Macular Degeneration: Sakamoto T

Sakamoto T. · No affiliation provided · Nippon Ganka Gakkai Zasshi. · Pubmed #18517003 No free full text.

This publication has no abstract.

Hirakawa M, Tanaka M, Tanaka Y, Okubo A, Koriyama C, Tsuji M, Akiba S, Miyamoto K, Hillebrand G, Yamashita T, Sakamoto T. · Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. · Br J Ophthalmol. · Pubmed #18441173 links to  free full text

Abstract: AIM: To study the relationship between age-related maculopathy (ARM) and exposure to sunlight using an objective method. METHODS: In a case-control study of Japanese men aged > or = 50 years (67 controls without ophthalmic disease and 148 with ARM), those with ARM were separated into groups of early (n = 75) and late (n = 73) ARM. Facial wrinkle length and area of hyperpigmentation, which are considered to be associated with exposure to sun, were measured using imaging with computer-based image analysis. Skin tone was also measured on the upper inner arm, which is not exposed to sun. Early and late ARM association with skin measurements was then evaluated. RESULTS: Significantly more facial wrinkling (p = 0.047, odds ratio 3.8; 95% CI 1.01 to 13.97) and less facial hyperpigmentation (p = 0.035, odds ratio 0.3; 95% CI 0.08 to 0.92) was present in late ARM cases. The relationship between skin tone and ARM risk was not statistically significant. CONCLUSIONS: This objective method showed that lifetime exposure to sunlight is an important factor in the progression of late ARM. An individual's reaction to sunlight exposure may have a role in ARM progression in addition to total lifetime exposure to sunlight.

Shimura M, Nakazawa T, Yasuda K, Shiono T, Iida T, Sakamoto T, Nishida K. · Department of Ophthalmology, NTT East Japan Tohoku Hospital, Sendai, Miyagi, Japan. · Am J Ophthalmol. · Pubmed #18328456 No free full text.

Abstract: PURPOSE: To compare the effect of an intravitreal injection of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, with that of triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema (DME). DESIGN: Prospective, comparative interventional case series. METHODS: Twenty-eight eyes of 14 patients with bilateral DME participated in this study. In each patient, one eye received an intravitreal injection of 4 mg triamcinolone acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of best-corrected visual acuity (VA) with a logarithm of the minimum angle of resolution chart and averaged foveal thickness using optical coherence tomography was monitored for up to 24 weeks after the injection. RESULTS: Before the injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28 microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/- 0.18 microm in the bevacizumab-injected eye, respectively; there was no significant difference between the eyes. One week after the injection, both eyes showed significant regression of macular edema. The triamcinolone-injected eye (342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/- 0.17 microm). However, both eyes showed the recurrence of macular edema with time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25 microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/- 0.17 microm). CONCLUSIONS: With the generally used concentration, intravitreal injection of triamcinolone acetonide showed better results in reducing DME and in the improvement of VA than that of bevacizumab, suggesting that the pathogenesis of DME is not only attributable to VEGF-dependency, but is also attributable to other mechanisms suppressed by corticosteroid.

Okubo A, Hirakawa M, Ito M, Sameshima M, Sakamoto T. · Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17917739 No free full text.

Abstract: BACKGROUND: The pathogenesis of polypoidal choroidal vasculopathy (PCV), and even its clinical features, are controversial. Previous histopathological studies have identified different features; either dilated choroidal vessels or intra-Bruch's neovascularization. These differences might be partly attributable to the influence of the disease stage. We therefore evaluated the clinical features of early and late stage PCV. METHODS: The medical records of 110 eyes of 97 PCV patients were retrospectively reviewed. The time between the subjective onset of visual abnormality and examination at our clinic and the greatest linear dimension of the total lesion at the first examination were investigated. The period of disturbed vision and lesion size data were placed in ascending order to determine the first quartile point. Eyes with both values at or below the first quartile point were classified as 'small-short' (early stage). Eyes with both values equal to at least the third quartile point were classified as 'large-long' (late stage). Fundus photography, indocyanine green and fluorescein angiography, visual acuity, and clinical course were compared. RESULTS: Twelve eyes from 12 patients were small-short cases (period of disturbed vision of 1 month or less, lesion size 2.0 disc diameters or less). Eleven eyes from ten patients were large-long cases (period of disturbed vision 36 months or more, lesion size at least 5.0 disc diameters). The large-long eyes were characterized by occult choroidal neovascular membrane or scar tissue secondary to exudative age-related macular degeneration. Noticeable in the small-short eyes were atrophic changes in the retinal pigment epithelium, choroidal vessel hyperpermeability and pulsation. The visual prognosis and clinical course were different between the groups. CONCLUSIONS: The difference of clinical features between the groups might reflect different disease stages, although not all of the features observed in the small-short group appeared to represent the early stages of those recorded in the large-long group. Thus, the variation in histopathologic features among previous reports might be partly attributable to differences in disease stage.

Shimonagano Y, Doi N, Noda Y, Uemura A, Sakamoto T. · Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan. · Jpn J Ophthalmol. · Pubmed #17660988 No free full text.

Abstract: PURPOSE: To evaluate the effects of intravitreous triamcinolone acetonide (TA) after pars plana vitrectomy (PPV) for diabetic macular edema (DME). METHODS: We studied a prospective interventional case series. TA was injected intravitreously after PPV in 28 eyes (PPV+TA group). Eyes with DME that met the same criteria and had been treated with PPV alone (29 eyes) were used as controls. The best-corrected visual acuity (VA) and foveal thickness determined by optical coherence tomography were followed up for over 12 months in both groups. Chronological changes of VA and foveal thickness between the groups were evaluated. RESULTS: In the PPV+TA group, VA had improved at 1 month, but worsened after 3 months. Improvement of foveal thickness was found until 3 months, but not after 6 months. In controls, both VA and foveal thickness continued to improve. The VA of the PPV+TA group was significantly better than that of the controls at 1 and 3 months (P = 0.007 and 0.015, respectively). The foveal thickness of the PPV+TA group was significantly less than that of controls at 1 month (P = 0.0004). These differences became insignificant thereafter, and foveal thickness became significantly worse in the PPV+TA group than in the controls at 12 months (P = 0.0002). CONCLUSION: Although adjunctive use of TA after PPV for DME improved VA and foveal thickness, the effect was transient and foveal thickness increased significantly compared with the PPV alone group at 12 months postoperatively.

Shimonagano Y, Makiuchi R, Miyazaki M, Doi N, Uemura A, Sakamoto T. · Department of Ophthalmology, Faculty of Medicine, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan. · Jpn J Ophthalmol. · Pubmed #17554483 No free full text.

Abstract: PURPOSE: To report results of an investigation of visual acuity (VA) and foveal thickness in diabetic macular edema (DME) patients after vitrectomy. METHODS: A retrospective study was performed of the records of 47 patients (61 eyes) who received pars plana vitrectomy (PPV) for DME. All eyes were followed up for over 6 months (mean, 24.8 months; range, 6-60 months). VA and foveal thickness evaluated by optical coherence tomography were reviewed preoperatively and postoperatively. RESULTS: Twenty-four-month follow-up data were available for 46 of the 61 eyes (75%). VA at the final examination had improved by 0.2 log units or more in 34 of the 61 eyes (56%), remained unchanged in 21 eyes (34%), and worsened in six eyes (10%). Mean foveal thickness decreased by more than 20% of the preoperative value in 50 of the 61 eyes (82%), remained unchanged in ten eyes (16%), and increased by more than 20% in one eye (2%) at the final examination. Postoperative best-corrected visual acuity (BCVA) at both 12 and 24 months was significantly better than preoperative BCVA (P < 0.0001). Foveal thickness at 3 months or later significantly decreased from the preoperative value (P < 0.0001), but remained unchanged in comparison with postoperative 12 months and 24 months values (P = 0.19). Preoperative VA and presence of cystoid macular edema (CME) were independently associated with final visual acuity (P = 0.001). CONCLUSIONS: PPV for DME effectively improved VA and reduced foveal thickness for a longer postoperative period. Better preoperative VA was associated with better final postoperative VA. The eyes without CME tended to have better final postoperative VA.

Yamashita T, Uemura A, Kita H, Sakamoto T. · Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima, Japan. · J Glaucoma. · Pubmed #17473734 No free full text.

Abstract: PURPOSE: To evaluate long-term intraocular pressure (IOP) response after intravitreal injections of different doses of triamcinolone acetonide (TA) upon completion of pars plana vitrectomy (PPV) for macular edema secondary to diabetic retinopathy or retinal vein occlusion. PATIENTS AND METHODS: Retrospective, consecutive, comparative, interventional case series. Twenty-seven eyes of 25 consecutive patients with macular edema associated with diabetic retinopathy (n=18) or retinal vein occlusion (n=9), who underwent PPV for the treatment of macular edema between January 2003 and December 2003, were included. Upon completion of vitrectomy, different doses of TA were injected into the vitreous cavity: 14 eyes with 5 mg of TA (group 1) and 13 eyes with 10 mg of TA (group 2). The main outcome measure was IOP. RESULTS: All patients were followed up for at least 12 months. Preoperative IOP was 12.6+/-2.6 mm Hg (mean+/-standard deviation) in group 1 and 13.2+/-2.1 mm Hg in group 2. Postoperatively, IOP increased to a mean maximum of 20.6+/-5.5 mm Hg in group 1 and 31.5+/-3.5 mm Hg in group 2 (P<0.01 for both groups). The difference between groups was also significant (P<0.05). Five of 14 eyes (36%) in group 1 and 10 of 13 eyes (77%) in group 2 had an elevation of IOP exceeding 21 mm Hg (P=0.03). The median interval from surgery to reach maximal IOP was 7 days in both groups. The significant IOP elevation lasted for 3 months in group 1 and 6 months in group 2. CONCLUSIONS: After injecting of TA into the vitreous cavity upon completion of PPV for macular edema, a dose-dependent IOP elevation was observed, starting from early postoperative days and returning to normal values after several months. These results show that intravitreal TA injection in the vitrectomized eyes might have different IOP changes from in the nonvitrectomized eyes.

Matsumoto H, Yamanaka I, Hisatomi T, Enaida H, Ueno A, Hata Y, Sakamoto T, Ogino N, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Retina. · Pubmed #17290199 No free full text.

Abstract: OBJECTIVE: To determine whether triamcinolone acetonide (TA) can facilitate residual posterior vitreous hyaloid removal in pars plana vitrectomy (PPV), we examined the ultrastructure of inner limiting membrane (ILM) removed in TA-assisted PPV for diabetic macular edema (DME). PATIENTS AND METHODS: In this retrospective series of 38 eyes of 37 patients who underwent PPV and ILM removal for diffuse DME with posterior hyaloid attachment, 24 eyes underwent standard PPV without TA (control group), and 14 eyes underwent TA-assisted PPV (TA group). Excised ILMs during PPV were examined by transmission electron microscopy (control group, n = 20; TA group, n = 10) or scanning electron microscopy (control group, n = 4; TA group, n = 4). RESULTS: Transmission electron microscopy clearly demonstrated that the ratio of the posterior vitreous hyaloid remaining on ILM was significantly lower (P = 0.0187) in the TA group than in the control group and also that TA-assisted PPV successfully removed posterior hyaloid in five of seven eyes with TA granules remaining on the retinal surface even after surgical separation of the posterior vitreous. Scanning electron microscopy enabled spatial analysis of the residual posterior hyaloid on ILM, which appeared in a patchy fashion in the control group. CONCLUSIONS: TA-assisted PPV clearly demonstrated the residual posterior hyaloid on ILM and allowed more efficient removal of the posterior hyaloid than standard PPV.

Ito M, Okubo A, Sonoda Y, Yamakiri K, Sakamoto T. · Department of Ophthalmology, Faculty of Medicine, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan. · Ophthalmologica. · Pubmed #16491035 No free full text.

Abstract: AIM: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. METHODS: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. RESULTS: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. CONCLUSIONS: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.

Mochizuki Y, Hata Y, Enaida H, Yoshiyama K, Miyazaki M, Ueno A, Murata T, Sakamoto T, Kubota T, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. · Retina. · Pubmed #16467668 No free full text.

Abstract: PURPOSE: To evaluate the long-term outcomes of adjunctive surgical procedures during pars plana vitrectomy (PPV) for the treatment of diabetic macular edema (DME). METHODS: In this nonrandomized study, we retrospectively analyzed 57 eyes of 54 patients who had DME and had undergone PPV. We performed PPV using three different surgical procedures: conventional PPV (group PVD; 13 eyes), triamcinolone acetonide (TA)-assisted PPV (group TA; 22 eyes), and TA-assisted PPV combined with internal limiting membrane (ILM) peeling (group ILM; 22 eyes). We also evaluated the preoperative and postoperative best-corrected visual acuity (BCVA) results. RESULTS: The overall mean preoperative BCVA was 0.86 logarithm of the minimal angle of resolution unit. In groups PVD, TA, and ILM, BCVAs were 0.99, 0.90, and 0.74 (P = 0.310), respectively. The mean postoperative BCVA for all patients improved to 0.68 (P = 0.005). The postoperative BCVA improved in 47% of the treated eyes, it remained unchanged in 37% of the treated eyes, and it deteriorated in 16% of the treated eyes. However, we observed no significant difference in the mean postoperative BCVAs between the three groups. Furthermore, we found that there was no significant difference in postoperative BCVA improvements between any of the groups (P = 0.450). CONCLUSION: The present study suggests that these 3 PPV approaches do not significantly affect postoperative BCVAs after 18 months of DME treatment.

Doi N, Uemura A, Nakao K, Sakamoto T. · Department of Ophthalmology, Faculty of Medicine, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan. · Retina. · Pubmed #16141862 No free full text.

Abstract: PURPOSE: To study the vitreomacular adhesion and the contractile force of posterior hyaloid, which are shown in triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV). DESIGN: Interventional case series. METHODS: Twenty-eight eyes with diabetic macular edema (DME) without posterior vitreous detachment (PVD) received TA-assisted PPV. Surgical PVD was performed by an aspiration of vitrectomy probe, and the dynamic changes of posterior vitreous cortex and residual vitreous cortex were evaluated. RESULTS: A premacular defect was formed in the detached posterior vitreous cortex during surgical PVD in 27 of 28 eyes. Immediately thereafter, the small defect expanded into a large hole in the detached posterior vitreous cortex in all cases. A residual vitreous cortex was left on the macula in 22 eyes. CONCLUSIONS: These observations demonstrate a firm vitreoretinal adhesion in the central macula and suggest that the enlargement of the defect of posterior vitreous cortex may be extrusion of vitreous out through the premacular dehiscence into the preretinal space, or a tangentially contractile force may exist in the posterior vitreous cortex. Both macular adhesion and the traction of vitreous cortex might contribute to the pathogenesis of DME and other vitreomacular disease.

Sonoda KH, Sakamoto T, Enaida H, Miyazaki M, Noda Y, Nakamura T, Ueno A, Yokoyama M, Kubota T, Ishibashi T. · Department of Ophthalmology, Faculty of Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan. · Ophthalmology. · Pubmed #15019367 No free full text.

Abstract: OBJECTIVE: To visualize the residual vitreous cortex (VC) on the retinal surface after surgical posterior vitreous separation (PVS) during a pars plana vitrectomy (PPV), especially in patients with diabetic retinopathy. DESIGN: Case-control study. PARTICIPANTS: Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and rhegmatogenous retinal detachment (RRD). METHODS: A triamcinolone acetonide (TA)-assisted vitrectomy was performed on patients with the following diseases: PDR (40 eyes), DME (26 eyes), BRVO (11 eyes), and RRD (17 eyes). Eyes with no apparent preoperative posterior vitreous detachment were enrolled in this study. After performance of surgical PVS, the residual VC was visualized as a white gel highlighted by TA. Based on this finding, the residual VC pattern was then divided into 3 groups: (1) diffuse type (VC was diffusely present in the temporal vascular arcade), (2) focal type (a small island of VC was left), and (3) no residual VC. A multivariate analysis using analysis of variance was performed regarding the residual VC pattern, disease type, age, and the 3 different surgeons. MAIN OUTCOME MEASURES: Each surgeon determined the type of residual VC during the operation, and the results were confirmed by a postoperative review of the videotape records judged by the other 2 surgeons. RESULTS: Eighty percent of the PDR eyes demonstrated the diffuse type; 10%, the focal type; and 10%, no residual VC. Fifty-eight percent of the eyes with DME demonstrated the diffuse type; 19%, the focal type; and 23%, no residual VC. Eighteen percent of the BRVO eyes showed the diffuse type; 24%, the focal type; and 59%, no residual VC. Thirty percent of the RRD eyes showed the diffuse type; 30%, the focal type; and 40%, no residual VC. A multivariate logistic regression analysis showed that PDR was a predictor of the diffuse type of residual VC in comparison to RRD (odds ratio = 8.42, 95% confidence interval = 2.07-34.3). Neither age nor the surgeon was a significant factor for a specific type of residual VC. CONCLUSIONS: Diabetic eyes more often demonstrated the diffuse type of residual VC, even after surgical PVS. This information may be valuable for surgeons performing a PPV on patients with diabetic retinopathy.

Takeda A, Hata Y, Shiose S, Sassa Y, Honda M, Fujisawa K, Sakamoto T, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #12937991 No free full text.

Abstract: BACKGROUND: We investigated the role of the VEGF-VEGF receptor 2 (KDR) system in the development of choroidal neovascularization (CNV) and its possibility as a therapeutic target utilizing KDR selective receptor tyrosine kinase (RTK) inhibitor (SU5416) both in vitro and in an experimental CNV model. METHODS: VEGF-induced phosphorylation of KDR and p44/p42 MAPK in cultured bovine choroidal endothelial cells (BCECs) was determined by Western blot analysis. The proliferation and in vitro tube formation were analyzed by [3H]thymidine uptake and three-dimensional collagen gel model. For experimental CNV model, intense fundus laser photocoagulation was performed on pigmented rats. The anti-angiogenic efficacy of intraperitoneally injected SU5416 on experimental CNV was evaluated by fluorescein angiography and histology. The extent of fluorescein leakage on late-phase angiograms was scored, and the thickness of CNV membrane was histologically measured under a light microscope. RESULTS: VEGF-induced KDR phosphorylation in cultured BCECs was inhibited by SU5416 in a dose-dependent manner (0-3 microM) with IC50 of 0.29 +/- 0.071 microM. SU5416 treatment also resulted in a dose-dependent prohibition of VEGF-induced p44/p42 MAPK phosphorylation, [3H]thymidine uptake and in vitro tube formation with corresponding concentrations that inhibited KDR phosphorylation. The leakage score on fluorescein angiography for experimental CNV was significantly lower in the SU5416-treated group than in the control group (P<0.01). Histologically, the CNV membranes in the SU5416-treated group were 31.6% thinner than those in the control group (P<0.01). CONCLUSION: These results strengthen the evidence for a critical role of the VEGF-KDR system in the development of CNV, indicating that KDR selective inhibitor might be beneficial for the treatment of intraocular angiogenic diseases, including age-related macular degeneration.

Tsutsumi C, Sonoda KH, Egashira K, Qiao H, Hisatomi T, Nakao S, Ishibashi M, Charo IF, Sakamoto T, Murata T, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · J Leukoc Biol. · Pubmed #12832439 links to  free full text

Abstract: Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.

Yoshida M, Yoshida A, Honda K, Honda T, Sakamoto T, Ishibashi T. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #11031817 No free full text.

Abstract: BACKGROUND: The pathogenesis of age-related macular degeneration remains unknown. Environmental and genetic factors have been shown to be associated with in this disease. We report siblings with age-related macular degeneration. CASES: The proband (the third of 6 siblings) was found to have retinal pigment epithelial abnormalities and drusen of the right macula, and serous retinal detachment, drusen, and choroidal neovascularization of the left macula. Examination of the eldest siblings showed choroidal neovascularization, subretinal hemorrhage, and serous retinal detachment of the right macula. The left eye of the proband and the right eye of the eldest siblings were treated with laser photocoagulation. The fourth sibling was examined, and findings included retinal pigment epithelial abnormalities of both maculas and drusen of the right eye. The sixth sibling had drusen of the left macula. CONCLUSION: We report a family in which two siblings had age-related macular degeneration and two other siblings had abnormalities of the maculas.

Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H. · Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. · Gene Ther. · Pubmed #10849558 links to  free full text

Abstract: Accumulating evidence has shown the importance of vascular endothelial growth factor (VEGF) in chorioretinal angiogenesis. However, whether or not VEGF is indeed critical for the pathogenesis of subretinal neovascularization (SRN) in adulthood, which is a serious complication of age-related macular degeneration, has to be further investigated. We constructed an adenovirus expressing an entire ectodomain of the human VEGF receptor/flt-1 fused to Fc portion of human IgG (Adflt-ExR): this soluble receptor is secreted from Adflt-ExR-transfected cells. We studied the effect of Adflt-ExR on the formation of experimental SRN. Experimental SRN was induced by intense photocoagulation on the retina in pigmented rats and Adflt-ExR was injected into the femoral muscle. The formation of SRN assessed by fluorescein angiography was more significantly inhibited for 7 days in the Adflt-ExR-treated rats than in the control rats who received either an adenovirus vector encoding LacZ gene or balanced salt solution (BSS). The serum concentration of this soluble receptor increased for 7 days and thereafter gradually decreased. An immunohistochemical study disclosed the fibroblast cell proliferation and inflammatory cell infiltration to be reduced in the photocoagulation spot of Adflt-ExR-treated rats. VEGF plays a crucial role in the formation of SRN and VEGF soluble receptor gene transfection can inhibit SRN. This method will contribute to future gene therapy for age-related macular degeneration.

Kimura H, Spee C, Sakamoto T, Hinton DR, Ogura Y, Tabata Y, Ikada Y, Ryan SJ. · Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #9950614 links to  free full text

Abstract: PURPOSE: To determine the sequence of cellular changes associated with a new rabbit model of subretinal neovascularization (SRN) induced by subretinal injection of basic fibroblast growth factor (bFGF)-impregnated microspheres. METHODS: bFGF-impregnated gelatin microspheres, prepared by forming a polyion complex between gelatin and bFGF, were subretinally implanted into rabbit eyes. The eyes were studied by immunochemistry at 3 days to 8 weeks after implantation. Antibodies to CD4, CD8, cytokeratin, CD31, glial fibrillary acidic protein (GFAP), and RAM11 were used. RESULTS: Cytokeratin-positive retinal pigment epithelial (RPE) cells appeared on day 3 and continued to increase in number in the subretinal space throughout the growth of the SRN membrane, becoming the predominant cell type. Macrophages (RAM11-positive) appeared early, but most disappeared within 7 days. GFAP-positive Müller cells were evident early in the retina but migrated into the subretinal space after 7 days; the gliotic adhesion they formed between the retina and the SRN membrane was prominent at 8 weeks. CD31-positive endothelial cells were first evident at 14 days and formed neovascular channels that were still present for up to 8 weeks. CD4- and CD8-positive lymphocytes appeared in the early stages but were few in number. CONCLUSIONS: SRN membranes are primarily composed of RPE cells and vascular endothelial cells. The membrane adheres to the retina by a gliotic band. The cellular components involved in the membrane of this model resemble those found in SRN membranes removed from patients with age-related macular degeneration.