Detection of eicosanoids in epiretinal membranes of patients suffering from proliferative vitreoretinal diseases

AIM—Arachidonic acid is metabolised via lipoxygenase to 15-HETE (15-hydroxyeicosatetraenoic acid) and 15-HPETE (15-hydroperoxyeicosatetraenoic acid), which are believed to influence proliferation in tissue culture. 15-HETE is the reduction product of 15-HPETE. Cell proliferation is believed to be decreased by 15-HPETE and increased by 15-HETE. The aim of this study was to investigate epiretinal membranes for the presence of these lipoxygenase products and to compare membranes from different disease processes.
METHODS—Epiretinal membranes of 15 patients suffering from proliferative vitreoretinopathy (PVR, n=7) and proliferative diabetic retinopathy (PDR; n=8) were removed during vitrectomy and analysed by means of thin layer chromatography. The plates were evaluated by digital image analysis.
RESULTS—Both 15-HETE and 15-HPETE were identified in membranes from eyes of patients with PVR and PDR with HETE values significantly higher (p<0.05) than HPETE values (HETE/HPETE ratio = 5.2).
CONCLUSION—This study demonstrates that eicosanoids are present in the epiretinal membrane tissue of patients with PVR and PDR. Considering that HETE increases cell proliferation while HPETE inhibits it, it is conceivable that eicosanoids are an additional factor contributing to the regulation of membrane growth in proliferative retinal disorders. Thus, inhibition of lipoxygenase could be a therapeutic approach in these diseases.

     

Platelet derived growth factor and fibroblast growth factor basic levels in the vitreous of patients with vitreoretinal disorders

AIM—To determine the potential role of basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) in the pathogenesis of proliferative vitreoretinopathy (PVR).
METHODS—An enzyme linked immunosorbent assay technique was used to determine the quantities of bFGF and PDGF in 38 vitreous samples taken from patients undergoing trans pars plana vitrectomy (PPV) for a variety of vitreoretinal disorders.
RESULTS—bFGF levels ranged from undetectable to 318.7 pg/ml. The mean concentration was 27.57 pg/ml. PDGF levels ranged from undetectable to 160 pg/ml, the mean concentration being 40.06 pg/ml. Eight of 13 patients with clinical evidence of retinal detachment (RD) and PVR had significantly elevated bFGF concentrations, whereas only one of 11 patients with RD and no PVR had detectable bFGF; seven of eight patients with RD and PVR had elevated PDGF concentrations in the vitreous, whereas all 10 patients with RD and no PVR had no detectable vitreous PDGF. Eight patients with vitreous haemorrhage had raised PDGF concentrations, and the levels were particularly high (>120 pg/ml) in those two patients with active neovascularisation. Two out of nine patients with vitreous haemorrhage had raised bFGF levels.
CONCLUSIONS—bFGF and PDGF concentrations are elevated in PVR even in the absence of vitreous haemorrhage, and not in patients with RD uncomplicated by PVR. This observation suggests that both cytokines may be involved in the pathogenesis of PVR.

Keywords: basic fibroblast growth factor; platelet derived growth factor; proliferative vitreoretinopathy     

Intravitreal growth factors in proliferative diabetic retinopathy: correlation with neovascular activity and glycaemic management

AIM—Many growth factors are implicated in proliferative diabetic retinopathy (PDR). It was decided to test the hypothesis that no one factor is predominant but that a regular profile of levels of different growth factors might be operating, and that the profile might differ according to whether or not insulin therapy was part of the patient's glycaemic management. The levels of several growth factors in vitrectomy samples were therefore determined from diabetic patients with tractional, non-haemorrhagic sequelae of PDR and these levels were correlated with (a) each other (growth factor profile), (b) neovascular activity, and (c) the method of glycaemic management (insulin treated (IT) or non-insulin treated (NIT)).
METHODS—72 samples of vitreous were obtained from either diabetic patients with PDR (n = 51) or non-diabetic (control) patients (n = 21). Levels of bFGF, IGF-I, EGF, and insulin were determined by radioimmunoassay; levels of TGF-β2 by ELISA; and levels of IGF-I binding protein by western ligand blotting. The data were analysed using appropriate statistics.
RESULTS—There was no regular growth factor profile. bFGF levels were significantly greater in vitreous from NIT patients compared with IT patients and controls. The highest levels of bFGF were found in NIT patients with actively vascularised membranes. TGF-β2 levels were significantly greater in vitreous from IT patients compared with NIT patients and controls The highest levels of TGF-β2 were found in IT patients with actively vascularised membranes. IGF-I levels were significantly greater in diabetics (irrespective of insulin treatment) than non-diabetics and the highest levels of IGF-I were found in IT patients with actively vascularised membranes. A 34 kDa IGFBP was the predominant IGFBP identified in vitreous and was found to be elevated in diabetics patients.
CONCLUSION—In PDR there is a correlation between intravitreal growth factor levels and both disease state (whether active or fibrotic) and method of glycaemic management.

     

Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression

PURPOSE: To assess the incidence of cell proliferation and apoptosis in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and macular pucker (MP) and to further investigate the potential involvement of key executors of apoptosis. METHODS: Epiretinal membranes were obtained from the eyes of 23 patients who underwent vitrectomy surgery for recurrent retinal detachment due to PVR (n = 16), traction retinal detachment due to PDR (n = 5), and macular pucker (n = 2). Cell proliferation was evaluated by Ki-67 and PCNA (proliferation cell nuclear antigen) immunostaining. Apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transfrase-dUTP-nick end labeling). The expression of caspase-3 and PARP (poly-ADP-ribose-polymerase) was detected using antibodies against activated caspase-3 and p85 fragment of PARP. Cytokeratin and activated caspase-3/PARP, GFAP (glial fibrillary acidic protein) and activated caspase-3/PARP double staining were used to identify cell types in the membranes. RESULTS: There was no statistically significant difference in the cell proliferative index between PVR (70.1 +/- 4.2%), PDR (82.1 +/- 7.0%), and macular pucker (72.9 +/- 22.8%) by multivariate analysis (p = 0.39, ANOVA) and univariate analysis. Apoptotic nuclei were seen more frequently in chronic retinal detachments of greater than 2 months duration, but the difference, compared to shorter term retinal detachments was not statistically significant (p = 0.19). The apoptosis indices determined for PVR (2.3 +/- 0.7%), PDR (3.4 +/- 1.5%) and macular pucker (5.5 +/- 3.2%) were not significantly different (ANOVA, p = 0.41). Apoptotic nuclei were correlated, increased with expression of caspase-3 and PARP. Many apoptotic cells appeared to derive from retinal pigment epithelium cells. CONCLUSIONS: Cell proliferation and apoptosis appear to be key mechanisms regulating certain cell populations in epiretinal membranes of PVR, PDR, and macular pucker. Inhibition of proliferative regulators such as PCNA and/or activation of apoptotic executors such as caspase-3 may serve as therapeutic targets to halt progression of proliferative retinal disorders.     

Silicone assisted, argon laser confinement of recurrent proliferative vitreoretinopathy related retinal detachment: a technique to allow silicone oil removal in problem eyes

AIMS/BACKGROUND—Recurrent peripheral retinal detachments may occur in eyes treated with vitrectomy and silicone oil for retinal detachments complicated by proliferative vitreoretinopathy (PVR). The aim of this study was to assess whether laser photocoagulation could be used in the presence of silicone oil to confine and stabilise recurrent PVR related peripheral retinal detachments enabling the timely removal of the oil.
METHODS—10 patients with recurrent peripheral retinal detachments after vitrectomy and silicone oil insertion were treated with posturing and subsequent focal argon laser to circumscribe the area of recurrent detachment.
RESULTS—This technique alone was sufficient to limit the area of retinal detachment in seven of the cases. The remaining three cases required relieving retinotomies because of increasing retinal detachment despite the laser. In all 10 cases the silicone oil was later removed without progression of the detached areas.
CONCLUSION—Silicone assisted argon laser `confinement' can be effective in stabilising eyes with peripheral retinal detachments allowing the subsequent removal of silicone oil.

     

Late reopening of successfully treated macular holes

BACKGROUND—Most idiopathic macular holes can be closed by a surgical procedure combining vitrectomy, posterior hyaloid ablation, and fluid-gas exchange followed by postoperative positioning. Reopening of closed macular holes has been reported, but its frequency is not known. Here the incidence of reopening after successful macular hole surgery is reported.
METHODS—77 consecutive cases of idiopathic macular holes operated with autologous platelet injection between July 1993 and October 1995 were reviewed. The procedure consisted of three port vitrectomy, posterior hyaloid removal, non-expansile fluid-gas exchange, and autologous platelet injection followed by face down positioning. The incidence of reopening was analysed in the cohort of the 72 anatomical successes.
RESULTS—Mean follow up was 12.3 months. The macular hole reopened in five eyes of five patients (five out of 72 patients, 6.9%), in four cases after cataract extraction. In four cases too, an epiretinal membrane was noted, either clinically or during reoperation, and fluorescein leakage in the macular area was present in two cases. Three of the five cases of reopening were reoperated and all three were anatomical successes.
CONCLUSION—Late macular hole reopening occurred in five out of 72 patient, and in four cases after cataract surgery. The presence of an epiretinal membrane around the hole in four of them suggested that tractional forces were responsible for the reopening. Reoperation, performed in three cases, again closed the macular holes.

     

Complicated posterior capsulorhexis: aetiology, management, and outcome

BACKGROUND—A 1 year retrospective analysis of 650 patients, who underwent a posterior capsulorhexis on their intact capsules, was performed to examine the incidence of complications, their aetiologies, and the outcome.
METHODS—Data were analysed on 32 patients with complicated capsulorhexis for type of surgery, preoperative and postoperative factors, and relative risk factors for vitreous issue.
RESULTS—There were six patients with vitreous loss. The posterior capsulorhexis was uncontrolled in 14 cases and difficult to perform in 12 cases. Implantation into the capsular bag was possible in all cases. Systemic vascular hazard and old age (over 80 years) were found to be statistically significant risk factors for vitreous loss (p=0.002 and p=0.03 respectively). The mean follow up was 13.5 months (range 4-25 months). One patient developed a retinal detachment and two had a transient clinical cystoid macular oedema. Visual acuity of ≥ 20/40 was obtained in 93% of the patients.
CONCLUSION—Loss of control of the posterior capsulorhexis has a low incidence but can lead to serious problems during surgery. A good knowledge of the technique is necessary to complete the procedure with a posterior capsulorhexis of the optimum size without vitreous loss.

     

Vascular endothelial growth factor levels in vitreous and serum of patients with either proliferative diabetic retinopathy or proliferative vitreoretinopathy

PURPOSES: To confirm the role of vascular endothelial growth factor (VEGF) in the pathogenesis of proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) and to investigate the relationship between the level of VEGF in serum and its vitreal level in patients with either disease. METHODS: Venous blood and vitreous of 18 patients with PDR, 15 patients with PVR and 20 patients forming a control group were collected during vitrectomy. The VEGF level was quantified by using ELISA methods in either serum or vitreous. RESULTS: The VEGF level in serum and vitreous was similarly high in the case of PDR, but its level was only high in serum in the case of PVR. DISCUSSION: PDR is closely linked with systemic diabetes mellitus whereas PVR is more localized. More selective systemic anti-VEGF medications with reduced side effects are required to treat PDR successfully.     

Local hypothermia protects the retina from ischaemic injury in vitrectomy

AIMS—Hypothermic irrigating solutions were used during vitrectomy in pressure induced ischaemic eyes so that their effects on retinal function and histological changes could be investigated.
METHODS—After anaesthetised albino rabbits underwent closed vitrectomy, their vitreous cavities were continuously irrigated for 30 minutes at a perfusion pressure of 140 mm Hg. The rabbits were divided into three groups according to their intraocular perfusion temperatures—8°C, 22°C, and 38°C. Electroretinograms were taken before and after irrigation. Glutamate levels in the vitreous were examined after irrigation. Eyes were enucleated on the seventh postoperative day and examined histologically.
RESULTS—On the seventh postoperative day, the recovery rate of a-wave amplitudes was significantly lower in the 38°C group than in the 8°C group, and that of b-wave amplitudes was significantly lower in the 38°C group than in either the 8°C or 22°C group. Retinal damage in the 38°C group revealed more severe histological impairment than in either the 8°C or 22°C group. Oedema of the inner retinal layer was significant in both the 22°C and 38°C groups. Glutamates reached peak values 30 minutes after the end of ischaemia in the 38°C group. However, no significant glutamate increases were detected 15 to 60 minutes after ischaemia in either the 8°C or 22°C group.
CONCLUSION—Local hypothermia during vitrectomy in acute ischaemic eyes appears to decrease retinal damage.

     

Vitreous intercellular adhesion molecule 1 in uveitis complicated by retinal detachment

AIMS—The vitreous levels of soluble intercellular adhesion molecule 1 (sICAM-1) were investigated in uveitic eyes undergoing vitrectomy for retinal detachment (RD) or other complications, and the presence of this molecule was related to disease activity and vitreous levels of the cytokine tumour necrosis factor α (TNFα), known to upregulate ICAM-1 expression on various cells.
METHODS—Vitreous and serum samples from 23 patients with either active or quiescent uveitis undergoing retinal surgery were examined for the levels of immunoreactive sICAM-1 and TNFα by ELISA methods, and for the presence of biologically active TNFα. Vitreous from non-uveitic eyes with rhegmatogenous retinal detachment (RRD), macular holes or cadaveric eyes were used as controls.
RESULTS—As a whole, vitreous from uveitic eyes complicated or uncomplicated by RRD contained significantly higher levels of sICAM-1 than vitreous from non-uveitic eyes with RRD alone (p < 0.0005), eyes with macular holes (p< 0.0001), or normal cadaveric vitreous (p < 0.0001). The proportion of vitreous containing >20 ng/ml sICAM-1 (> four times the normal values) was significantly higher in eyes with uveitis complicated by RRD than in those eyes without RRD (Fisher's test, p= 0.02), and although levels of sICAM-1 were higher in eyes with active uveitis than in those with quiet disease (p < 0.02), this could not be dissociated from the increase caused by RRD. There was a relation between the vitreous levels of sICAM-1 and those of immunoreactive TNFα (Spearman's correlation coefficient; r = 0.601, p = 0.006), but not between the vitreous levels of sICAM-1 and those of biologically active TNFα.
CONCLUSION—Increased vitreous sICAM-1 levels and the association of this molecule with the presence of immunoreactive TNFα in uveitic eyes confirm the operation of cytokine mediated vascular reactions at the blood-retinal barrier during the development of this condition. The persistence of high vitreous levels of sICAM-1 in eyes with uveitis complicated by RRD despite previous immunosuppression may indicate a low rate of clearance of inflammatory molecules from the vitreous cavity and an exacerbation of the existing inflammatory process by the retinal detachment itself.

Keywords: vitreous; retinal detachment; ICAM-1; TNFα; uveitis     

Ocular non-Hodgkin's lymphoma: a clinical study of nine cases

BACKGROUND—Primary oculocerebral large cell malignant non-Hodgkin's lymphoma, formerly called ocular reticulum cell sarcoma, runs a uniformly fatal course. Once the central nervous system (CNS) is involved, survival without treatment is very limited. Although treatment does not substantially improve the long term survival, it provides short term improvement in these patients.
METHODS—The charts of all patients with ocular involvement of non-Hodgkin's lymphoma followed during the period 1984-93 were reviewed. The diagnosis of non-Hodgkin's lymphoma was made by different diagnostic approaches: CNS biopsy, anterior chamber tap, vitrectomy, haematology, and necropsy.
RESULTS—Eight patients had oculocerebral large cell and one had small cell non-Hodgkin's lymphoma. Five patients with pure ocular localisation had initially received steroid treatment for intermediate uveitis. First diagnosis was made on CNS biopsy in three, anterior chamber tap in one, vitreous aspirate in three, haematology in one, and necropsy in one case.
CONCLUSION—Ocular non-Hodgkin's lymphoma is a difficult diagnosis. Vitrectomy allows cytological diagnosis in most but not all cases. When no treatment is given, patients survive for only a few weeks once the CNS is involved. Although the disease is eventually fatal, treatment by means of radiotherapy, steroid administration, and vitrectomy can allow these patients to lead a normal professional and social life during the years between recurrences.

     

The Clinical Features of Macular Pucker Formation after Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment Repair

Purpose

To investigate the incidence and predisposing factors of macular pucker formation after pars plana vitrectomy in patients who developed primary rhegmatogenous retinal detachment.

Methods

We retrospectively reviewed a consecutive series of 284 eyes in 284 patients who underwent primary retinal detachment repair by pars plana vitrectomy alone between January 1, 2009 and December 31, 2010. Patients with a history of retinal surgery or another visually significant ocular problem were excluded.

Results

Postoperatively, of the 264 eyes that completed at least six months of follow-up, 16 (6.1%) eyes developed obvious macular pucker at clinical examination. Of these 16 eyes, ten (70.0%) underwent repeat vitrectomy with membrane peeling for macular pucker removal during the follow-up period. The mean time from primary vitrectomy for the retinal reattachment to the secondary vitrectomy with membrane peeling for macular pucker was 7.9 months. The mean improvement in vision after membrane peeling surgery was 0.37 (logarithm of the minimum angle of resolution). Using an independent t-test, chi-square test, and Mann-Whitney U-test, we found that the number or size of retinal break and vitreous hemorrhage could be significant risk factors of macular pucker.

Conclusions

In our study, 6.1% of eyes which underwent pars plana vitrectomy alone for primary retinal detachment developed a postoperative macular epiretinal membrane. Multiple or large retinal breaks and postoperative vitreous hemorrhage were related to macular pucker formation. Overall, the 70.0% of eyes which underwent secondary vitrectomy with membrane peeling for removal of macular pucker showed a favorable visual outcome.     

Proliferative activity in epiretinal membranes. The use of the monoclonal antibody Ki-67 in proliferative vitreoretinal diseases.

Epiretinal membranes occur in a number of pathogenetically different diseases, such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), macular pucker, and ischemic, inflammatory, and degenerative vitreoretinal disorders. The formation of epiretinal membranes is characterized by the proliferation of histogenetically different cell types. Knowledge of the proliferating potential of surgically excised epiretinal membrane tissue might be clinically relevant to determine which patients face a high risk of recurrences. The monoclonal antibody Ki-67 specifically stains a cell-cycle associated nuclear antigen that is only expressed by cells in the G1, S, and G2/M phases of the cell cycle. With this antibody, the actively proliferating growth fraction can be stained in frozen tissue samples of surgically removed epiretinal membranes by the indirect immunoperoxidase method. In this study, the monoclonal antibody Ki-67 was used to screen 37 epiretinal membranes in PVR, PDR, macular pucker, and in recurrences after intraocular silicone oil tamponade for the presence of actively proliferating cells. Additionally, the number of Ki-67 positive cells in a section of the membrane was quantitatively set in relation to the total cell number of this section. Thus a proliferative index (PI) was ascribed to each membrane as a decimal quotient. The proliferative indices can be graded into four subgroups for missing or very low (PI less than 0.1), low (PI 0.1-0.3), moderate (PI 0.3-0.6), and high (PI greater than 0.6) proliferative activities. High proliferative activities were found in 4 of 5 PVR membranes, in 9 of 14 PDR membranes, in 6 of 11 recurrent membranes after intraocular silicone oil tamponade, and in 2 of 6 macular pucker membranes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recombinant tissue plasminogen activator in cases with fibrin formation after cataract surgery: a prospective randomised multicentre study

AIMS—This study investigated the effect of tissue plasminogen activator (tPA) in patients with severe intracameral fibrin after extracapsular cataract extraction or phacoemulsification with posterior chamber intraocular lens implantation.
METHODS—A randomised prospective multicentre study was carried out in 86 patients with intraocular fibrin formation 2-8 days after cataract surgery. While the first group (n=41) received only anti-inflammatory drugs, a single anterior chamber injection of tPA (10 µg) as an additional treatment to the standard was given in the second group (n=44). On days 1, 2, 14, and 90 after randomisation, the visual acuities, slit lamp findings, and intraocular pressures were documented in standardised protocols. Efficacy of treatment was judged by the rate of fibrinolysis (primary objective), the frequency of synechiae, and central capsular fibrosis (secondary objectives).
RESULTS—The incidence and quantity of intraocular fibrin were significantly lower in the patients treated with tPA than in the control group (p<0.05). The frequencies of synechiae were reduced by tPA injection. The capsule fibrosis noted after 3 months was significantly lower in the tPA group (p=0.027). No ocular side effects were noted after the tPA injections.
CONCLUSIONS—Lysis of postcataract fibrin formation is accelerated and increased by a single intracameral injection of 10 µg tPA in addition to standard anti-inflammatory treatment. The findings suggest that the tPA injection reduces posterior capsule fibrosis, which still has to be addressed in larger study populations and with a long term follow up.

Keywords: tissue plasminogen activator; cataract surgery; fibrin; fibrinolysis     

Chorioretinal post-transplant lymphoproliferative disorder induced by the Epstein-Barr virus

BACKGROUND—The Epstein-Barr virus (EBV) is responsible for the lymphoproliferative disorders observed in transplanted patients.
METHODS—The case history is described of a 59 year old man with a chorioretinal lesion who had received a single lung transplant and was on immunosuppressive treatment. Immunoglobulin gene rearrangement and EBV detection by polymerase chain reaction (PCR) with semiquantification were used on the vitreous material.
RESULTS—A proliferation of B lymphocytes with a monoclonal subpopulation was found by PCR on the vitreous sample. The large amounts of EBV genomes found in the vitreous suggest that EBV was the cause of the lymphoproliferation. Healing of the lesion was achieved by a decrease in immunosuppressive treatment and the use of nucleotide analogues.
CONCLUSION—The diagnosis of ocular post-transplant lymphoproliferative disorder (PTLD) can be made by PCR on vitreous material. Early diagnosis and treatment can lead to regression of limited monoclonal lesions.

     

Predicting visual outcome after macular hole surgery using scanning laser ophthalmoscope microperimetry

AIMS—To determine if postoperative visual outcome after successful macular hole surgery can be predicted with preoperative scanning laser ophthalmoscope (SLO) microperimetry.
METHODS—A prospective non-comparative study of 16 eyes in 15 patients examined before the surgery.
RESULTS—Visual outcome following macular hole surgery correlated with the "maximum parahole sensitivity", the highest intensity of stimulus to which the patient did not respond to any of the stimuli around the hole. Preoperative visual acuity, duration of the symptoms, size of the macular hole, and the "minimum parahole sensitivity", the lowest intensity to which the patient responded to all the stimuli around the hole, did not correlate significantly with postoperative visual acuity.
CONCLUSION—Preoperative assessment of patients using SLO microperimetry is a good predictor of visual outcome after macular hole surgery.

     

增殖性玻璃体视网膜病变细胞凋亡的信号传导途径研究

目的 :探讨增殖性玻璃体视网膜疾病细胞凋亡的信号传导途径 ,以寻求新的药物治疗途径。方法 :2 3例增殖性玻璃体视网膜病变 (PVR) ,增殖性糖尿病性视网膜病变 (PDR) ,黄斑裂孔 (MH)及黄斑前膜 (MP)的视网膜前膜 (epiretinalmem brane,ERM )由玻璃体切割术中取得。细胞凋亡的情况由terminaldeoxynucleotidyltransfrase dUTP nickendlabeling(TUNEL法 )进行评估。Caspase 3及PARP的表达由特异性抗体抗活性Caspase 3和抗P 85片段的PARP检测。Cytokeratin与抗活性的Caspase 3双染色法进行凋亡细胞类型的鉴别。结果 :大多数发生凋亡的细胞为RPE细胞 ,而凋亡细胞与抗活性Caspase 3和抗P 85片段的PARP表达增加相关。细胞凋亡的数目与发生慢性视网膜脱离 (>2个月 )的病例有关 ,但凋亡系数 (apopto sisindex ,AI)在两组间无显著性差异 (1 4 4 2 9vs 3 2 2 86 ,P =0 1877)。PVR ,PDR ,MP各组的凋亡系数分别为 2 32 5 % ,3 4 2 % ,5 5 % ,P值分别为PPVR&PDR>0 1(0 16 85 ) ,PPDR&MP>0 1(0 5 380 ) ,PPVR&MP>0 1(0 8333)。结论 :此项研究发现细胞凋亡在PVR、PDR、MH及MP发病中的重要调节作用。诱导Caspase 3活性表达可作为一种治疗增殖性视网膜疾病的新的尝试     

Upregulation of RAGE and its ligands in proliferative retinal disease

We sought to study the presence of the receptor for advanced glycation endproducts (RAGE) and its ligands, advanced glycation endproducts (AGEs), S100/calgranulins and amphoterin (high mobility group box 1 protein; HMGB1), in the vitreous cavity and epiretinal membranes (ERMs) of eyes of patients with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Undiluted vitreous specimens were collected from 30 eyes of 30 patients undergoing pars plana vitrectomy for repair of retinal detachment (RD) secondary to PDR (n = 15) or PVR (n = 15). The vitreous samples obtained from 10 eyes undergoing macular hole repair were used as controls. Epiretinal membranes were obtained from eight eyes with PDR and from 10 eyes with PVR. The levels of AGEs in the vitreous were measured using ELISA. The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. The vitreous levels of sRAGE were significantly increased in both PDR and PVR (p < or = 0.05) compared to control vitreous. In both PDR and PVR, the vitreous levels of AGEs (p < or = 0.01), S100/calgranulins (p < or = 0.05), and amphoterin (p < or = 0.01) were also elevated compared to control eyes. Expression of RAGE was detected in six of eight ERMs from eyes with PDR and eight of 10 ERMs from eyes with PVR. Many cells expressing RAGE also expressed vimentin, suggesting a glial cell origin. Ligands for RAGE were also detected in ERMs, with AGEs detected in five eyes with PDR and eight eyes with PVR. Similarly, S100 and amphoterin ERM expression was observed in six eyes with PDR; these ligands were also expressed in ERMs from eyes with PVR (8 and 7 cases, respectively). We conclude that RAGE and its ligands are increased in the vitreous cavity of eyes with PDR and PVR and are present in ERMs of eyes with these proliferative retinal disorders. These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases.     

uPA, tPA and PAI-1 mRNA expression in periretinal membranes

PURPOSE: Formation of periretinal membranes occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) and includes cell migration, proliferation, extracellular matrix formation and tissue contraction, processes in which plasminogen activation (PA) system is involved. METHODS: Twenty PVR, PDR or pucker membranes were examined to identify the cells with cell specific markers and to detect the expression of urokinase (uPA), tissue-type plasminogen activator (tPA) or plasminogen activator inhibitor-1 (PAI-1) by in situ hybridization and by immunohistochemistry. RESULTS: In PVR, uPA, tPA and PAI-1 were expressed by retinal pigment epithelial (RPE) cells, macrophages or retinal glial cells. In PDR, PA components were also expressed by endothelial cells. Semiquantitative analysis in in situ hybridization and immunohistochemistry results demonstrated no notable differences in uPA, tPA or PAI-1 expression between PDR and PVR membranes. CONCLUSIONS: We conclude that local proteolytic activation is involved in extracellular matrix production both in diabetic and non-diabetic membranes.     

Ultrasound biomicroscopic imaging in intermediate uveitis

BACKGROUND—Clinical examination of the region of the eye mainly affected in patients with intermediate uveitis is difficult and often hampered by media opacities. In that perspective ultrasound biomicroscopy (UBM) promises to be a valuable additional diagnostic tool.
METHODS—UBM was performed at a sound frequency of 50 MHz on 26 eyes of 13 patients with intermediate uveitis in order to determine configuration of pars plana, peripheral retina, and vitreous. Findings of ophthalmoscopy with scleral indentation and UBM were compared.
RESULTS—In 18 of 26 eyes pathological structures such as membraneous or fluffy vitreous condensations were identified by UBM. Among these UBM revealed pathological findings which were not visible on funduscopy in nine eyes. Most importantly, vitreoretinal adhesions with traction on the retina were imaged in four eyes. However, in three eyes vitreous opacities being visible on funduscopy were not identified by UBM.
CONCLUSION—UBM seems to be a valuable diagnostic technique for the evaluation of patients with intermediate uveitis. Longitudinal studies will have to determine the relevance of UBM findings for the individual clinical course and their influence on therapeutic decisions.

Keywords: intermediate uveitis; ultrasound biomicroscopy; vitreous opacities