PACAP38调控TRPC6表达对糖尿病视网膜病变大鼠的保护作用

目的探讨垂体腺苷酸环化酶激活肽-38(pituitary adenylate cyclase-activating peptide-38,PACAP38)在糖尿病视网膜病变(diabetic retinopathy,DR)过程中的视网膜保护是否由瞬时受体电位通道6(TRPC6)介导。方法将30只SD大鼠随机分为空白对照组和STZ组,每组15只。经单次腹腔注射链脲佐菌素(streptozotocin,STZ)诱发大鼠糖尿病动物模型。根据不同的干预方式,在注射STZ 2周后,一次性向大鼠一眼玻璃体内注射100μmol·L^-1 PACAP38(STZ+PACAP38组),另一眼注射等量的PBS作为对照(STZ对照组)。采用Western blot和免疫组织化学分析视网膜组织中瞬时受体电位离子通道蛋白6(transient receptor potential channel 6,TRPC6)的表达情况。利用光学相干断层扫描检测各组大鼠的视网膜厚度。将视网膜神经节细胞系RGC-5细胞暴露于高血糖和低氧环境,分别给予PACAP38、TRPC6通道激动剂(OAG)、PAC1受...     

青光眼神经保护治疗研究进展

目前认为青光眼是一种由眼压升高在内的多重危险因素诱导的视神经变性疾病 ,其病理基础是视网膜神经节细胞及其轴突的进行性丢失。神经保护治疗是一种通过阻止神经元死亡治疗神经系统病变的新策略。本文从实验技术、理论基础、治疗手段等方面 ,总结了目前神经保护治疗青光眼的研究进展。     

Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis

AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats. METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically. RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P<0.05). The neuroprotective activity of edaravone was found to be more influential by administration at the start of the glaucoma process. Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups (Bonferroni, P<0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group (Bonferroni, P<0.05). CONCLUSION: Systemic administration of Edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.     

青光眼药物治疗的进展

随着人们对青光眼治疗机制研究的深入,涌现了不少新的抗青光眼药物。最经典的治疗方法仍然是降低眼压。新的降眼压药物可能通过以下途径发挥作用：①诱导金属蛋白酶的产生;②使小梁网细胞收缩;③抑制房水的生成;④激活CB-1受体等。另一类重点研究的药物,可增加眼部血流,尤其是视网膜和视神经的血流。对于正常眼压或低眼压性青光眼患,不依赖于眼压改变而增加血流的药物有非常重要的临床意义。神经保护药物,是近年来才出现的新的青光眼治疗方法。虽然其研究历史很短,但包含了多种类型的药物。其中包括NMDA受体阻断剂,神经营养因子,可诱导的一氧化氮合成酶抑制剂,能抑制细胞调亡的药物,保护性自身免疫治疗,干细胞治疗等等。所有的抗青光眼药物都只能稳定病情,而不能治愈疾病,因此理想的药物应该具有较高的性价比。     

New ideas for medical therapy of glaucoma in the future

New drugs are developed rapidly with novel ideas of action mechanisms for the treatment of glaucoma. The most classic drugs under development are to lower the intraocular pressure (IOP). New agents were invented to lower the IOP through ① induction of metalloproteinases (MMPs), ② contraction of trabecular meshwork cells, ③ inhibition of aqueous humor secretion, and ④ activation of CB-1 receptor, The second class of drugs under development is intended to improve the ocular blood flow (OBF), particularly in retina and optic nerve head (ONH). Drugs that improve the OBF irrespective of the IOP changes could be quite useful for the treatment of normal tension or low-tension glaucoma. Neuroprotection is the latest developed mechanisms of glaucoma treatment. Although the history of neuroprotection research is very short, there are many agents under investigation in this class. They include ① blockade of N-methyl-D-aspartate receptor, ② neurotrophic agents, ③ inhibition of inducible nitric oxide synthases (iNOS), ④ inhibition of apoptosis, ⑤ protective autoimmunity, ⑥ stem cell therapy, and so on. Since all drugs for glaucoma treatment are used to stabilize the disease rather than to cure it, it is critical that an ideal drug with high therapeutic index and low cost price should be invented.     

TRPV4在眼病理生理功能中的研究进展

瞬时受体电位香草醛受体4(TRPV4)是一种非选择性阳离子通道,负责感知细胞肿胀、温度、机械牵张、剪切应力和渗透压的变化,通过调节跨膜钙信号进而影响基因表达、细胞形态和细胞骨架等构建。TRPV4在全身广泛表达。在眼内,TRPV4在角膜、晶状体、睫状体、小梁网和视网膜等组织均有功能性表达。本文就TRPV4在眼内各个组织中的表达及生理病理功能方面进行阐述。随着TRPV4在眼部病理生理功能中的深入研究,TRPV4在角膜损伤修复、青光眼及视网膜血管生成方面可能成为潜在的新兴药物靶点,但仍需进一步的深入研究。     

Endoscopic cyclophotocoagulation for the treatment of glaucoma: an Asian experience

Background: To describe the efficacy and safety of endoscopic cyclophotocoagulation in Asian patients with glaucoma. Methods: Retrospective case series. Consecutive cases of endoscopic cyclophotocoagulation performed by one surgeon during the study period were included. Patients' records were reviewed for clinical and demographic factors, treatments, intraocular pressure (IOP), visual acuity and any complications. Results: Twenty‐nine eyes of 29 patients were treated. Their mean age was 73.6 ± 9.4 years. The mean follow‐up duration was 15.9 ± 8.9 months. Eleven patients had primary open‐angle glaucoma, two normal tension glaucoma, six chronic angle‐closure glaucoma, five neovascular glaucoma, four secondary open‐angle glaucoma and one secondary angle‐closure glaucoma. Twenty patients had endoscopic cyclophotocoagulation combined with cataract surgery. Mean pretreatment IOP was 21.8 ± 6.6 mmHg. Mean post‐treatment IOP at 18 months (n = 17) was 16.2 ± 4.1 mmHg (P = 0.02) and 17.9 ± 4.9 mmHg (P = 0.18) at 24 months (n = 10). The mean number of anti‐glaucoma medications pretreatment was reduced from 2.0 ± 1.0 to 0.9 ± 0.9 at 18 months post‐treatment (P = 0.04) and 1.2 ± 0.8 at 24 months (P = 0.13). The overall success rate based on IOP reduction of 20% or greater at last follow‐up was 48.3%. Visual acuity was reduced in five eyes. Complications included one case each of hyphaema, bullous keratopathy, transient pigment dispersion and iris burn. Conclusion: Endoscopic cyclophotocoagulation may have a treatment role in Asian patients with glaucoma. The success rate appears poorer than previously reported in Caucasian populations. The treatment effect appeared to wane between 18 and 24 months post‐treatment.     

Neurotrophic factor delivery as a protective treatment for glaucoma

Glaucoma is a progressive optic neuropathy and a major cause of visual impairment worldwide. Neuroprotective therapies for glaucoma aim to ameliorate retinal ganglion cell degeneration through direct or indirect action on these neurons. Neurotrophic factor (NTF) delivery is a key target for the development of potential neuroprotective glaucoma treatments. This article will critically summarize the evidence that NTF deprivation and/or dysfunction plays a role in the pathogenesis of glaucoma. Experimental support for the neuroprotective potential of NTF supplementation in animal models of glaucoma will be reviewed, in particular for brain-derived neurotrophic factor, ciliary neurotrophic factor, and glial cell line-derived neurotrophic factor. Finally, the challenges of clinical translation will be considered with an emphasis on the most promising NTF delivery strategies including slow-release drug delivery, gene therapy, and cell transplantation.     

Nutritional supplementation in the treatment of glaucoma: A systematic review

Current treatment strategies for glaucoma are limited to halting disease progression and do not restore lost visual function. Intraocular pressure is the main risk factor for glaucoma, and intraocular pressure–lowering treatment remains the mainstay of glaucoma treatment, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. We review the literature to determine whether nutritional interventions intended to prevent or delay the progression of glaucoma could prove to be a valuable addition to the mainstay of glaucoma therapy. A total of 33 intervention trials were included in this review, including 21 randomized controlled trials. These suggest that flavonoids exert a beneficial effect in glaucoma, particularly in terms of improving ocular blood flow and potentially slowing progression of visual field loss. In addition, supplements containing forskolin have consistently demonstrated the capacity to reduce intraocular pressure beyond the levels achieved with traditional therapy alone; however, despite the strong theoretical rationale and initial clinical evidence for the beneficial effect of dietary supplementation as an adjunct therapy for glaucoma, the evidence is not conclusive. More and better quality research is required to evaluate the role of nutritional supplementation in glaucoma.     

The cellular mechanism underlying neuronal degeneration in glaucoma: Parallels with Alzheimer's disease

Evidence is presented that the characteristic pattern of neuronal degeneration associated with glaucoma is due to a combination of the persistent physical damage to axons at the level of the lamina cribrosa and the associated neuronal reaction to this kind of trauma. The class of neuronal cytoskeletal proteins known as the neurofilament triplet are crucially involved in the reaction to physical damage and the selective localization of these proteins to larger retinal ganglion cells may underlie their susceptibility to eventual degeneration. The appearance of glaucoma-like neuronal pathology in Alzheimer's disease may follow the reaction of neurofilament-containing retinal ganglion neurons to persistent damage to their axons by β-amyloid plaque formation in subcortical visual centres.     

血清及房水中VEGF、IL-6水平与新生血管性青光眼的相关性研究

目的测定新生血管性青光眼（NVG）患者血清及房水中血管内皮生长因子（VEGF）、白细胞介素-6（IL-6）的水平,探讨VEGF、IL-6在NVG发生发展中的作用。方法选取NVG患者20例（20只眼）作为实验组（A组）,原发性慢性闭角型青光眼患者（B组）、老年性白内障患者（C组）各20例（20只眼）作为对照组。采集3组患者血清及房水标本,通过双抗体夹心酶联免疫吸附试验（ELISA法）分别检测血清与房水中VEGF、IL-6的水平。结果 （1）A组房水中VEGF、IL-6的水平（1336.80±70.15）pg/ml、（691.15±50.09）pg/ml明显高于B组（311.60±31.06）pg/ml、（168.25±11.95）pg/ml和C组（165.75±13.95）pg/ml,（92.10±9.59）pg/ml,3组间两两比较,差异均具有统计学意义（F=4019.334,P〈0.01;F=2275.019,P〈0.01）。A组血清中VEGF、IL-6的水平（545.40±155.49）pg/ml、（291.35±22.66）pg/ml高于B组（321.15±52.57）pg/ml、（104.35±13.21）pg/ml和C组（176.30±20.38）pg/ml、（87.00±12.70）pg/ml,3组间两两比较,差异均具有统计学意义（F=75.940,P〈0.01;F=906.947,P〈0.01）。（2）A组房水中VEGF与IL-6的水平呈显著的正相关性,差异具有统计学意义（r=0.857,P〈0.01）。其余各组标本中无显著的相关性（P〉0.05）。结论 NVG患者房水及血清中VEGF、IL-6的水平明显高于对照组,且房水中二者水平呈明显正相关,提示在NVG病理机制过程中,VEGF、IL-6作为促血管生成因子,相互促进、相互影响,共同导致了NVG的发生和发展。     

Cod liver oil: a potential protective supplement for human glaucoma

Glaucoma is one of the leading causes of visual impairment and blindness. Improved knowledge of the pathogenesis of this disease has allowed the exploration of new therapeutic methods. In general, elevated intraocular pressure (IOP), oxidative stress, and vascular insufficiency are accepted as the major risk factors for the progression of glaucoma. Many natural compounds have been found beneficial for glaucoma. Nutritional therapies are now emerging as potentially effective in glaucomatous therapy. One nutritional supplement with potential therapeutic value is cod liver oil, a dietary supplement that contains vitamin A and omega-3 polyunsaturated fatty acids (PUFAs). Vitamin A is important for preserving normal vision and it is a well-known antioxidant that prevents the oxidative damage that contributes to the etiology and progression of glaucoma. Vitamin A is also a crucial factor for maintaining the integrity of conjunctival and corneal ocular surfaces, and preventing the impairment of ocular epithelium caused by topical antiglaucomatous drugs. Omega-3 fatty acids are beneficial for glaucoma patients as they decrease IOP, increase ocular blood flow, and improve optic neuroprotective function. In this article, we propose that cod liver oil, as a combination of vitamin A and omega-3 fatty acids, should be beneficial for the treatment of glaucoma. However, further studies are needed to explore the relationship between cod liver oil and glaucoma.     

Hippocrates to Duke‐Elder: an overview of the history of glaucoma

Objective : To briefly trace the history of the diagnosis, understanding and treatment of glaucoma. Method : Selective review of the early literature on glaucoma to the mid‐20th century.     

TRPV4在青光眼性视神经病变中的研究进展

青光眼性视神经病变(GON)是青光眼治疗难点所在。近年来,关于GON的发病机制提出了多种学说,但其中任何一种均无法解释所有类型青光眼造成的视神经病变原理,使得该病在临床治疗中顾此失彼,且不利于早期干预。最新研究发现,存在于视网膜中的瞬时受体电位通道香草酸亚家族4(TRPV4)在GON多种发病机制中均占有重要地位。本文将对TRPV4及其在GON发生发展过程中所发挥的作用作一综述,以期为GON的多种机制学说寻找一共同“连接点”,这将有助于对该病的进一步认识和临床治疗。     

There is insufficient evidence to recommend lens extraction as a treatment for primary open-angle glaucoma: an evidence-based perspective

Cataract extraction in primary open-angle glaucoma has not been thought to provide a clinically useful or predictable decrease in IOP. This concept has now been challenged, with the opposite belief being promulgated: namely, that lens exchange should be considered as treatment for glaucoma. This revelation could bring a significant change in the glaucoma treatment paradigm. There are no randomised controlled trials to guide the role of lens extraction in primary open-angle glaucoma. The available evidence suggests at most a modest reduction in IOP from cataract extraction - greater in the presence of pseudoexfoliation - which is likely to be of marginal benefit, and only in milder forms of open-angle glaucoma. There is currently no evidence of any quality to suggest that lens extraction routinely represents a clinically useful treatment for primary open-angle glaucoma.     

Anterior chamber depth and primary angle-closure glaucoma: an evolutionary perspective

Anterior chamber depth is an inheritable trait which is affected by age, gender and race. Over 30 years ago, Alsbirk proposed that the shallow anterior chamber, which was typical of the Greenlandic Inuit, and which brings the iris in proximity to the cornea, may have evolved as a thermoregulatory adaptation to resist corneal freezing. Here, this hypothesis is revisited. Recent population genetic data which provide evidence for migration patterns of early humans are discussed and the notions of natural selection and ocular adaptation to cold climates are considered. Problems with the hypothesis are examined, but the idea that the shallow anterior chamber has a thermoregulatory role appears sound and suggests that shallow anterior chambers may have evolved in Homo sapiens living in north-east Asia during the last Ice Age.     

Visual evoked cortical potential to paracentral retinal stimulation in chronic glaucoma,ocular hypertension,and an age-matched group of normals

Visual evoked cortical potentials (VECPs) to midperipheral stimulation of the visual field were elicited in age-matched groups of patients with unilateral chronic simple glaucoma or ocular hypertension and normal subjects. With a multimodal stimulus approach comprising transient and steady-state pattern reversal and transient onset-offset VECPs, 82.1% of the glaucoma group and 50.9% of the ocular hypertensives revealed significant abnormalities (p < 0.01) in one or more of the electrophysiological features measured, i.e., latency, phase, amplitude, and contrast threshold.