[A case of ring melanoma found while treating traumatic glaucoma].

BACKGROUND: Ring melanoma, a malignant melanoma which infiltrates over 180 degrees degrees of the ciliary body is very rare in Japan. We report a case of ring melanoma found while treating treatment of traumatic glaucoma with an ultrasound biomicroscope (UBM). CASE: A 44-year old woman presented with high intraocular pressure after blunt trauma in her left eye. CLINICAL FINDINGS: Best-corrected visual acuity OS was 1.2, and intraocular pressure was 30 mmHg. Gonioscopy showed about 180 degrees of the angle recession. Intraocular pressure was difficult to control in spite of anti-glaucoma drug treatment. Rapid progression of iris elevation and 360 degrees thickening of the ciliary body were detected by UBM. We detected atypical cells with melanine granules in the aqueous fluid and positive findings in PET-CT, leading to a diagnosis of ciliary body malignant melanoma. Consequently we enucleated the left eye. The histopathological diagnosis was ring melanoma. CONCLUSION: Ring melanoma is an important element in the differential diagnosis for untreatable secondary glaucoma.

[Long-term surgical results of initial trabeculotomy combined with sinusotomy performed inferiorly].

PURPOSE: To evaluate retrospectively the long-term effects of initial trabeculotomy combined with sinusotomy performed inferiorly. PATIENTS AND METHOD: Enrolled were 128 eyes of 100 patients who received initial glaucoma surgery. In 36 eyes, the removal of Schlemm's canal endothelium was also performed (removed group). The results were compared with the intact group RESULTS: In the primary open angle glaucoma (POAG), mean intraocular pressure (IOP) at 3 years after surgery was 14.6 (intact) and 15.4 mmHg (removed). Kaplan-Meier life-table analysis showed that qualified success rates for the intact group at 8 years were 62.2% and for the removed group at 5 years 45.2% defined by 20 mmHg or lower. The results in developmental glaucoma (DG) were similar to those in POAG. No statistical differences in postoperative IOP between the intact and removed groups were seen in either POAG or DG. In exfoliation glaucoma (XFG), mean IOPs for the intact group at 3 years were 17.3 mmHg and for the removed group at 2 years 15.4 mmHg. The success rates for the intact group at 3.5 years were 25.2% and for the removed group at 4.5 years 64.3%. The results in the intact group were worse than in the POAG patients. Although visual disturbance was seen in 13% of the patients, the major cause was the progression of the cataracts. CONCLUSIONS: The long-term results were the same as those of previous reports on surgery performed superiorly, including the frequency of visual disturbance. However the removal of Schlemm's canal endothelium is necessary in XFG for better IOP control.

Clinical and histopathological features of a suspected case of fish-eye disease.

PURPOSE: To report the clinical and histopathological features of a suspected case of fish-eye disease. CASE: A 57-year-old man presented with blurred vision. The best corrected visual acuity was 0.8 OD and 1.0 OS. The patient had no family history of cloudy cornea. Slit-lamp examination revealed massive bilateral diffuse corneal clouding. Because of progressive corneal clouding during the previous 3 years, we performed penetrating keratoplasty and cataract surgery. He had a low-plasma, high-density lipoprotein (HDL) concentration. Histopathologically, numerous small vacuoles were dispersed, especially in the anterior corneal stroma. An electron microscope revealed distinct 0.2-3.0-µm lipid vacuoles with a conserved stromal structure. CONCLUSION: We suspected a case of sporadic fish-eye disease in a Japanese patient. Lipid deposition needs to be considered as a cause of diffuse corneal opacity.

Intraocular pressure (IOP) reduction by latanoprost in Japanese normal tension glaucoma patients over a five-year period stratified by presenting IOP.

PURPOSE: We examined the effectiveness of latanoprost for reducing intraocular pressure (IOP) in Japanese patients with normal tension glaucoma (NTG) over a 5-year period. DESIGN: Prospective interventional case series. The patients were classified into 2 groups based on mean IOP. METHODS: A total of 38 patients with NTG were studied after being classified into the high-tension (mean IOP 16 mmHg or greater, n = 27) and low-tension (mean IOP lower than 15 mmHg, n = 11) groups. IOP was measured and Humphrey Field Analyzer (HFA) examinations were conducted at 6, 12, 24, 36, 48, and 60 months after beginning a daily administration of latanoprost. RESULTS: Mean IOP before administration was 17.6 mmHg in the high-tension group, which was reduced to 13.9, 14.6, 14.4, 14.1, 13.6, and 14.6 mmHg at 6, 12, 24, 36, 48, and 60 months, respectively, after beginning administration. That in the low-tension group was 13.6 mmHg before administration, and then was reduced to 12.2, 11.4, 11.5, 12.5, 10.5, and 11.5 mmHg, respectively, after beginning administration was noted. Mean deviation (MD) values in the HFA examinations were reduced by -4.27 and -1.49 dB after 5 years in the high- and low-tension groups, respectively. CONCLUSIONS: Latanoprost administration was effective in reducing IOP over a 5-year period in a range of 3.1-4.1 and 1.3-3.6 mmHg in NTG patients with high- and low-tension levels, respectively. In addition, our results indicate that latanoprost helped to prevent a decrease in MD values in both groups, as shown by the results of HFA examinations.

Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab.

PURPOSE: Bevacizumab is a human monoclonal IgG1 antibody that blocks the action of vascular endothelial growth factor (VEGF). The purpose of this study was to determine the level of VEGF and pigment epithelium-derived factor (PEDF) in eyes with proliferative diabetic retinopathy (PDR) before and after an intravitreal injection of bevacizumab. METHODS: Eleven eyes of ten patients were studied. Patients were included if they had neovascular glaucoma, rubeosis of the iris with PDR, or aggressive PDR. Samples of aqueous humor were collected just before the injection of bevacizumab and the vitrectomy. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay, and the effects of bevacizumab on PDR were evaluated. RESULTS: The free VEGF concentration before the injection was 676.5 +/- 186.7 pg/ml (mean +/- SEM, n = 11). Seven days later, it was significantly reduced to 7.1 +/- 7.1 pg/ml (P < 0.005, n = 9). The PEDF concentration before the injection was 2.32 +/- 0.49 microg/ml (n = 11), and 7 days later, it was 3.23 +/- 0.76 microg/ml (P = 0.33). During the vitrectomy, patients had less intraoperative bleeding when the neovascular tissues were cut. CONCLUSIONS: An intravitreal injection of bevacizumab significantly decreased the free VEGF in the aqueous humor by 7 days, indicating that the clinical effects of bevacizumab appear rapidly. However, intravitreal bevacizumab did not affect the level of intraocular PEDF.

Relationship between pigment epithelium-derived factor (PEDF) and renal function in patients with diabetic retinopathy.

PURPOSE: Diabetic retinopathy and nephropathy are microvascular complications in patients with diabetes that are considered to be related. Pigment epithelium-derived factor (PEDF), a strong inhibitor of angiogenesis, is significantly elevated in the blood of diabetic patients, especially those with proliferative diabetic retinopathy (PDR). The level of PEDF in the blood, on the other hand, is reported to be low in a diabetic nephropathy. The aim of this study was to determine the relationship between PEDF and renal function in patients with diabetic retinopathy. METHODS: A total of 243 type 2 diabetic patients were studied. The relationship between the diabetic retinopathy and levels of PEDF, HbA1c, blood urea nitrogen (BUN), and creatinine were evaluated. RESULTS: The mean plasma PEDF level in patients with PDR (7.69+/-6.14 microg/ml; mean+/-standard error) was significantly higher than that of mild-to-moderate nonproliferative diabetic retinopathy (5.07+/-4.37 microg/ml, p=0.02). The level of BUN and creatinine increased significantly as the stage of diabetic retinopathy advanced. The plasma PEDF levels were significantly correlated with the levels of BUN and creatinine (r=0.54, p<0.0001; r=0.57, p<0.0001, respectively). CONCLUSIONS: The levels of plasma PEDF increases with advances in both diabetic retinopathy and nephropathy. Thus, increased levels of PEDF in the blood may indicate microvascular damages in diabetic patients and may be predictor of the progression of retinopathy and nephropathy.

Hypericin inhibits pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy.

PURPOSE: Ocular neovascularization is a leading cause of blindness in ischemic retinopathies. Hypericin is an active ingredient in the medical herb St. John's Wort (SJW). Because hypericin inhibits intracellular signaling pathways that are believed to participate in the regulation of angiogenesis, we investigated the actions of hypericin and SJW in retinal neovascularization, using a mouse model of oxygen-induced retinopathy (OIR). METHODS: C57BL/6 neonatal mice were exposed to a 75% concentration of oxygen from postnatal day 7 (P7) to P12 and returned to room air from P12 to P17 to induce retinal neovascularization. SJW (15 mg/kg/day), hypericin (15, 45, or 135 mug/kg/day), or vehicle was given by gavage once a day for five days from P12 to P17. To quantify the area of retinal neovascularization and vasoobliteration, we stained retinas with isolectin B4 at P17. Phosphorylation of extracellular signal-regulated kinase (ERK) in ischemic retinas was determined by western blot analysis. To estimate retinal vascularization, we stained retinas with isolectin B4 at P7 after treatment with SJW, hypericin, or vehicle from P3 to P7. RESULTS: Gavage administration of hypericin or SJW significantly inhibited the degree of retinal neovascularization, but did not affect the area of retinal vasoobliteration in a mouse model of OIR. Both SJW and hypericin had no effect on normal vascularization over the treatment time course. Treatment with SJW or hypericin reduced phosphorylation of ERK in the retina. CONCLUSIONS: These data suggest that hypericin and SJW reduce pathological retinal neovascularization and that administration of these agents could have clinical utility for treatment of ischemic retinopathies.

Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury.

Vascular endothelial growth factor-A (VEGF-A) has recently been recognized as an important neuroprotectant in the central nervous system. Given its position as an anti-angiogenic target in the treatment of human diseases, understanding the extent of VEGF's role in neural cell survival is paramount. Here, we used a model of ischemia-reperfusion injury and found that VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. Although mechanistic studies suggested that VEGF-A-induced volumetric blood flow to the retina may be partially responsible for the neuroprotection, ex vivo retinal culture demonstrated a direct neuroprotective effect for VEGF-A. VEGF receptor-2 (VEGFR2) expression was detected in several neuronal cell layers of the retina, and functional analyses showed that VEGFR2 was involved in retinal neuroprotection. VEGF-A was also shown to be involved in the adaptive response to retinal ischemia. Ischemic preconditioning 24 hours before ischemia-reperfusion injury increased VEGF-A levels and substantially decreased the number of apoptotic retinal cells. The protective effect of ischemic preconditioning was reversed after VEGF-A inhibition. Finally, chronic inhibition of VEGF-A function in normal adult animals led to a significant loss of retinal ganglion cells yet had no observable effect on several vascular parameters. These findings have implications for both neural pathologies and ocular vascular diseases, such as diabetic retinopathy and age-related macular degeneration.

Plasma concentration of pigment epithelium-derived factor in patients with diabetic retinopathy.

CONTEXT: Pigment epithelium-derived factor (PEDF) is a strong inhibitor of angiogenesis. Eyes with diabetic retinopathy have low levels of ocular PEDF; however, the PEDF levels in the blood of diabetics have still not been determined. OBJECTIVES: Our objective was to determine the plasma levels of PEDF in diabetic patients and to determine the relationship with the stage of the diabetic retinopathy. DESIGN AND SETTING: This study was designed as a cross-sectional, institutional study. PATIENTS OR OTHER PARTICIPANTS: A total of 145 Japanese were studied; 112 had type 2 diabetes mellitus, and 33 were healthy controls. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The plasma level of PEDF was measured by ELISA, and the stage of diabetic retinopathy was determined by ophthalmic examinations. Clinical systemic status of diabetic patients was also examined. RESULTS: The plasma PEDF level in diabetic patients (6.68 +/- 0.54 microg/ml; mean +/- sem) was significantly higher than that in controls (4.38 +/- 0.59 microg/ml, P = 0.03), and the level was especially high in patients with proliferative diabetic retinopathy (7.78 +/- 0.98 microg/ml; n = 45; P = 0.005). The gender (P = 0.03), blood urea nitrogen (P = 0.005), and triglycerides (P = 0.04) were significant and independent determinants of plasma PEDF levels in diabetic patients. CONCLUSIONS: The PEDF level in the plasma was significantly elevated in diabetic patients, especially those with proliferative diabetic retinopathy. High levels of PEDF in the plasma may be related to the progression of diabetic retinopathy.

Pars plana vitrectomy with removal of posterior hyaloid face in treatment of refractory diabetic macular edema resistant to triamcinolone acetonide.

BACKGROUND: Triamcinolone acetonide (TA) has recently been used to treat diabetic macular edema (DME) but its effectiveness is limited. CASES: Three patients (three eyes) with unresolved diffuse DME who did not respond to a posterior sub-Tenon's injection of TA underwent vitrectomy. OBSERVATIONS: Intraoperatively, it was found that all of the eyes had a posterior hyaloid face that was adherent to a large area of the posterior pole retina, although this had not been detected by slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and removal of the posterior hyaloid face, there was a significant reduction in the central macular thickness of all three eyes and an improvement in the visual acuity of the patients. CONCLUSIONS: When TA treatment is not effective for DME, vitrectomy with the complete removal of the posterior hyaloid face, including removal of the internal limiting membrane, should be considered.

Inhibitory effect of an antibody to cryptic collagen type IV epitopes on choroidal neovascularization.

PURPOSE: The wet form of age-related macular degeneration (AMD) occurs as a consequence of abnormal blood vessel growth from the choroid into the retina. Pathological angiogenesis during tumor growth and ocular disease has been associated with specific exposure of cryptic extracellular matrix epitopes. We investigated the presence of cryptic collagen IV epitopes in a murine model of choroidal neovascularization (CNV), and tested the effect on blood vessel growth of H8, a humanized antibody directed against a cryptic collagen type IV epitope. METHODS: To induce experimental CNV in adult C57BL/6 mice, Bruch's membrane was ruptured using a diode laser. Subsequently, mice were treated with daily intraperitoneal (i.p.) injections of either H8 (10 mg/kg or 30 mg/kg) or an isotype-matched antibody control. Two weeks postinjection, choroidal flat mounts were immunostained with the blood vessel marker platelet/endothelial cell adhesion molecule-1 (PECAM-1) and H8. CNV was visualized using fluorescence microscopy and the CNV lesion area measured using Open Lab software. RESULTS: Collagen type IV and the cryptic epitope were observed at the site of laser-induced lesions. Staining with H8 was first observed three days post injury, two days after MMP2 expression in CNV lesions, becoming most intense five days following laser injury and extending beyond the area of neovascularization. At 14 days post injury, H8 staining was reduced in intensity, colocalized with the area of CNV, and was nearly absent from the underlying choroidal vessels. In addition, mice treated with H8 had a significant dose-dependent decrease in the area of CNV as compared to isotype-matched antibody controls. CONCLUSIONS: Results suggest that exposure of cryptic collagen type IV epitopes is associated with the incidence of CNV and that the humanized antibody H8 may provide a new treatment for CNV.

Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization.

'Vascular endothelial growth factor-A (VEGF-A) blockade has been recently validated as an effective strategy for the inhibition of new blood vessel growth in cancer and ocular pathologies. However, several studies have also shown that anti-VEGF therapy may not be as effective in the treatment of established unwanted blood vessels, suggesting they may become less dependent on VEGF-A for survival. The VEGF-A dependence of vessels may be related to the presence of vascular mural cells (pericytes or smooth muscle cells). Mural cell recruitment to the growing endothelial tube is regulated by platelet-derived growth factor-B (PDGF-B) signaling, and interference with this pathway causes disruption of endothelial cell-mural cell interactions and loss of mural cells. We have investigated the basis of blood vessel dependence on VEGF-A in models of corneal and choroidal neovascularization using a combination of reagents (an anti-VEGF aptamer and an anti-PDGFR-beta antibody) to inhibit both the VEGF-A and PDGF-B signaling pathways. We demonstrate that neovessels become refractory to VEGF-A deprivation over time. We also show that inhibition of both VEGF-A and PDGF-B signaling is more effective than blocking VEGF-A alone at causing vessel regression in multiple models of neovascular growth. These findings provide insight into blood vessel growth factor dependency and validate a combination therapy strategy for enhancing the current treatments for ocular angiogenic disease.

In vivo evidence of angiogenesis induced by transcription factor Ets-1: Ets-1 is located upstream of angiogenesis cascade.

BACKGROUND: A transcription factor, ets-1, regulates the transcription of metalloproteinase genes, the activity of which is necessary for matrix degradation and the migration of endothelial cells. However, no study has demonstrated that ets-1 itself has an angiogenic action in vivo. Thus, we examined (1) the effects of overexpression of the ets-1 gene on angiogenesis in a rat hindlimb ischemia model, and (2) how ets-1 induced angiogenesis. METHODS AND RESULTS: In this study, we used the HVJ-liposome method, which is highly effective for transfection, to transfect the human ets-1 gene. At 4 weeks after transfection, the capillary density and blood flow were significantly increased in a hindlimb transfected with the human ets-1 gene compared with control. These data clearly demonstrated that ets-1 has the ability to stimulate angiogenesis in vivo. To elucidate the molecular mechanisms by which ets-1 induced angiogenesis, we focused especially on the expression of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), potent angiogenic growth factors, because the promoter regions of both genes contain ets binding sites. Interestingly, overexpression of ets-1 upregulated both tissue HGF and VEGF concentrations in rat hindlimb. More importantly, administration of neutralizing antibody against HGF and VEGF attenuated the increase in blood flow and BrdU-positive cells induced by ets-1. Upregulation of HGF and VEGF by ets-1 was also confirmed by in vitro experiments using human vascular smooth muscle cells. CONCLUSIONS: The present study demonstrated that ets-1 regulated angiogenesis through the induction of angiogenic growth factors (VEGF and HGF). Overexpression of ets may provide a new therapeutic strategy to treat peripheral arterial disease.

Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets transcription factors.

BACKGROUND: Two phenomena, inflammation and matrix degradation, contribute to the progression of abdominal aortic aneurysm (AAA). Importantly, the inflammation is regulated by the transcription factor nuclear factor (NF)-kappaB, whereas the destruction and degradation of elastin fibers by matrix metalloproteinases (MMP) are regulated by ets. Thus, we developed a novel strategy to treat AAA by simultaneous inhibition of both NF-kappaB and ets by using chimeric decoy oligodeoxynucleotides (ODN). METHODS AND RESULTS: AAA was induced in rats by transient aortic perfusion with elastase, whereas transfection of decoy ODN was performed by wrapping a delivery sheet containing decoy ODN around the aorta. Gel-mobility shift assay at 7 days after treatment demonstrated that both NF-kappaB and ets binding activity were simultaneously inhibited by chimeric decoy ODN. Transfection of chimeric decoy ODN resulted in significant inhibition of the progression of AAA such as aneurysmal dilation at 4 weeks after treatment as compared with control, accompanied by a reduction of MMP expression. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with chimeric decoy ODN. Importantly, transfection of chimeric decoy ODN demonstrated potent inhibition of aneurysmal dilatation compared with NF-kappaB decoy ODN alone, whereas scrambled decoy ODN had no effects. Interestingly, the migration of macrophages was significantly inhibited by chimeric decoy ODN. CONCLUSIONS: We demonstrated that inhibition of the progression of AAA was achieved by a novel strategy with chimeric decoy ODN used against NF-kappaB and ets in rat model. NF-kappaB and ets are considered to play an important role in the pathogenesis of AAA.

Upregulation of chemokine expression in the retinal vasculature in ischemia-reperfusion injury.

PURPOSE: To evaluate chemokine expression at various retinal sites after ischemia-reperfusion injury, using reverse transcription-polymerase chain reaction (RT-PCR) analysis of selected tissue obtained by laser capture microdissection. METHODS: Retinal ischemia was produced in Lewis rats by increasing intraocular pressure for 75 minutes. At 3, 6, 12, and 24 hours after reperfusion, RT-PCR was used to measure the levels of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin (IL)-8, and interferon-gamma-inducible 10-kDa protein (IP-10) mRNA expression in the ganglion cell layer (GCL), inner nuclear layer (INL), outer nuclear layer (ONL), and retinal vessels, after laser capture microdissection of these retinal layers. These chemokines were further localized by immunohistochemical methods, using antibodies specific to MCP-1 and MIP-1alpha. Leukocyte infiltration into the retina was detected with immunostaining for leukocyte common antigen. RESULTS: Ischemia-reperfusion induced expression of MCP-1, MIP-1alpha, and MIP-1beta mRNA in the retinal vessels 3 hours after reperfusion. Six hours after reperfusion, expression of these chemokines and IL-8 mRNA was seen in the GCL and INL. Twelve hours after reperfusion, IP-10 mRNA expression was seen in the GCL and INL. Immunoreactive MCP-1 and MIP-1alpha were detected in the GCL, INL, and the retinal vessels 24 hours after reperfusion. No chemokine mRNA expression or immunoreactivity was detected in the ONL at any time. Leukocyte infiltration was noted at 12 hours, increasing markedly 24 hours after reperfusion. CONCLUSIONS: Ischemia-reperfusion retinal injury results in generation of highly chemotactic agents, initially in the retinal vasculature, then in the other inner retinal layers. Such differential chemokine expression may play a role in leukocyte recruitment and selective leukocyte infiltration in the inner retina, leading to retinal damage primarily localized to the ganglion cells and other inner neuronal structures.

Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF). METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically. RESULTS: In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization. CONCLUSIONS: PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.

Effective transfection of a cis element "decoy" of the nuclear factor-kappaB binding site into the experimental choroidal neovascularization.

PURPOSE: To evaluate the efficacy of the gene transfer of a double-stranded phosphorothioate oligonucleotides (ODNs), called a "decoy", against the NF-kappaB binding site into cells of an experimentally-induced choroidal neovascularization. METHODS: FITC-labeled decoy was injected into the subretinal space of rat eyes by the HVJ-liposome delivery system, and 3 days later, choroidal neovascularization was induced by laser photocoagulation. The eyes were removed and the transfected cells were detected by fluorescence microscopy and also detected by immunohistochemistry. The degree of neovascularization was evaluated by fluorescein angiography. RESULTS: The decoy was transfected into the retinal pigment epithelial (RPE) cells, inner and outer segment of the photoreceptors at 3 days after the injection. When choroidal neovascularization was induced, highly effective transfection of the decoy was observed 3 to 14 days after photocoagulation, after which the level decreased. Decoys were transfected into the RPE cells and macrophages in the choroidal neovascularization. The eyes transfected with NF-kappaB decoy showed a weaker leakage in fluorescein angiograms than that of the control eyes transfected with scrambled decoy. CONCLUSIONS: A decoy can be transfected into retinal cells and cells within a choroidal neovascularization by the HVJ-liposome method. The transferred NF-kappaB decoy reduced the degree of choroidal neovascularization. Decoy targeted against NF-kappaB may be considered as a potential therapy for neovascularization.