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.

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.

目前对于原发性开角型青光眼发病机制的探索，仍在不断进行中。小梁网途径是调节眼内压的重要调节区域，针对于小梁网途径的房水流出调节机制与药物仍在不断开发，是青光眼降眼压治疗中的重要研究领域。.Schlemm(SC)管内皮细胞是小梁网流出途径阻力最大的位置，课题组发现了小分子核酸miR-21-5p促进房水静脉细胞通透性增加，显著提高小鼠眼球内小梁网房水流出率、降低眼内压，并且其调节作用与多项调节细胞通透性、细胞外基质重塑和细胞骨架相关的信号通路相关，并且在原发性开角型青光眼患者房水中,miR-21-5p有一定趋势的降低，提示miR-21-5p可能是调控眼内压的靶点。.基于项目前期工作经验，课题组探索了作用于小梁网途径的核酸载体：AAV-DJ(腺相关病毒DJ型)与聚多巴胺—聚乙烯亚胺纳米颗粒(PDA/PEI NPs)在体转染的安全性可行性，并评估了用于载入目的核酸降低眼压的有效性，为针对小梁网途径的在体核酸转染提供了参考方案。.除上述探索外，项目组进一步通过对青光眼细胞模型的全转录组学联合分析，进一步寻找与小梁网途径流出通道阻力相关的重要分子与机制，聚焦调节SC 生物力学的靶点。此外，对于影响小梁网途径发育于维持的重要信号通路也进行了相关探索，并在国人的临床样本中多角度验证了该通路基因突变的致病性。.综上，本项目探索了在小梁网房水流出途径中的调节功能与机制的重要分子，以及作用与小梁网房水流出通路的核酸载体，对于针对小梁网途径的机制研究和治疗策略提供更丰富的信息和参考。本项目已发表并标注本课题的SCI论文共11篇，国内核心期刊6篇，获得国家发明专利授权2项。

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.