, and the apparently short surgery duration. The use of 27-gauge cannulae makes the puncture of the sclera minimally invasive. Hence, retrobulbar anesthesia, due to its rare but severe complications, seemed excessive for this kind of surgery. Method: Three cases of 27-gauge, sutureless pars plana vitrectomy for symptomatic vitreous floaters with topical anesthesia are reported. Results: The vitrectomy surgeries were successfully performed with topical anesthesia (proparacaine, 0.5%) without operative or postoperative complications. Furthermore, none of the patients experienced apparent pain during or after the surgery. Conclusion: Topical anesthesia can be considered for 27-guage vitrectomy in patients with symptomatic vitreous floaters.

Precursor messenger RNA (Pre-mRNA) splicing is an essential biological process in eukaryotic cells. Genetic mutations in many spliceosome genes confer human eye diseases. Mutations in the pre-mRNA splicing factor, RP9 (also known as PAP1), predispose autosomal dominant retinitis pigmentosa (adRP) with an early onset and severe vision loss. However, underlying molecular mechanisms of the RP9 mutation causing photoreceptor degeneration remains fully unknown. Here, we utilize the CRISPR/Cas9 system to generate both the Rp9 gene knockout (KO) and point mutation knock in (KI) ( Rp9 , c.A386T, P.H129L) which is analogous to the reported one in the retinitis pigmentosa patients ( RP9 , c.A410T, P.H137L) in 661 W retinal photoreceptor cells in vitro . We found that proliferation and migration were significantly decreased in the mutated cells. Gene expression profiling by RNA-Seq demonstrated that RP associated genes, Fscn2 and Bbs2 , were down-regulated in the mutated cells. Furthermore, pre-mRNA splicing of the Fscn2 gene was markedly affected. Our findings reveal a functional relationship between the ubiquitously expressing RP9 and the disease-specific gene, thereafter provide a new insight of disease mechanism in RP9 -related retinitis pigmentosa.

Background To compare the safety and efficacy of topical anesthesia versus retrobulbar anesthesia in 27-gauge pars plana vitrectomy (PPV) for vitreous floaters. Methods 30 patients with vitreous floaters were randomized into Group T (topical anesthesia, proparacaine eye drop) and Group R (retrobulbar anesthesia), and underwent 27-gauge PPV. A 5-point visual analogue pain scale (VAPS) was used to assess patients’ pain experience of anesthesia and surgery procedure (during surgery, 2 h and 1 day after surgery). Results The VAPS of anesthesia procedure was 1.27 ± 0.59 for patients in Group R, while it was all 0 for patients in Group T ( p  < 0.001). There was no significant difference for VAPS during surgery (Group T: 1.13 ± 0.74, Group R: 0.67 ± 0.62, p  = 0.67), 2 h (Group T: 0.80 ± 1.01, Group R: 0.67 ± 0.62, p  = 0.67) and 1 day (Group T: 0.20 ± 0.41, Group R: 0.27 ± 0.46, p  = 0.68) after surgery between these two groups. Only one patient (6.7%) in Group T required additional topical anesthesia during the surgery. Most of the patients reported the pain experience came from initial trocar insertion in both groups. None of the patients required post operative analgesia in both groups. No intraoperative or postoperative complications were noted in both groups. Conclusion This study suggested that topical anesthesia is a safe and effective anesthetic approach for patients with floaters who underwent 27-gauge PPV. Trial registration ClinicalTrials.gov NCT03049163 . Registered 8 February 2017.

Purpose. To report the safety and efficacy of adjustable postoperative position for rhegmatogenous retinal detachment (RRD). Methods. Retrospective review of 536 consecutive RRD eyes that underwent vitrectomy surgery for retina repair from year 2008 to 2014. The retinal breaks were divided into superior, lateral (nasal, temporal, and macular), and inferior locations, according to the clock of breaks. Patients with superior and lateral break location were allowed to have facedown position or lateral decubitus position postoperatively, while patients with inferior break location were allowed to have facedown position. Results. 403 eyes of 400 patients were included. The mean follow-up interval was 22.7 ± 21.3 months. The overall primary retinal reattachment rate was 93.3%. There were 24 (6.0%), 273 (67.7%), and 106 (26.3%) patients with superior, lateral, and inferior break location, respectively. The primary reattachment rate was 95.8%, 92.3%, and 95.3% accordingly. After further divided the break location into subgroups as a function of duration of symptom, postoperative lens situation, number of retinal breaks, and different vitreous tamponade, the primary reattachment rates were all higher than 82%. Conclusion. Adjustable postoperative positioning is effective and safe for RRD repair with different break locations. Choosing postoperative position appropriately according to retinal break locations could be recommended.

Purpose. To investigate the effect of menstrual cycle on perioperative bleeding of primary vitreoretinal surgery. Methods. Data on female patients who had vitrectomy surgery was retrospectively collected. Exclusion criteria were history of trauma, vitreous hemorrhage, previous vitreoretinal surgery, diabetic retinopathy, endophthalmitis, acute retinal necrosis, single vitreous opacity, and use of antiplatelet agents. Perioperative bleeding was defined as hemorrhage in the iris, vitreous, choroidal, retina, or subretina during surgery or up to one day postoperatively. 69 patients had surgery during the perimenstrual phase (group M, days 1–7 and days 21–28) and 86 during periovulatory phase (group O, days 8–20) were enrolled. Results. The proportion of operative bleeding in group M (14.5%) and group O (10.5%) was not found to be significantly different (p=0.45). No postoperative bleeding was recorded in both groups. The univariate odds ratio (OR) and 95% confidence interval (CI) of perimenstrual phase for operative bleeding were 0.69 (0.26–1.81). After adjusting for patients’ age, vitreoretinal diseases, and surgeons, the multivariate OR and 95% CI were 0.71 (0.27–1.86). Conclusion. This study suggests that the timing of the menstrual period does not affect perioperative bleeding for primary vitreoretinal surgery. Menstruation appears not to be a contraindication for vitreoretinal surgery.