B7：CD28／CTLA—4共刺激分子及其在眼科的研究进展

大量实验证实B7家族分子与其受体CD28和CTLA-4结合后所产生的共刺激信号在T淋巴细胞激活中起重要作用,决定着受到抗原刺激的T细胞是分化、增殖为效应细胞,还是进入无反应状态,其在眼科的研究主要集中于眼科自身免疫性疾病、角膜和视网膜三个方面,阻断B7：CD28/CTLA-4态。其在眼科的研究主要集中于眼科自身免疫性疾病、角膜和视网膜三个方面,阻断B7：CD28/CTLA-4通路可能为眼科自身免疫性疾病、角膜移植排斥反应和视网膜葡萄膜疾病的治疗提供新的途径,本就其分子特性、功能及其在眼科的研究进展等方面的有关资料作一综述。     

B7:CD28/CTLA-4共刺激分子及其在眼科的研究进展

大量实验证实B7家族分子与其受体CD2 8和CTLA 4结合后所产生的共刺激信号在T淋巴细胞激活中起重要作用 ,决定着受到抗原刺激的T细胞是分化、增殖为效应细胞 ,还是进入无反应状态。其在眼科的研究主要集中于眼科自身免疫性疾病、角膜和视网膜三个方面 ,阻断B7:CD2 8/CTLA 4通路可能为眼科自身免疫性疾病、角膜移植排斥反应和视网膜葡萄膜疾病的治疗提供新的途径。本文就其分子特性、功能及其在眼科的研究进展等方面的有关资料作一综述。     

眼眶炎性假瘤的诊疗进展

眼眶炎性假瘤是原发于眼眶的慢性非特异性炎性疾病，是常见的眼眶疾病。其诊断主要依靠影像学及病理学检查。治疗以糖皮质激素、放射治疗及手术治疗为主。近年采用生物制剂、强力霉素等新的尝试治疗眼眶炎性假瘤，在给药方法和剂量的选择上也有新的突破，如眼眶内注射小剂量曲安奈德等。（国际眼科纵览，2019, 43： 426-430）     

甲氨蝶呤在眼科的应用及安全性

甲氨蝶呤(Methotrexate,MTX)是一种叶酸类似物，具有抗增殖、抗炎和免疫调节作用。在临床上广泛用于治疗多种疾病，包括恶性肿瘤和自身免疫性疾病。MTX通过眼局部注射或者全身给药用于眼科疾病的治疗，其安全性和有效性均已被证实。其中玻璃体腔注射可以减少糖皮质激素及免疫抑制剂的全身使用，在眼科的应用越来越广泛。MTX在备孕期男性及女性、妊娠期妇女、哺乳期妇女、儿童、青少年及老年人等特殊患者人群中的应用有其特殊性，用药情况因患者而异。低剂量MTX常见不良反应包括胃肠道症状、肝功能异常等，比较少出现严重的不良反应，但仍应做好药学监护。该篇综述总结MTX的临床使用方法及其不良反应，为其在眼科的临床应用提供参考。     

糖皮质激素对小梁网的作用研究进展

应用糖皮质激素可引起眼压升高，它与原发性开角型青光眼关系密切。糖皮质激素对小梁网的作用可作为一个良好模型用于研究青光眼的发病机制。糖皮质激素对小梁网的作用是多方面的，它包括细胞外基质、细胞膜、细胞骨架及细胞核的多重变化。糖皮质激素受体的分子机制的新发现有助于从受体角度了解青光眼的发病机制。     

表皮生长因子在眼科疾病中的作用

表皮生长因子(epidermal growth factor,EGF)是一种多功能生长因子,通过与其受体(epidermal growth factor receptor,EGFR)结合,在体内外对多种组织细胞生长和增殖具有明显的调节作用.研究证实,EGF在角膜、视网膜和巩膜均有表达,在眼球主动生长和结构重塑过程中起重要作用.EGF还与角膜损伤、视网膜增生性疾病、近视、翼状胬肉、青光眼、白内障、眼科肿瘤等多种眼科疾病密切相关.本文就EGF在眼科疾病中的作用进行综述.     

核受体与眼科疾病

核受体是人体中含量最丰富的转录因子之一,通过与相应的配体及其辅助调节因子相互作用,调控基因的表达,从而在机体的生长发育、新陈代谢、细胞分化、细胞内环境的稳定及体内许多生理过程中发挥重要作用.很多疾病的发生和发展都与核受体有着直接或间接的联系,这也是核受体受到广泛关注的原因.近年来大量的研究发现核受体产生的作用贯穿于眼球的发育、角膜病、白内障、青光眼、年龄相关性黄斑变性、视网膜色素变性、视网膜新生血管病变、眼科肿瘤等眼科疾病的发生和发展.值得注意的是,某些难治性疾病,特别是糖尿病和某些癌症,如前列腺癌和乳腺癌中已有核受体相关靶点药物进入临床,其研究前景可见一斑.相信不断发现相关核受体与眼科疾病的关系能更好地理解疾病的发展过程,利于疾病的诊断与鉴别诊断,也能在治疗上带来新的启发,使靶向治疗成为现实,甚至让个体化用药成为可能.本文主要就核受体的基本背景及其与眼科疾病的关系进行综述.     

激素性白内障的发病机制研究

糖皮质激素在许多生理过程中发挥重要作用,并被广泛应用于临床,在器官移植、战伤和免疫性疾病等救治过程中使用剂量更大。流行病学资料已证实长期全身、局部应用及吸入糖皮质激素治疗均可引起以晶状体后囊混浊为特征的激素性白内障。激素性白内障的发病机制复杂。主要形成了氧化损伤学说、蛋白加和物学说、激素通过受体途径而发挥作用的受体学说、离子转运障碍学说、晶状体结构蛋白和酶功能损害学说、细胞黏附分子异常学说。激素不仅可能直接攻击晶状体蛋白质,而且也可能通过受体、细胞调控、黏附调节等间接发挥作用。最近研究已证实晶状体上皮细胞中存在糖皮质激素受体,这将有助于阐明激素性白内障发生机制,为药物预防和治疗白内障提供新思路。     

应用糖皮质激素导致颅眶占位性病变误诊

应用糖皮质激素导致颅眶占位性病变误诊北京天坛医院眼科金崇华糖皮质激素（简称激素）在眼科的广泛应用，使许多疾病的疗效颇为显著。但是应用激素后，有时会造成视功能暂时增进的假象，以致未能进一步检查而延误诊断。现将我院１９８８－１９９２年收治的经手术证实为颅...     

新型C型凝集素受体mincle的研究进展

巨噬细胞诱导型C型凝集素受体mincle是一种新发现的非经典型C型凝集素受体,主要表达于抗原递呈细胞表面,可以在某些真菌、结核分枝杆菌、坏死细胞的刺激下与相关配体结合,激活核因子-κB(NF-κB)途径,引起炎性因子的表达,从而在宿主的固有免疫应答过程中发挥一定的作用.目前,mincle受体在一些免疫相关疾病中作用机制的研究成为热点,但关于其在眼科炎性感染性疾病中作用的研究甚少,深入研究mincle受体与眼科感染性疾病的关系可以为相关疾病的免疫治疗提供新的思路.就mincle受体的基本概念、作用机制、与炎性疾病的关系以及其在眼科疾病研究中的展望进行综述.     

糖皮质激素在眼眶病中的应用及研究进展

糖皮质激素是类固醇激素的一种,具有强大的抗炎和免疫调节的作用,已广泛应用于临床多种炎症和免疫性疾病的治疗中。糖皮质激素在眼眶病中的应用主要体现在眼眶炎症和免疫相关性疾病如甲状腺相关眼病、特发性眼眶炎性假瘤和泪腺良性淋巴上皮病变等的治疗上。对糖皮质激素在眼眶病的应用及研究进展进行综述。     

Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy

Loss of blood-retinal barrier (BRB) integrity and vascular permeability characterizes diabetic retinopathy, and new therapies to reverse or prevent vascular permeability are needed to treat this debilitating disease. Glucocorticoids are currently under investigation for use as a local therapeutic treatment for diabetic retinopathy. This review examines the changes that occur to barrier properties in diabetic retinopathy and the potential to use glucocorticoids to restore vascular barrier properties in the retina. Glucocorticoids are useful in preserving the integrity of the blood-brain barrier in the treatment of brain tumors, and these steroids show similar effects on the retinal vasculature suggesting their potential usefulness in treating diabetic retinopathy. Recent progress has been made toward the goal of elucidating the precise mechanism underlying the protective effects of glucocorticoids on the retinal vasculature. Glucocorticoids may act by both suppressing inflammation and by directly affecting the endothelial cells by regulating phosphorylation, organization, and content of tight junction proteins. Further work will advance our understanding of glucocorticoid regulation of barrier properties allowing the ultimate goal of developing a specific and safe therapy to treat or prevent loss of the blood-neural barrier in a number of diseases, including brain tumors and diabetic retinopathy.     

Characterisation of reticular pseudodrusen and their central target aspect in multi-spectral,confocal scanning laser ophthalmoscopy

Background

To analyse reticular pseudodrusen (RPD) in patients with age-related macular degeneration (AMD) using multi-spectral (MS), confocal scanning laser ophthalmoscopy (cSLO).

Methods

cSLO images (blue fundus autofluorescence [FAF; exc., λ?=?488; em., λ?=?500–700 nm], near-infrared reflectance [IR; λ?=?820 nm], MS [blue reflectance (BR) λ?=?488 nm, green reflectance (GR) λ?=?515 nm, IR λ?=?820 nm], as well as colour fundus photographs (CFP) were taken of 200 eyes from 100 AMD patients suspected to show RPD on the basis of funduscopy or previous fundus imaging. FAF and IR images were graded by two independent readers. If both readers concordantly confirmed the presence of RPD in both modalities, eyes were subsequently also graded for RPD in MS, BR, GR, green-blue enhanced mode (GBE), and CFP. Besides, FAF, IR, and MS images were evaluated for the presence of a target aspect, which represents a common feature of RPD lesions.

Results

The presence of RPD was confirmed using FAF and IR images by both readers in 130 eyes of 76 patients. In those eyes, both readers concordantly diagnosed RPD in MS images in 124 (95.4 %) eyes (BR: 52 [40.0 %], GR: 63 [48.5 %], GBE: 101 [77.7 %], CF: 27 [20.8 %]). Cohen kappa statistics revealed excellent inter-observer agreement for MS (0.95) and GBE (0.85), substantial agreement for BR (0.75), GR (0.78), and moderate agreement for CFP (0.59). A target aspect within RPD lesions was detected in 45 of 130 (35.0 %) included eyes using FAF and IR. The presence of a target aspect improved the recognition of RPD lesions in all modalities. If a target aspect was present, RPD were diagnosed in 45 eyes (100 %) using MS (GBE: 42 eyes [93.3 %], BR: 30 eyes [66.7 %], GR: 37 eyes [82.2 %], CFP: 17 eyes [37.8 %]). Using MS cSLO, a target aspect could be identified in 75 of 130 (57.7 %) included eyes.

Conclusions

MS cSLO imaging is equivalent to FAF and IR in identifying RPD in AMD patients. Higher identification rates in BR and GR of those RPD lesions featuring a target aspect confirm the current hypothesis of RPD localisation and its progression further into the photoreceptor layers. MS seems to be more sensitive in identifying a central target aspect in RPD lesions compared to blue FAF and IR.     

兔外周血淋巴细胞和小梁组织中糖皮质激素受体与激素性青光眼关系的研究

目的检测兔外周血淋巴细胞和小梁组织中糖皮质激素受体(GR)含量并探讨其与激素性青光眼的关系。方法隔日给兔眼球结膜下注射地塞米松1个月,制作糖皮质激素性高眼压模型。实验前后采用3H地塞米松放射配体法,测定兔外周血淋巴细胞与小梁细胞GR数目,探讨其两者间的关系,比较初始GR含量和GR表达的变化与高眼压的关系。结果兔外周血淋巴细胞和小梁细胞均表达GR,淋巴细胞GR表达水平为(3642±947)位点/细胞,小梁细胞GR含量为(2437.85±733.93)dmp/mg,两者表达水平呈正相关(r=0.862,P<0.01)。3H地塞米松处理组,兔外周血淋巴细胞中GR受体数量下降,眼压升高。实验前与实验后兔外周血淋巴细胞中GR数量变化与眼压升高的程度呈正相关(r=0.78,0.79;P<0.01)。结论外周血淋巴细胞中GR数量可间接反映小梁细胞的GR水平,与糖皮质激素性青光眼的发病密切相关。     

Revival of glutathione reductase in human cataractous and clear lens extracts by thioredoxin and thioredoxin reductase, in conjunction with alpha-crystallin or thioltransferase

Glutathione reductase (GR) plays a key role in maintaining thiol groups in the lens, and its activity decreases with aging and cataract formation. Mammalian thioredoxin (Trx) and thioredoxin reductase (TrxR), or the Trx/TrxR system, participates in the repair of oxidatively damaged lens proteins and enzymes. Alpha-crystallin, a molecular chaperone, prevents the aggregation of partially denatured proteins under various stress conditions. Thioltransferase (TTase, or glutaredoxin) can maintain the homeostasis of lens protein thiols thus protecting against oxidative stress. We investigated whether the Trx/TrxR system can revive GR activity in both the cortex and nucleus of human cataract and clear aged lenses and whether alpha-crystallin and TTase can help this effect. The GR activity in the cortex and nucleus of the cataractous lenses was significantly lower than that of the aged clear lenses. The highest activity in the cortex was observed in the clear aged lenses. The combination of Trx and TrxR revived the activity of GR from both the cortex and nucleus of aged clear lenses. However, in cataract lenses (grade II and grade IV), there was a statistically significant recovery of GR activity in the cortex, but not in the nucleus. No recovery was observed when Trx or TrxR were used separately. Alpha-crystallin successfully revived GR activity in the cortex of cataract grade II lenses, but not in the nucleus. The combination of alpha-crystallin and Trx/TrxR gave a further increase of activity. TTase alone revived some of the GR activity but together with the Trx/TrxR system gave no statistically significant enhancement of GR activity. These results indicate that both disulfide bond formation and protein unfolding are responsible for GR inactivation.     

Studies on the mechanism of the UVA light-dependent loss of glutathione reductase activity in human lenses

PURPOSE: To determine the mechanism that leads to the UVA light-dependent loss of glutathione reductase (GR) activity in human lens (HL). METHODS: Both the HL water-soluble (WS) fraction and yeast GR were irradiated with UVA light (200 mW/(cm(2). h) for 1 hour at +20 degrees C, and the specific activity (SA) was observed. GR apoenzyme (apo-GR) was prepared from either HL-WS fractions or yeast GR by treatment with a cold solution of acidic ammonium sulfate. Reconstitution of apo-GR was conducted by mixing enzyme with an excess of flavine adenine dinucleotide (FAD) and purification of GR on a size-exclusion separation column. RESULTS: One hour of UVA photolysis of an HL-WS fraction resulted in a 96% decrease in the SA of GR (6.32 +/- 0.22 vs. 0.39 +/- 0.01 mU/mg lens protein). Action spectra of GR SA in the WS fraction from HL within the range 320 to 500 nm showed that the enzyme was most vulnerable to the wavelengths in the UVA region with the highest decrease in the SA at 320 to 350 nm ( approximately 23%-28% activity loss within 1 hour of irradiation), and lowest with the wavelengths beyond 400 nm (7%-8% SA loss). UVA irradiation of apo-GR in the crude HL-WS fraction, followed by reconstitution with FAD, showed that 90% of the original SA was recovered. The original GR activity either in HL or yeast GR, however, was not recovered by (NH(4))(2)SO(4) (pH 2.25) treatment followed by reconstitution with FAD after UVA photolysis. Experiments with UVA-photolyzed yeast GR revealed that UVA photolysis caused the formation of additional SH groups within the enzyme, as shown by the incorporation of an SH-specific fluorescent probe, 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F). Similar results were obtained on the photolyzed iodoacetamide-alkylated yeast GR, which was evaluated by matrix-assisted desorption ionization-time of flight (MALDI-TOF) mass spectrometry. CONCLUSIONS: The results show that the reduction of HL GR activity by UVA light was directly linked to the presence of FAD within the enzyme. That the irradiated GR showed de novo formed SH groups argues that UVA photolysis of GR leads to the reduction of the redox-active disulfide within the reaction center of the enzyme, making it inactive.     

Studies of lens enzyme activities in relation to cataract type and plasma constituents

The specific activities of glutathione reductase (GR), EC 1.6.4.2, and aldolase, (ALD) EC 4.1.2.13, were determined in the homogenates of 60 cataractous lenses. Concentrations of certain plasma constituents and the morphological types of cataract of the patients were known. Investigations were aimed at establishing a possible correlation between enzyme activities and plasma constituents as well as between the specific activities of GR and ALD and type of cataract. A correlation between the specific activity of GR and the urea content of the blood could be identified. Results also indicated a relationship between the decrease in GR activity and the formation of cortical cataracts.