Choroidal mast cell dynamics during experimental autoimmune uveoretinitis in rat strains of differing susceptibility

Choroidal mast cells have been implicated in the pathogenesis of experimental autoimmune uveoretinitis (EAU). The aim of the present study was to examine the dynamics of choroidal mast cells during the course of EAU in rat strains of varying susceptibility. Histochemical staining showed choroidal mast cell degranulation in Lewis rats, a highly susceptible strain, commenced nine days post-immunisation, and peaked at day 11, at which time the percentage of degranulated choroidal mast cells (32. 5± 4%) was significantly higher than controls (15. 3 ± 3%; p <0.05). At day 14, mean choroidal mast cell density was significantly reduced (from 23. 6 ± 1/mm(2) tot 16. 2 ± 2/mm(2); p<0.05) and early signs of choroidal mast cell regeneration were evident. Immunisation of PVG/C (moderate susceptibility) and Brown Norway (very low susceptibility) rats produced a similar pattern of morphological changes. Onset of clinical signs in Lewis rats, which possess approximately 1100 to 1800 choroidal mast cells per eye, occurred one day following commencement of choroidal mast cell degranulation but prior to the peak of degranulation. However, in PVG/C and Brown Norway rats, which possess only approximately 70 and 110 choroidal mast cells per eye respectively, onset of disease was not temporally linked to commencement of degranulation. Production of antigen-specific IgE during the course of EAU was extremely low in all three strains. These results indicate that choroidal mast cells may be important in the pathogenesis of EAU in Lewis rats but not in PVG/C or Brown Norway rats and that non-IgE mediated degranulation may play a role in disease induction.     

Induction of experimental autoimmune uveoretinitis and pinealitis by IRBP. Comparison to uveoretinitis induced by S-antigen and opsin

Microgram quantities bovine IRBP (interphotoreceptor retinoid binding protein) injected in Freund's complete adjuvant induced severe autoimmune uveoretinitis and pinealitis in Lewis rats. At low doses the onset was accelerated and intensified by co-injection of Hemophilus pertussis bacteria. Wistar, BN and PVG rats were less susceptible, while the eyes of athymic, nude rats did not respond. The disease developed similar to but faster than S-antigen-induced uveoretinitis, while its onset was one day earlier and the reactions were slightly more severe. As distinct from these two types of uveoretinitis, opsin (in much higher doses) caused milder reactions in the anterior segment, while retinitis dominated. In each type of inflammation the photoreceptor cell layer was totally destroyed. All three ocular diseases were inhibited by cyclosporine treatment, which indicates that T cell-dependent mechanisms are essential for the development.     

Comparison between histopathologic findings and indocyanine green angiographic findings in Lewis rats with experimental autoimmune uveoretinitis

PURPOSE: Recently, indocyanine green angiography (IA) was used to examine chorioretinal circulation in posterior uveitis in humans, and abnormal IA findings were reported. However, choroidal pathologic examination in conjunction with these abnormal IA findings has rarely been done. Experimental autoimmune uveoretinitis (EAU) is a model for posterior uveitis in humans. The purpose of this study was to correlate abnormal IA findings in Lewis rats with EAU with pathologic findings. METHODS: Eleven male Lewis rats were immunized with bovine S-antigen in complete Freund's adjuvant with Bordetella pertussis. After immunization, IA was performed by using a scanning laser ophthalmoscope. Eyes with abnormal IA findings were enucleated and examined histopathologically. RESULTS: Demonstrated leakage from retinal vessels at the initial stage of disease; a decrease of background fluorescence and of the number of moderate and large vessels of the choroid, and leakage from choroidal vessels at the progressive stage; and hypofluorescent areas at the late stage. Histopathologic examination at the initial, progressive, and late stages revealed inflammation of the inner layers of the retina, a large number of inflammatory cells in the thickened retina and choroid, and impaired choroidal capillaries, respectively. CONCLUSION: Since a correlation between pathologic findings and IA findings was demonstrated in Lewis rats with EAU, IA may be useful for evaluating the severity of uveitis in humans.     

Mass cells in ocular tissues of normal rats and rats infected with Nippostrongylus brasiliensis.

In orbital exenteration specimens from 14 rats, 93% of the mast cells were found in the lids, the limbus, and the conjunctiva, 5% in the orbital tissues, and less than 1% in the globe. The density of mast cells was highest in lid (2843/mm3), limbus (2822/mm3), and orbit (2184/mm3) and lowest in bulbar conjunctiva (794/mm3), ciliary body (512/mm3), and sclera (176/mm3). There was no significant difference in the distribution or density of mast cells in orbital exenteration specimens from normal rats compared with rats infected with the worm Nippostrongylus brasiliensis. We concluded that certain ocular structures are rich in mast cells, which suggests that these structures might be susceptible to injury mediated by mast cell products.     

Macrophages and MHC class II positive cells in the choroid during endotoxin induced uveitis

AIMS/BACKGROUND—Endotoxin induced uveitis has been regarded as a model for acute anterior uveitis and until now little was known about choroidal involvement. The aim of this study was to investigate changes in macrophages and MHC class II positive cells in the choroid of Lewis rats during endotoxin induced uveitis.METHODS—Choroid-sclera wholemounts were isolated from normal Lewis rats and at different time points—4, 8, 16, 24, 48, 72, and 96 hours, and 7, 10, and 14 days after a footpad injection of 200 µg of lipopolysaccharide (LPS). Immunohistochemistry was performed using the monoclonal antibodies ED1 (monocytes, macrophages, dendritic cells), and OX6 (MHC class II antigen).RESULTS—In normal rats, two layers of macrophages were identified in the choroid; a layer located immediately beneath the retinal pigment epithelium (RPE) and a layer bordering the sclera. The density of ED1 positive cells in the layer bordering the RPE cells was 902 (SD 132) cells/mm² whereas the scleral layer had a cell density of 389 (73) cells/mm². Based on morphology, positive cells could be divided into two main categories; pleomorphic/round cells and dendritiform cells with varying appearances, with the latter being predominant in normal eyes. A network of MHC class II positive dendritic cells was found in the choroid, beneath the RPE, with a density of 659 (96) cells/mm². No MHC class II positive cells were found in the macrophage layer bordering the sclera. LPS injection caused a massive influx of ED1 positive macrophages in the area below the RPE cells but did not result in an influx of macrophages at the scleral side of the choroid. The infiltrate reached a maximum at 16 hours following LPS injection and decreased at 96 hours. The morphology of the infiltrating cells was pleomorphic/round at early stages of inflammation and changed into a dendritiform cell population later. The number of MHC class II positive cells on the anterior side of the choroid increased 8 hours after injection and reached a peak at 72-96 hours. MHC class II positive cells were not observed in the vicinity of the sclera at any time after LPS injection. Both resident and MHC class II positive dendritic cell numbers returned to normal values at day 14 following LPS injection.CONCLUSIONS—These results indicate that the choroid is severely inflamed after systemic LPS administration to Lewis rats and suggests that endotoxin induced uveitis may serve as a model for generalised uveitis in humans.     

Abstracts of the 187th Meeting of the Netherlands Ophthalmological Society (NOG) Utrecht,The Netherlands,March 17–19,1993

Injection of an antigen into the anterior chamber induces an immune response in which antibody production is normal while delayed hypersensitivity reactivity is depressed. Several antigens have been used to induce this response which has been termed anterior chamber associated immune deviation. We have demonstrated that allogeneic lymphocytes injected into the anterior chamber of Lewis rats increase the success rate of subsequent corneal grafts derived from the lymphocyte donor strain. To begin understanding the antigenic requirements of this phenomenon, Wistar/Furth lymphocytes were partially purified into B- and T-cell populations by panning on anti-immunoglobulin coated petri-dishes. These enriched populations were injected separately into the anterior chamber of Lewis rats. Two weeks later these Lewis rats received a full-thickness corneal graft derived from Wistar/Furth donors. Grafts were scored for opacity and neovascularization over the subsequent 8–10 weeks. In control animals injected with balanced salt solution, 20% of the grafts cleared sufficiently to be judged successful. Grafts placed on rats injected with unseparated splenic lymphocytes were judged successful in 75% of the cases. Comparable percentages for grafts on animals injected with B-cell enriched and T-cell enriched populations were 85 and 50 respectively. These results suggest that B cells, which express both class I and class II major histocompatibility antigens are more efficient at inducing anterior chamber associated immune deviation than are T cells, the majority of which express only class I major histocompatibility antigens.Abbreviations AC anterior chamber - ACAID anterior chamber associated immune deviation - W/F Wistar/Furth - MHC major histocompatibility - CPM CPM of experimental — CPM of control - SI stimulation index - IC intracamerally - BSS balanced salt solution - TNP trinitrophenol     

Morphometrische Veränderungen der Choriokapillaris sowie der Chorioidea in Augen mit fortgeschrittener glaukomatöser Schädigung

BACKGROUND: In addition to elevated intraocular pressure, a compromised ocular blood supply has been implicated in the pathogenesis of primary open-angle glaucoma (PCOG). METHODS AND MATERIALS: We analyzed 20 eyebank eyes with end-stage PCOG and compared these with 20 age-matched controls. The following variables were measured: density and diameter of large choroidal vessels in the macular and equatorial choroid; thickness of the choroid in the macular and equatorial region; and density and thickness of choriocapillaris in the macular, peripapillary, and equatorial choroid. RESULTS: Eyes with glaucoma displayed a lower density of the capillaries of the choriocapillaris than control eyes in the macular, temporal peripapillary, and equatorial choroid, with 0.50 vs. 0.55 (P = 0.018), 0.46 vs. 0.51 (P = 0.016), and 0.50 vs. 0.55 (P = 0.038), respectively. Assessment of large choroidal vessels in the macular choroid showed that eyes with glaucoma had less density of veins (11.7 vs. 38.9/mm2; P < 0.001) and arteries (7.7 vs. 12.4/mm2; P = 0.005) and arteries with a higher diameter (45.6 vs. 28.2 microns; P < 0.001) than control eyes. The large vessels in the equatorial choroid displayed no significant difference in diameter but a lower density (21.2 vs. 44.1/mm2; P = 0.017) in eyes with glaucomatous damage than controls. CONCLUSION: Eyes with advanced glaucomatous damage after long-standing PCOG exhibit many changes in the choroidal vasculature. We cannot conclude from our study whether the observed vascular changes in the choroid are primary pathogenic factors or secondary phenomena.     

Ultrastructural Changes in Rat Eyes with Experimental Vogt-Koyanagi-Harada Disease

Purpose To determine whether the ultrastructural changes in the eyes of an animal model of Vogt-Koyanagi-Harada (VKH) disease are similar to those in human eyes with VKH disease.Methods Pigmented rats derived by crossing brown Norway and Lewis rats were immunized with tyrosinase-family proteins, and the eyes were enucleated after different postinoculation times. The eyes were fixed in glutaraldehyde or formaldehyde and prepared for light or electron microscopy (EM).Results EM showed that thickening of the choroid resulted from the invasion of many lymphocytes and epithelioid-like cells. The melanocytes were surrounded by lymphocytes and lost their normal spindle shape. Neutrophils and eosinophils were also present in the choroid. These findings are very similar to the changes reported in eyes from patients with VKH disease or sympathetic ophthalmia.Conclusions The similarity of the ultrastructural changes in this model to those in human VKH disease indicate that this animal model can serve as a histopathological model of human VKH disease. Jpn J Ophthalmol 2004;48:222–227 © Japanese Ophthalmological Society 2004     

血管内皮生长因子及其受体在实验性脉络膜新生血管中的表达

目的 探讨血管内皮生长因子(VEGF)及其FLK1受体在氪激光诱导的棕色挪威(BN)大鼠脉络膜新生血管(CNV)中的表达。方法 应用氪激光对30只雄性BN大鼠实验眼进行视网膜光凝,创建CNV模型,分别于光凝后3、7、14、21、28及56 d行荧光素眼底血管造影(FFA),处死大鼠后摘除眼球,制作组织病理学标本观察,原位杂交检测VEGFmRNA,免疫组化检测VEGF和FLK1受体。结果 正常BN大鼠视网膜神经节细胞层、内核层、色素上皮层、视网膜及脉络膜血管内皮细胞中均表达VEGFmRNA。实验眼光凝后3 d,光凝区视网膜神经节细胞层、内核层、外核层缺损区、视网膜及脉络膜血管内皮细胞均表达VEGFmRNA,此时视网膜下未形成CNV;3-21 d视网膜内VEGFmRNA表达水平逐渐下降(P<0.01);21 d与28 d和56 d比较,VEGFmRNA表达水平差异无显著意义(P>0.05)。光凝后7 d,FFA检查可见光凝区有圆盘状荧光素渗漏。病理切片可见视网膜下形成CNV,CNV中VEGFmRNA表达阳性;7～21 d,CNV中VEGFmRNA阳性染色面积及吸光度(A)值逐渐增加(P<0.01);21 d后VEGFmRNA表达水平差异无显著意义(P>0.05)。正常视网膜和脉络膜血管内皮细胞及视网膜神经节细胞层FLK1受体表达阳性;光凝后7 d,CNV中FLK1受体表达阳性;随CNV的增生,FLK1受体阳性染色面积及A值逐渐增加(P<0.01);21 d与28 d和5     

Immunohistochemical characterization of dendritic cells and macrophages in the aqueous outflow pathways of the rat eye.

Immunohistochemical studies were performed to determine the distribution, phenotype and ontogeny of macrophages and dendritic cells (DCs) in the aqueous humour outflow pathways of the rat eye. Optimal fixation and indirect immunoperoxidase techniques were employed in conjunction with a panel of mAbs on tangential frozen sections of ocular tissues from a total of 37 Wistar Furth rats aged 12-13 days (n = 8), 3 weeks (n = 12), 7 weeks (n = 5) and 15 weeks (n = 12). The density of immunopositive cells was scored qualitatively. A moderate to low density of Ia+ cells with a dendritic morphology were observed in the trabecular meshwork. DCs were also identified in the suprachoroidal space and in the connective tissues of nerves and vessels piercing the sclera, i.e. in association with non-conventional aqueous outflow pathways. The phenotypical and morphological characteristics of these cells would indicate that they may potentially act as antigen presenting cells (APCs). Non-dendritic pleomorphic cells with a macrophage phenotype were also identified in the trabecular meshwork, and bipolar or elongated cells with a macrophage phenotype were a noticeable feature in the perivascular region of collector channels and the limbal episcleral veins. Some macrophage and DC-like cells were observed in intimate association with limbal mast cells. Theories on the mechanisms of Anterior Chamber Associated Immune Deviation (ACAID) have assumed APCs are largely absent from the tissues lining the anterior chamber. Our findings of a low but moderate density of putative APCs in the conventional and non-conventional aqueous humour outflow pathways are discussed in relation to the various theories of ACAID.     

大鼠自身免疫性葡萄膜视网膜炎眼部细胞因子信号抑制因子的表达

目的:大鼠自身免疫性葡萄膜视网膜炎(experimentalautoimmune uveoretinitis,EAU)大鼠模型眼部研究细胞因子信号抑制因子(suppressor of cytokine signaling,SOCS)的表达。方法:用光感受器间维生素A类结合蛋白(interphotoreceptorretinoid-binding protein,IRBP)免疫Lewis鼠160只后,在眼组织切片上应用SOCS多克隆抗体进行免疫组织化学染色,观察其在眼组织中的表达并与正常大鼠40只做对照。结果:用IRBP免疫Lewis鼠后,免疫组织化学染色发现在虹膜、睫状体和视网膜部位可见SOCS-1和SOCS-5蛋白表达;而在正常Lewis鼠未见SOCS蛋白表达。统计学结果显示,SOCS-1和SOCS-5蛋白表达与EAU严重程度呈正相关(r1=0.954,r2=0.963,P<0.01)。结论:自身免疫性葡萄膜视网膜炎Lewis鼠出现SOCS阳性表达细胞在EAU的发病过程中起了一定的作用。     

实验性自身免疫性葡萄膜视网膜炎中浸润细胞的表型及其凋亡的研究

目的探讨实验性自身免疫性葡萄膜视网膜炎(experimental autoimmune uveoretinitis,EAU)中参与的细胞表型及其凋亡。方法用光感受器间维生素A类结合蛋白(interphotoreceptor retinoid-binding protein,IRBP)免疫16只Lewis鼠后，于眼组织切片和平片上进行免疫组织化学染色和原位 凋亡染色，所用抗体为抗单核细胞、巨噬细胞(EDI)、MHC-II类抗原(OX6)、T淋巴细胞(R73)的单克隆抗体，所用原位凋亡试剂盒为TACS1 Klenow。结果用IRBP免疫Lewis鼠后，16只鼠中12只发生了临床可见的葡萄膜炎，炎症平均得分为1.29±0.7级；免疫组织化学染色发现葡萄膜和视网膜中有大量的单核细胞、淋巴细胞及MHC-II⁺细胞浸润，这些组织中均可见浸润细胞的凋亡，虹膜睫状体中凋亡细胞明显多于脉络膜和视网膜中的凋亡细胞。结论单核巨噬细胞、淋巴细胞和MHC-II⁺细胞均参与了EAU的形成，在EAU早期即有浸润细胞发生凋亡，此可能是导致这种炎症迅速消退的重要机制。（中华眼底病杂志，2000，16：1-70）     

Morphometric changes of the choriocapillaris and the choroidal vasculature in eyes with advanced glaucomatous changes

PURPOSE: In addition to an elevated intraocular pressure a compromise of the ocular blood supply have been implicated in the pathogenesis of primary open-angle glaucoma. The purpose of this study was to quantify morphologic changes in the choroid including choriocapillaris thickness and density and diameter of large choroidal vessels in post mortem eyes with advanced primary open-angle glaucoma. METHODS: We analyzed 20 eye bank eyes (provided from the Georgia Eye Bank in Atlanta) with end stage primary open-angle glaucoma and compared them with 20 age-matched control eye bank eyes. The eyes were processed for light microscopy and following variables were measured with a digital filar micrometer: density and diameter of large choroidal vessels in the macular and equatorial choroid; thickness of the choroid in the macular and equatorial region; density and thickness of choriocapillaris in the macular, peripapillary, and equatorial choroid; and peripapillary capillary-free area nasal and temporal to the optic disk. RESULTS: Eyes with glaucoma displayed a lower density of the capillaries of the choriocapillaris as compared to control eyes in the macular, temporal peripapillary, and equatorial choroid with 0.50-0.55 (p=0.018), 0.46-0.51 (p=0.016), and 0.50-0.55 (p=0.038), respectively. There was no significant difference for the choriocapillaris density in the nasal peripapillary choroid, the thickness of the capillaries of the choriocapillaris in all assessed locations, and the nasal and temporal peripapillary capillary-free zone of the choriocapillaris between eyes with glaucomatous damage and controls. Assessment of large choroidal vessels in the macular choroid showed that eyes with glaucoma had a decreased density of veins (11.7-38.9 mm(-2); p<0.001) and arteries (7.7-12.4 mm(-2); p=0.005) and arteries with a higher diameter (45.6-28.2 microm; p<0.001) as compared to control eyes. The large vessels in the equatorial choroid displayed no significant difference in diameter but a lower density (21.2-44.1 mm(-2); p=0.017) in eyes with glaucomatous damage as compared to controls. CONCLUSION: Eyes with advanced glaucomatous damage after long standing primary open-angle glaucoma exhibit several changes including decreased density of capillaries of the choriocapillaris and decreased density of large choroidal vessels. We cannot conclude from our study whether the observed vascular changes in the choroid are primary pathogenic factors or secondary phenomena.     

A Potential Role of Acute Choroidal Expansion in Nonarteritic Anterior Ischemic Optic Neuropathy

PurposeNonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects.MethodsUsing a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch''s membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or “pathological,” conditions. We considered choroidal expansion (c. 35 µL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position.ResultsSupra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a “blunt” choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively.ConclusionsAcute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.     

Effects of cigarette smoking on ocular circulation chronic effect on choroidal circulation]

The effects of long-term smoking on choroidal circulation were studied. For this purpose, Wistar rats were made to inhale mainstream smoke for 30 minutes daily. After periods of inhalation (16 weeks and 25 weeks), choroidal blood flow (CBF) was measured by the hydrogen clearance method and the index of choroidal vascular resistance (systolic tail arterial pressure/CBF) was calculated. There was no significant difference in CBF between either smoking group (16 weeks and 25 weeks) and controls. However the index of choroidal vascular resistance increased significantly after inhalation of smoke for 25 weeks. No histopathological abnormalities were detected in the choroid and outer layer of the retina. The results suggested that long-term smoking might induce disturbance of choroidal circulation.     

Pathogenesis of laser-induced choroidal subretinal neovascularization.

The early stages (1 day to 3 weeks) in the development of laser-induced choroidal subretinal neovascularization were studied in the monkey eye. Histopathology revealed that the intense laser beam disrupted the choroid/Bruch's membrane/retinal pigment epithelium (RPE) complex and initiated a repair process. Although all lesions received the same energy density, the initial choroidal wound varied among the lesions: in some, the necrotic choroid was surrounded by hemorrhagic retinal detachment with RPE denudation; in others, the necrotic choroid was surrounded only by minimal damage to the RPE monolayer. Formation of the choroidal wound was followed by an inflammatory response. Later, newly formed choroidal tissue filled the wound and continued to proliferate towards the subretinal space. RPE cells from the edges of the wound proliferated over the newly formed subretinal tissue and closed the wound. In lesions with a large area of damaged RPE, coverage of the wound was slow; fluid accumulated in the subretinal space, and the lesions demonstrated pooling of fluorescein on angiography (leaky lesions). In lesions with minimal damage to RPE monolayer, closure of the wound was rapid, and the proliferating choroidal tissue did not reach the subretinal space. There was no subretinal fluid accumulation and no pooling of fluorescein on angiography (nonleaky lesions). Our results indicate that both the amount of damage of the choroid/Bruch's membrane/RPE complex and the ability of RPE cells around the damaged area to proliferate and restore the continuity of the RPE layer determine the evolution of newly formed choroidal fibrovascular tissue into a subretinal membrane with or without pooling.     

氪激光诱发大鼠脉络膜新生血管的基因表达谱

目的研究氪激光诱发大鼠脉络膜新生血管的基因表达谱。方法对氪激光诱发BN大鼠脉络膜新生血管的脉络膜组织和正常BN大鼠的脉络膜组织进行总RNA的提取,将纯化后的mRNA进行逆转录制备杂交探针,应用含有5705条Oligo DNA的表达谱芯片对氪激光诱发BN大鼠脉络膜新生血管的脉络膜组织和正常BN大鼠的脉络膜组织进行差异表达谱分析。结果在氪激光诱发BN大鼠脉络膜新生血管的基因表达谱中差异表达基因共有46条,其中上调的基因3条,下调的基因43条。它们分别是物质转运、信号传导、代谢、发育、分化、细胞黏附相关基因。结论氪激光诱发脉络膜新生血管的发生发展涉及多基因改变。（中华眼科杂志,2005,41：317-320）     

Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate

We have developed nanoparticles (NPs), which are capable of targeting a specific lesion and gradually releasing the agent at the site over a prolonged time period after a single intravenous administration. In this study, we evaluated the effects of intravenously administered poly(lactic acid) nanoparticles encapsulating betamethasone phosphate (BP-PLA NPs) on experimental autoimmune uveoretinitis (EAU) in Lewis rats. To determine the localization of NPs within the retina and choroid of rats with EAU, rhodamine (Rh)-encapsulated PLA NPs were injected intravenously and visualized by confocal microscopy. After the disease onset of EAU induced by S-antigen peptide in Lewis rats, either BP-PLA NPs, BP, or saline was injected intravenously, and the eyes were obtained 7 days following treatment and the histological score was determined. The clinical course of EAU was examined using pathological findings and the expression of the glial fibrillary acidic protein, rod opsin, and the surface markers of inflammatory cells (ED1 and pan T-cell) were immunohistochemically determined. Furthermore, T-cell proliferation and delayed-type hypersensitivity (DTH) to S-antigen were assessed. Intravenously injected Rh-PLA NPs accumulated in the retina and choroid of rats with EAU within 3 hr and remained over the succeeding 7-day-period. Furthermore, systemically administered BP-PLA NPs reduced the clinical scores of rats with EAU in 1 day, which were maintained for 2 weeks and decreased the histological scores. In addition, the ocular infiltration of activated T-cells and macrophages in addition to the hypertrophy of Müller cells were markedly reduced with this treatment. Meanwhile, T-cell proliferation and DTH of BP-PLA NPs-treated rats against S-antigen peptide were not significantly different from those of saline-treated rats. Systemically administered BP-PLA NPs inhibit the development of EAU due to the targeting and the sustained release of steroids in situ. The results of these studies suggest that the systemic administration of BP-PLA NPs may lead to a new therapeutic strategy in controlling intraocular inflammation.     

基于OCTA观察眼底不同分期的2型糖尿病患者黄斑区脉络膜及视网膜血流密度变化

目的 应用光学相干断层扫描血管成像(OCTA)观察眼底不同分期的2型糖尿病患者黄斑区脉络膜和视网膜血流密度变化。方法 收集蚌埠医学院第一附属医院2型糖尿病患者150例150眼纳入研究,依据国际临床糖尿病视网膜病变(DR)严重程度分级标准将患眼分为5组,无DR组和轻、中、重度非增生型DR(NPDR)组及增生型DR(PDR)组,每组各30例30眼。OCTA对所有受试者行黄斑部6 mm×6 mm区域的扫描,测量视网膜浅层、深层和脉络膜毛细血管层的血流密度,观察不同分期DR患者脉络膜及视网膜血流密度的变化,分析血流密度与病变程度的相关性。结果 随着DR患者的严重程度加深,视网膜浅层、深层和脉络膜毛细血管层血流密度均呈显著减少趋势(均为P<0.001);但不同分层血流密度中,中度NPDR组与重度NPDR组比较差异均无统计学意义(P=0.216、0.896、0.350)。视网膜浅层、深层和脉络膜毛细血管层血流密度与病变程度均呈正相关(均为P<0.001)。视网膜深层血流密度识别DR严重程度的能力(敏感性和特异性分别为92.5%和93.1%)优于视网膜浅层和脉络膜毛细血管层。结论 OCT...     

凋亡抑制基因survivin在脉络膜黑色素瘤中的表达及意义

目的探讨凋亡抑制基因survivin在脉络膜黑色素瘤中的表达及其临床意义。方法应用免疫组织化学方法检测51例脉络膜黑色素瘤和10例正常脉络膜组织中survivin蛋白表达情况,分析影响survivin表达的病理因素及预后关系。结果Survivin在正常脉络膜组织中呈阴性表达,51例脉络膜黑色素瘤标本中,34例呈阳性表达（66.67%）,脉络膜黑色素瘤组织中survivin的表达显著高于正常组织（P〈0.01）。Survivin阳性表达率与脉络膜黑色素瘤患者肿瘤位置、肿瘤大小无关（P〉0.05）,而与肿瘤细胞类型、是否侵犯巩膜有关（P〈0.05）。结论Survivin在脉络膜黑色素瘤组织中呈阳性高表达,并与预后相关的临床病理指标之间有密切关系,提示survivin在脉络膜黑色素瘤的发生发展中可能起重要作用。