High vitreous concentration of vascular endothelial growth factor in diabetic patients with proliferative retinopathy using statins

Background. Vascular endothelial growth factor (VEGF) plays an important role in the development of diabetic retinopathy. Previous studies have suggested that angiotensin‐converting enzyme (ACE) inhibitor therapy may reduce vitreous VEGF concentration in diabetic retinopathy. Also HMG CoA reductase inhibitors (statins), known for their beneficial effects on vascular endothelium, might influence vitreous VEGF concentration in diabetic retinopathy.

Aim. Vitreous VEGF concentration of diabetic patients with proliferative retinopathy using statin therapy and/or ACE inhibitor therapy was studied.

Methods. Fifty diabetic patients with proliferative diabetic retinopathy, 21 diabetic control patients without proliferative retinopathy, and 43 non‐diabetic control subjects underwent vitrectomy. Vitreous samples were collected at the beginning of surgery, and VEGF concentration was assessed using a chemiluminescent VEGF immunoassay.

Results. Vitreous VEGF concentration was significantly higher in diabetic patients with proliferative retinopathy using statins than in those not using statins. The diabetic patients with proliferative retinopathy were divided into subgroups according to use of ACE inhibitor and/or statin medication. These groups did not differ significantly in concentration of vitreous VEGF.

Conclusions. Statin therapy is associated with high vitreous VEGF concentration in diabetic patients with proliferative retinopathy. In contrast to previous reports, ACE inhibitor use did not significantly influence vitreous VEGF concentration in these patients.     

Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n =21) and non-diabetic patients (n =13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16 ng/ml; range 0.06-0.57 ng/ml) in comparison with group B (median, 0.12 ng/ml; range 0.06-0.22 ng/ml; P <0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05 ng/mg (0.01-0.45 ng/mg) versus 0.15 ng/mg (0.07-0.66 ng/mg); P <0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.     

增殖型糖尿病视网膜病变患者行玻璃体切除联合术的护理

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病的严重并发症之一,严重影响患者视力,治疗不及时可导致失明 [1] ,DR早期可以采用激光治疗,晚期发展至增殖型糖尿病视网膜病变(proliferative diahetic retinopatlhy,PDR)时,由于玻璃体积血,纤维增殖膜形成等因素的影响,使眼外激光往往不能成功实施,这时只能通过玻璃体切除来治疗本病 [2] ,手术中不仅术者具有娴熟的手术技巧,同时要求护士默契的同步配合很重要.我科2005年1月-2008年10月实行此手术334例,收到良好效果,现报道如下.     

增殖性糖尿病视网膜病变玻璃体切割术病人的护理

[目的]探讨增殖性糖尿病视网膜病变(PDR)的术后观察与护理方法.[方法]对2003年-2004年在我院行玻璃体切割手术治疗PDR中、晚期病人78例83眼,进行视网膜解剖复位、术后疼痛、术后视力提高标准的分析.[结果]66眼(79.5%)视网膜解剖复位;10眼(12.0%)大部分复位;4眼(4.8%)未复位;2眼(2.4%)因视网膜呈闭斗状分离时术中出血难以控制,术后呈血性硅油状态;1例(1.2%)剥膜时出现多处医源性裂孔,网膜增殖僵硬粘连难于复位.术后视力提高情况:68眼视力增进,13眼无变化、2眼视力下降.术后疼痛情况:轻度疼痛18例,中度32例,重度9例.[结论]玻璃体切割手术治疗PDR手术难度大,护理要求高,恢复时间长,且此类病人大多体质虚弱,视力低下,对生活的依赖性高,因此,有针对性的高质量、高素质的护理,对增殖性糖尿病性视网膜病变病人的早日康复尤其重要.     

增殖性糖尿病视网膜病变玻璃体切割术病人的护理

[目的] 探讨增殖性糖尿病视网膜病变（PDR）的术后观察与护理方法。[方法] 对2003年-2004年在我院行玻璃体切割手术治疗PDR中、晚期病人78例83眼，进行视网膜解剖复位、术后疼痛、术后视力提高标准的分析。[结果] 66眼（79．5％）视网膜解剖复位；10眼（12．0％）大部分复位；4眼（4．8％）未复位；2眼（2．4％）因视网膜呈闭斗状分离时术中出血难以控制．术后呈血性硅油状态；1例（1．2％）剥膜时出现多处医源性裂孔，网膜增殖僵硬粘连难于复位。术后视力提高情况：68眼视力增进．13眼无变化、2眼视力下降。术后疼痛情况：轻度疼痛18例，中度32例，重度9例。[结论] 玻璃体切割手术治疗PDR手术难度大，护理要求高，恢复时间长，且此类病人大多体质虚弱，视力低下，对生活的依赖性高，因此，有针对性的高质量、高素质的护理，对增殖性糖尿病性视网膜病变病人的早日康复尤其重要。     

结缔组织生长因子在糖尿病大鼠肾脏中的表达

目的 通过观察结缔组织生长因子（CTGF）在糖尿病大鼠肾脏中表达的动态改变,探讨CTGF在糖尿病肾病发生发展中的作用。方法 尾静脉内注射链脲佐菌素（STZ）诱导糖尿病大鼠模型。采用RT-PCR和Western blot检测1个月、3个月和6个月时糖尿病大鼠肾脏组织中CTGF的mRNA和蛋白的表达。光镜下观察糖尿病大鼠不同时期肾脏组织形态学的改变。结果 糖尿病大鼠1个月、3个月和6个月与同期对照大鼠相比,肾脏CTGF的mRNA表达上调,分别为对照组的1.56倍、2.05倍和3.74倍（P〈0.01）;同时蛋白表达亦上调,分别为对照组的2.48倍、2.93倍和5.82倍（P〈0.01）;此外,糖尿病6个月大鼠的CTGF mRNA和蛋白的表达明显高于糖尿病1个月和3个月大鼠的表达水平（P〈0.01）。组织形态学观察表明,糖尿病大鼠3个月时肾脏出现基膜增厚、肾小球扩张等糖尿病肾病早期的病理改变,随着病程的延长,病理改变越严重;6个月时出现肾小球硬化、肾间质纤维化等晚期的改变。结论 糖尿病大鼠早期肾脏已存在CTGF基因表达上调,在糖尿病肾病的发展过程中,CTGF基因表达上调仍持续存在。因此,CTGF基因表达上调在糖尿病肾病的发生发展中起着重要作用。     

玻璃体中胰岛素样生长因子水平与增殖性糖尿病性视网膜致盲性眼病发生发展的相关性研究

目的:观察人胰岛素样生长因子1,2(insulin-likegrowthfactor-1,2,IGF-1,2)以及白蛋白在玻璃体中浓度,探讨眼球内IGF水平与增殖性糖尿病性视网膜病变(proliferativediabeticretinopathy,PDR)的相关性。方法:1999-04/2001-12哈尔滨医科大学第一临床医学院眼科收治患者66例,对照组33例无PDR,观察组33例患有PDR,IGF-1,2以及白蛋白的水平通过放射免疫方法测定。结果:PDR患者玻璃体中白蛋白水平为正常对照组升高2.23倍。PDR患者IGF-1为(2.4±1.2)μg/L(P=0.0005);IGF-2为(38.6±5.1)μg/L(P=0.0004,n=33);对照组犤IGF-1:(0.8±0.2)μg/L,IGF-2:(21.5±4.3)μg/L(n=33)犦。结论:PDR患者玻璃体内IGF水平升高,是PDR发病机制的重要因素。通过应用抑制和降低IGF水平的干预方法,早期防治PDR及其致盲性眼病的发生。     

体力活动对增生性糖尿病视网膜病变患者玻璃体积血的安全性分析

目的 通过对比发生玻璃体积血与无明显玻璃体积血增生性糖尿病视网膜病变（PDR）患者不同体力活动形式及强度的差异,探讨体力活动对PDR患者的安全性及潜在价值。方法 首次在开封市中心医院开封眼病医院就诊的无明显纤维组织增生的PDR患者67例,其中31例无明显玻璃体积血PDR患者为对照组,36例发生玻璃体积血（<1月）患者为研究组。采用国际体力活动量表（IPAQ）统计患者玻璃体积血发生前的体力活动。同时记录患者年龄、病程、最佳矫正视力（BCVA）、身高、体重指数（BMI）、糖化血红蛋白、血脂、血压。 调查出血诱因,比较两组间体力活动的差异。结果 36例发生玻璃体积血患者中未见体力活动直接诱发玻璃体积血病例;研究组大量患者部分体力活动缺失,中、重体力活动、总体力活动、能量消耗、休闲及运动相关体力活动时间及人数显著低于对照组(P＜0.05);研究组静坐时间显著延长,睡眠时间显著缩短,BMI、甘油三酯、收缩压显著高于对照组(P＜0.05)。结论 不同体力活动未见诱发玻璃体积血;不同体力活动对无明显纤维组织增生PDR患者可能是安全和有益的;减少静坐时间、改善睡眠质量值得提倡。     

Changes in vitreous concentrations of human hepatocyte growth factor (hHGF) in proliferative diabetic retinopathy: implications for intraocular hHGF production

We measured human hepatocyte growth factor (hHGF) concentrations in the original vitreous and in the artificial vitreous after vitrectomy in 13 patients with proliferative diabetic retinopathy (PDR) undergoing repeated pars plana vitrectomy, in order to investigate whether the vitreous hHGF concentration is related to the recurrence of PDR after vitrectomy as well as to the original occurrence of PDR. We also examined the relationship between vitreous concentrations of hHGF and transforming growth factor-beta(2) (TGF-beta(2)), the predominant TGF-beta isoform in the vitreous, in 14 patients with PDR. For the original vitreous, mean hHGF concentrations were higher (P<0.05) in that from patients with severe PDR (vitreous haemorrhage, fibrovascular proliferation and tractional retinal detachment) than in that from patients with vitreous haemorrhage alone. In the artificial vitreous, mean vitreous hHGF concentrations were higher (P<0.05) in that from patients with severe PDR than in that from patients with vitreous haemorrhage alone or with vitreous haemorrhage plus fibrovascular proliferation. No correlation was found between the hHGF concentration in the artificial vitreous and time between vitrectomies. Vitreous hHGF concentrations were directly proportional to vitreous concentrations of latent TGF-beta(2) (r=0. 831; P=0.0002), but inversely proportional to vitreous concentrations of active TGF-beta(2) (r=0.495; P=0.072), which inhibits hHGF production. A decreased conversion of latent into active TGF-beta(2) in ocular disorders such as PDR is likely to result in an increased concentration of hHGF in the vitreous. Thus intraocular hHGF may be involved in pathological mechanisms causing not only the occurrence, but also the recurrence, of PDR.     

Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy

OBJECTIVE: To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS: A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry. RESULTS: SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 +/- 18.7 vs. 193.6 +/- 30.8 pg/ml, P < 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2-71.1] vs. 0.6 [0.03-4.1], P < 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with PDR (186 [51-463] vs. 7.5 [0.8-82], P < 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 +/- 30.8 vs. 43.5 +/- 10.7 pg/ml, P < 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects. CONCLUSIONS: The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization.     

糖尿病大鼠皮肤伤口愈合过程中结缔组织生长因子的表达

背景:结缔组织生长因子表达在糖尿病伤口愈合过程中的变化及意义少见报道.目的:观察链脲佐菌素诱导的糖尿病模型大鼠复合创伤修复过程中结缔组织生长因子表达的变化及意义.方法:将Wistar大鼠随机分成正常对照组和模型组,3周后将各组动物复合背部1.3 cm2全厚皮切除形成伤口.结果与结论:链脲佐菌素诱发的糖尿病模型大鼠伤口愈合明显延迟,创伤后第4,8,12 和16天创面愈合率明显低于正常对照组(P < 0.01).术后第8天,糖尿病组大鼠肉芽组织成熟度和新生血管形成指标得分均低于正常对照组(P < 0.01).正常对照组的结缔组织生长因子蛋白表达呈时间递增趋势,而糖尿病组的结缔组织生长因子表达在整个创面愈合过程的后期(第12天后)均明显低于正常对照组(P < 0.01).结果提示,糖尿病大鼠皮肤伤口愈合后期创面组织结缔组织生长因子表达相对正常对照组减少可能是导致创面愈合迟缓的重要原因之一.     

糖尿病大鼠皮肤伤口愈合过程中结缔组织生长因子的表达

背景：结缔组织生长因子表达在糖尿病伤口愈合过程中的变化及意义少见报道。目的：观察链脲佐菌素诱导的糖尿病模型大鼠复合创伤修复过程中结缔组织生长因子表达的变化及意义。方法：将Wistar大鼠随机分成正常对照组和模型组,3周后将各组动物复合背部1.3cm2全厚皮切除形成伤口。结果与结论：链脲佐菌素诱发的糖尿病模型大鼠伤口愈合明显延迟,创伤后第4,8,12和16天创面愈合率明显低于正常对照组（P〈0.01）。术后第8天,糖尿病组大鼠肉芽组织成熟度和新生血管形成指标得分均低于正常对照组（P〈0.01）。正常对照组的结缔组织生长因子蛋白表达呈时间递增趋势,而糖尿病组的结缔组织生长因子表达在整个创面愈合过程的后期（第12天后）均明显低于正常对照组（P〈0.01）。结果提示,糖尿病大鼠皮肤伤口愈合后期创面组织结缔组织生长因子表达相对正常对照组减少可能是导致创面愈合迟缓的重要原因之一。     

Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects

OBJECTIVE: There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS: Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14. RESULTS: The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102-837] vs. 78 [24-32] pg/ml; patients with PDR: 187 [87-998] vs. 62 [24-472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 +/- 32 vs. 595 +/- 66 pg/ml; P = 0.004). CONCLUSIONS: Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment.     

微小RNA-126和血管内皮生长因子在增殖性糖尿病视网膜病变患者视网膜前膜中的表达及意义

目的 探讨微小RNA-126(miR-126)和血管内皮生长因子(VEGF)在增殖性糖尿病视网膜病变(PDR)患者视网膜前膜组织中的表达及临床意义.方法 选取眼科择期行玻璃体切割手术的PDR患者65例纳入研究组,另选取同期行玻璃体切割手术的特发性黄斑裂孔患者62例纳入对照组.采用实时荧光定量聚合酶链反应(qRT-PCR...