糠尿病患者的眼动脉和视网膜中央动脉血流动力学改变

目的 :应用彩色多普勒显像 (colorDopplerflowimaging ,CDFI)检测糖尿病患者 ,以探讨其血液动力学变化 ,提供有参考价值的数据。方法 :应用CDFI检测了 3 0例糖尿病患者和 50例正常对照组的眼动脉、视网膜中央动脉的收缩期血流峰速、舒张末期流速、平均流速、血管阻力指数和搏动指数。结果 :糖尿病组与对照组比较有 /或无糖尿病视网膜病变 (diabeticretinopathy ,DR)OA和CRA的Vs、Vd降低 (P <0 0 5)、RI增加 (P <0 0 5)。结论 :糖尿病患者的OA和CRA血流速度降低 ,视网膜循环阻力升高 ,视网膜血液供应不良。     

糖尿病患者的眼动脉和视网膜中央动脉血流动力学改变

目的：应用彩色多普勒显像（ｃｏｌｏｒＤｏｐｐｌｅｒ ｆｌｏｗ ｉｍａｇｉｎｇ,ＣＤＦＩ）检测糖尿病患者,以探讨其血液动力学变化,提供有参考价值的数据。方法：应用ＣＤＦＩ检测了３０例糖尿病患者和５０例正常对照组的眼动脉、视网膜中央动脉的收缩期血流峰速、舒张末期流速、平均流速、血管阻力指数和搏动指数。结果：糖尿病组与对照组比较有／或无糖尿病视网膜病变（ｄｉａｂｅｔｉｃ ｒｅｔｉｎｏｐａｔｈｙ,ＤＲ）Ｏ     

The role of cytokines in the pathogenesis of diabetic retinopathy

PURPOSE: To investigate the role of cytokines and advanced glycation end products(AGEs) in the pathogenesis of diabetic retinopathy, we measured vascular endothelial growth factor(VEGF), interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-alpha), transforming growth factor-beta 1(TGF-beta 1), and pentosidine(an AGE) levels in aqueous, vitreous, and paired plasma obtained from diabetic patients. RESULTS: The aqueous levels of VEGF and IL-6 were positively correlated with the grade of clinical severity of diabetic retinopathy (both VEGF and IL-6, p < 0.001). Other cytokines and pentosidine levels were not significantly associated. The aqueous levels of VEGF and IL-6 were higher than the plasma levels(VEGF p = 0.02, IL-6 p < 0.001). CONCLUSION: Within the intraocular area VEGF and IL-6 are produced and participate in the pathogenesis of hyperpermeability of retinal vessels in preproliferative diabetic retinopathy.     

SIRT1在糖尿病视网膜病变发病机制中的作用

沉默信息调节因子1（silent information regulator1,SIRT1）属于第Ⅲll型组蛋白去乙酰化酶,与糖尿病视网膜病变发病相关.SIRT1可通过抑制炎性反应,抑制氧化应激对视网膜细胞的损害,影响血管内皮生长因子的生成,抑制视网膜细胞凋亡,从而影响糖尿病视网膜病变的发病及进展.目前已有数个白藜芦醇（SIRT1激动剂）制剂进入治疗2型糖尿病的临床试验阶段,其治疗效果还需进一步验证.     

Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina

The anti-inflammatory glucocorticoid, triamcinolone acetonide, is used clinically for the rapid resolution of diabetic macular edema. Osmotic swelling of glial cells may contribute to the development of retinal edema. Triamcinolone inhibits the swelling of retinal glial cells of diabetic rats. Here, we determined whether the effect of triamcinolone is mediated by a receptor-dependent mechanism. Hyperglycemia was induced in rats with streptozotocin injection. After 6-10 months, the swelling properties of glial cells in retinal slices upon hypotonic challenge were determined. Nucleotide-degrading ecto-enzymes were immunostained in retinal slices and glial cells. Hypotonic challenge did not change the size of glial cell bodies from control retinas but induced swelling of cells from diabetic animals. Triamcinolone inhibited glial cell swelling; this effect was prevented by a selective antagonist of adenosine A1 receptors, an inhibitor of nucleoside transporters, inhibitors of adenylyl cyclase and protein kinase A activation, and inhibitors of potassium and chloride channels. In diabetic (but not control) retinas, the effect of triamcinolone apparently involves extracellular nucleotide degradation. Glial cells from diabetic retinas displayed immunolabeling against nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) which was not observed in control retinas. The mRNA expression for NTPDase1 was significantly increased in the retina of diabetic rats. It is suggested that triamcinolone induces the release and formation of endogenous adenosine that subsequently activates A1 receptors resulting in ion efflux through potassium and chloride channels and prevention of osmotic swelling. Whereas adenosine is liberated via facilitated transport in control retinas, an extracellular formation of adenosine contributes to the effect of triamcinolone in diabetic retinas.     

The pathogenesis of early retinal changes of diabetic retinopathy

Recent successful trials of antibodies to vascular endothelial growth factor (VEGF) in diabetic retinopathy implicate this cytokine as a major cause of diabetic retinopathy (DR) and diabetic macular oedema (DME). The mechanisms which cause VEGF to be over-expressed to cause the vasculopathy are not entirely clear. This review explores the earliest changes to the retina in DR and the factors that predispose or prevent DR, including sleep apnoea, receptor degenerations laser treatment and VEGF polymorphism. The review also presents the evidence that retinal hypoxia, existing in the earliest stages, causes DR. This hypoxia is much increased by dark adaptation, indicating a new and possibly superior therapy.     

The role of blood pressure in glaucoma

Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow; however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.     

链脲佐菌素诱发糖尿病大鼠模型视网膜形态学改变的观察

目的 研究链脲佐菌素(streptozotocin,STZ)诱发SD大鼠糖尿病的视网膜形态学改变,为STZ诱发的糖尿病大鼠作为糖尿病视网膜病变动物模型提供依据.方法 20只成年SD大鼠随机分为2组,A组用STZ腹腔注射法诱发糖尿病,B组作为正常对照.用葡萄糖氧化酶法在建模后1 d、2 d、3 d、1周、2周、3周、4周连续测定大鼠血糖,在建模当天及建模后1周、2周、3周、4周用电子天平连续测量大鼠体质量,判断糖尿病发生的有效性和稳定性.通过临床和实验方法(包括裂隙灯检查,直接、间接眼底镜检查,4周时行组织切片、视网膜血管铺片、透射电镜等方法)检查大鼠眼前后节的病理改变.结果 A组大鼠血糖在注射STZ后1 d达到(33.9±1.7)mm01.L-1,在4周时达到(41.6±4.5)mmol.L-1,而B组始终低于16.7 mmoI.L-1.从建模之后,A组大鼠的体质量与B组相比,增长缓慢,有显著统计学意义.临床检查,A组1只糖尿病大鼠在4周时发生了白内障,B组大鼠眼前后节没有明显改变.发病4周时,组织学检查显示,A组大鼠视网膜厚度要薄于B组,透射电镜显示A组大鼠视网膜各层结构有明显的病理改变包括膜盘间隙扩大、排列紊乱、内外核层细胞疏松等,血管铺片显示4周A组大鼠视网膜毛细血管周细胞数量减少.结论 用STZ方法建立糖尿病模型是有效的,发病4周时糖尿病大鼠已经有较明显的视网膜形态学改变,能够作为糖尿病视网膜病变模型用于临床和科研.     

The role of optic nerve blood flow in the pathogenesis of glaucoma

Many theories have surfaced regarding the exact mechanisms behind glaucomatous damage, but the complex nature of the disease and the inaccessibility of the internal structures of the human eye have limited current knowledge. Increased intraocular pressure is the risk factor most often associated with glaucomatous optic neuropathy; ischemic insult to the optic nerve has also been suggested as a possible cause of cellular damage. The aim of this review is to cover the possible role of optic nerve head hemodynamics in the pathogenesis of glaucoma.     

糖尿病视网膜病变患者视网膜组织学改变和细胞生化检测指标异常分析

目的评价糖尿病患者视网膜组织学改变和细胞生化检测指标异常。方法将视网膜分为4个象限,胰酶消化法分离视网膜血管,比较各象限病变程度,将颞侧和鼻侧视网膜匀浆后检测其细胞生化指标。结果视网膜微动脉瘤、无细胞血管及凋亡周细胞的数量以颞侧多于鼻侧。视网膜各象限的糖转移因子、蛋白激酶C-β、半胱氨酸蛋白酶-1的检测结果明显不同。结论视网膜微血管病变和细胞生化检测指标异常程度在糖尿病视网膜病变患者视网膜的4个象限分布不均,推测其分布差异在糖尿病视网膜病变的发生、发展中起重要作用。（中华眼科杂志,2004,40：689-691)     

Cytokines and their role in pathogenesis of diabetic retinopathy

The role of cytokines is estimated in development of diabetic retinopathy. Titer of cytokines is compared in healthy subjects and patients with impaired glucose metabolism. Fundus examination and specific cytokines level assessment allowed us to conclude that cytokines directly take part in pathogenesis of retinopathy before clinical manifestation. It provides rational to use cytokine level as a predictor of early manifestation of diabetic retinopathy, its timely treatment and prevention of progressing till end stages.     

Preretinopathic changes in the oscillatory potential in diabetic retina: interpretation and significance

1) The earliest electroretinographic manifestation of diabetic retina is a selective change in the oscillatory potential (OP), which originates in postsynaptic retinal neuronal circuits. "Diabetic intraretinal neuropathy" precedes angiopathic retinopathy. 2) The peak latency and the amplitude of the OP are significantly correlated with the psychophysical contrast threshold for motion perception (CTMP) measured with our original device. 3) The CTMP is not correlated with the conventional static contrast threshold measured with a commercially available chart (VCTS-6000). 4) The CTMP is beyond the upper limit in nondiabetic control eyes in 135 out of 162 diabetic eyes at stage 0 (no ophthalmoscopic diabetic retinopathy) and all retinopathic eyes at stages AI (11 eyes) and AII (21 eyes). The CTMP test, which is completely non-invasive and easy to perform, could be useful for mass-screening of early diabetic retinal dysfuction. 5) The amplitude of the OP is enhanced by dopamine and nomifensine (a potent dopamine-uptake blocker), and diminished by haloperidol (a potent antagonist to dopamine D1-D2 receptors). Intrinsic dopamine release in the retina would regulate the amplitude of the OP. 6) The intraretinal content of dopamine decreases in streptozotocin (STZ)-induced diabetic rats where the OP amplitude is diminished, and increases in eyes where the OP amplitude is enhanced at the early stage in spontaneously diabetic (OLETF) rats. The changes in the OP amplitude in STZ-induced and OLETF diabetic rats can not be accounted for by the intraretinal content of gamma-aminobutyric acid (GABA), glycine, glutamate, aspartate or taurine. The changes in the OP amplitude in the diabetic retina are at least partly due to dysfunction of dopaminergic retinal neurons. 7) The peak latency prolongation and the amplitude diminution of the OP in STZ-induced diabetic rats are normalized after insulin treatment, while vitreous fluorescein concentration by vitreous fluorophotometry is not restored by insulin. Thus, the OP changes in STZ-induced diabetic rats are not due to STZ toxicity but to diabetes per se, and are not attributable to blood-ocular barrier disruption as revealed by vitreous fluorophotometry. Retinal neuronal dysfunction revealed by the OP changes at the early preretinopathic stage in STZ-induced diabetic rats is reversible after insulin treatment. 8) The OP changes in OLETF rats are prevented by decreasing food intake by 30% to maintain their blood glucose level and body weight normal. Even in highly genetically diabetic animals, diet therapy starting at an early stage of life inhibits the diabetic OP changes. 9) The amplitude of the bicarbonate response from the retinal pigment epithelium diminishes even at the preretinopathic stage, and is significanly correlated with the peak latency and the amplitude of the OP. Diabetic retinal pigment epitheliopathy as well as retinal neuropathy takes place prior to angiopathic retinopathy in the diabetic retina.     

The pathogenesis of diabetic retinopathy

Diabetic retinopathy remains a major cause of loss of vision. The Diabetes Control and Complications Trial (DCCT) has implicated hyperglycaemia as a probable major direct causative factor in the pathogenesis of diabetic retinopathy. There are several plausible mechanisms by which high glucose concentrations could lead to the functional and later structural changes characterising diabetic retinopathy. These include increased activity of the aldose reductase pathway, increase de novo synthesis of diacylglycerol from glucose, causing protein kinase C activation, increased non-enzymatic glycation and increased oxidative damage. The demonstration of the potential roles of these pathways and the subsequent effects of growth factors in enhancing angiogenesis provide potential new approaches to the prevention and treatment of diabetic retinopathy.     

Cirrhosis-induced morphological changes in the retina:possible role of endogenous opioid

AIM:To investigate the impact of cirrhosis on retinal morphology and to evaluate the role of endogenous opioids as a mediator in cirrhosis induced retinal change.METHODS:Thirty-six male rats were divided into 3 main groups; the common bile duct ligated (BDL) group, the sham-operated (Sham) group and the unoperated (Unop) group. Then each of these three main groups was divided into two subgroups; the first subgroup received daily injection of naltrexone hydrochloride (NTX) and the second group was injected with normal saline (Saline) daily. After 28d, rats were anesthetized and their right eyes were enucleated and assessed for histological changes. The thickness of the rod and cons layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer and ganglion cell layer for each eye were measured in micrometers by light microscope.RESULTS:Ganglion cell layer showed significant increase in thickness in the BDL group (P<0.05). This increase was eliminated in the group where BDL rats received daily intraperitoneal injection of naltrexone hydrochloride (20 mg/kg). No other histological changes were detected in the other 5 layers we measuredCONCLUSION:The morphological change we detected in the retina of cirrhotic rats is probably due to opioids increased tone in cirrhosis since the increase in thickness in the ganglion cell layer was almost eliminated when naltrexone hydrochloride was injected. These results suggest a possible role for endogenous opioids in the morphological retinal changes detected in cirrhotic rats.