Age is an important risk factor for primary glaucoma. While the specific mechanism of primary glaucoma remained unclear, the change of ocular anatomy, the disturbance of aqueous humor balance, the change of ocular biomechanics and the disorder of neurometabolism contribute to the occurrence and development of primary glaucoma. This paper reviewes the latest studies on the correlation between age and the risk factors of glaucoma in the above four aspects, so as to provide some references for the in-depth discussion of the pathophysiology of primary glaucoma, and advancement on diagnosis, treatment and research of primary glaucoma.

目的探索线粒体相关基因组的变异是否与正常眼压性青光眼(NTG)相关。方法抽取NTG患者、高眼压性原发性开角型青光眼(HTG)患者和年龄相关性白内障(ARC)患者的外周静脉血样本各10例,提取基因组DNA并构建测序文库。使用靶向二代测序技术检

年龄是原发性青光眼重要的危险因素。目前原发性青光眼的具体发生机制尚未阐明,其中眼球解剖学因素、房水动力学因素、眼球生物力学因素和神经代谢因素随年龄改变,从不同层面促成了原发性青光眼的发生和发展。本文汇总国内外有关年龄与

PURPOSE. The angiopoietin-1 (ANG1)-TIE signaling pathway orchestrates the development and maintenance of the Schlemm's canal (SC). In this study, we investigated the impact of adeno-associated virus (AAV)-mediated gene therapy with cartilage oligomeric matrix protein-ANG1 (COMP-ANG1) on trabecular outflow pathway.METHODS. Different serotypes of AAVs were compared for transduction specificity and efficiency in the anterior segment. The selected AAVs encoding COMP-ANG1 or ZsGreen1 (control) were delivered into the anterior chambers of wild-type C57BL/6J mice. The IOP and ocular surface were monitored regularly. Ocular perfusion was performed to measure the outflow facility and label flow patterns of the trabecular drainage pathway. Structural features of SC as well as limbal, retinal, and skin vessels were visualized by immunostaining. Ultrastructural changes in the SC and trabecular meshwork were observed under transmission electron microscopy.RESULTS. AAV-DJ could effectively infect the anterior segment. Intracameral injection of AAV-DJ.COMP-ANG1 lowered IOP in wild-type C57BL/6J mice. No signs of inflammation or angiogenesis were noticed. Four weeks after AAV injection, the conventional outflow facility and effective filtration area were increased significantly (P = 0.005 and P = 0.04, respectively). Consistently, the area of the SC was enlarged (P < 0.001) with increased density of giant vacuoles in the inner wall (P = 0.006). In addition, the SC endothelia lay on a more discontinuous basement membrane (P = 0.046) and a more porous juxtacanalicular tissue (P = 0.005) in the COMP-ANG1 group.CONCLUSIONS. Intracamerally injected AAV-DJ.COMP-ANG1 offers a significant IOPlowering effect by remodeling the trabecular outflow pathway of mouse eyes.

Background Primary congenital glaucoma (PCG) is characterized by developmental abnormalities of the anterior chamber angle. Although several genes have been associated with PCG, pathogenic mutations could only be detected in about 20% of Chinese patients. GLC3B (1p36.2-36.1) and GLC3C (14q24.3) loci were previously identified in PCG pedigrees via linkage analysis. However, no causative genes were reported in these loci. This study was designed to search for novel PCG-related genes in these genetic regions. Materials and methods DNA samples from 100 PCG patients and 200 normal controls were pooled and sequenced using a customized panel of 133 positional candidate genes located around GLC3B and GLC3C loci (+/- 1Mb). PCG-related genes were prioritized by the distribution of variants between patients and controls. Confirmation of selected variants and co-segregation analysis were performed using Sanger sequencing. Results Patient and control group contained 116 and 147 rare variants respectively after screening. Three genes (ZC2HC1C, VPS13D, and PGF) were prioritized according to the distribution of variants between the two groups. Rare variants of PGF were only identified in PCG patients. Conclusions To the best of our knowledge, this is the first study aiming at exploring novel PCG-related genes at GLC3B and GLC3C loci. Our preliminary results suggest that there are potential associations between ZC2HC1C, VPS13D, PGF, and PCG. However, larger cohort studies and functional assays are required to provide further evidence for the proposed genotype-phenotype association.

青光眼是不可逆性致盲性眼病,中国是青光眼患者人数最多的国家。小梁网(TM)是前房角处由胶原纤维构成的网状结构,它是眼房水排出的重要通路,该处的病理性改变可升高眼内压,导致青光眼的发生。近年来,不少研究聚焦于微小核糖核苷酸(miRNA

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.

Background: To compare the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) and Kahook Dual Blade (KDB) excisional goniotomy in patients with uncontrolled juvenile open-angle glaucoma (JOAG).Methods: Thirty-three patients (46 eyes) were included in this single-center, retrospective, comparative study and treated with GATT (36 eyes) or KDB goniotomy (13 eyes). Intraocular pressure (IOP), number of glaucoma medications, adverse events, and additional anti-glaucoma procedures were collected during pre- and postoperative visits. Surgical success was defined as 6 mmHg <= IOP <= 18 mmHg and >= 20% IOP reduction from baseline with (partial success) or without (complete success) IOP-lowering medications.Results: The mean +/- SD preoperative IOP was 30.48 +/- 12.9 mmHg and 26.08 +/- 13.1 mmHg (P = 0 .1 64) on 3.71 +/- 0.46 and 3.08 +/- 0.86 (P = 0 .0 23) glaucoma medications in GATT and KDB group, respectively. At 3 months, the mean +/- SD IOP was 15.48 +/- 5.93 mmHg and 20.0 +/- 10.8 mmHg after GATT and KDB, respectively (P= 0.072). The percentage of IOP lowering from baseline was 44.4 in the GATT group and 14.1 in the KDB group (P = 0.011). The mean reduction in medications was 2.6 +/- 1.7 and 0.8 +/- 1.2 three months after GATT and KDB, respectively (P<0.001). Cumulative proportion of partial and complete success were 65.6 and 44.7% in the GATT group, 30.8 and 15.4% in the KDB group at 6 months. Additional procedures were required in 13.9% of cases after GATT and in 61.5% after KDB (P= 0.001). Patients in the GATT group with prior anti-glaucoma procedures and postoperative IOP spikes were more likely to fail, while those with complete trabeculotomy had a better prognosis.Conclusions: Reduction of lOP and medications were greater after GATT in uncontrolled JOAG eyes. Whereas, more additional lOP-lowering procedures were required after KDB goniotomy.