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Biomedical subjects

Hum Chung

Publications and source records attributed to Hum Chung.

At least 19 recordsLinked to original sources

Factors influencing refractive outcomes after combined phacoemulsification and pars plana vitrectomy: results of a prospective study.

PURPOSE: To evaluate the factors influencing the refractive outcomes of combined phacoemulsification, foldable intraocular lens (IOL) implantation, and pars plana vitrectomy (PPV). SETTING: Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. METHODS: One hundred fifty-four consecutive patients who had combined phacoemulsification, IOL implantation, and PPV between September 2001 and August 2004 were enrolled in a prospective study. Refractive, keratometric, and axial length measurements were performed preoperatively and 4 months postoperatively. The factors influencing the postoperative refractive outcomes were analyzed. RESULTS: The mean refractive prediction error (ie, actual minus predicted spherical equivalent [SE]) was -0.06 diopters (D) +/- 0.75 (SD). In long eyes (preoperative axial length more than 24.5 mm), the mean predicted SE and actual SE were -0.81 +/- 0.76 D and -1.24 +/- 0.79 D, respectively; the difference was significantly different (P = .001, paired t test). Patients with a preoperative visual acuity worse than 5/200 and those with preoperative foveal detachment had a significant postoperative myopic shift (P = 0.024 and P = 0.002, respectively; paired t test). Postoperative refractive error was not influenced by the intraocular air or gas tamponade during surgery (P = 0.336, paired t test). CONCLUSIONS: The combined surgery included a small biometric error that was within the tolerable range in most cases. However, myopic shifts developed in patients with long axial lengths, poor preoperative visual acuity, and the preoperative presence of foveal detachment.

Adult↗

Intraocular cytokine environment in active Behçet uveitis.

PURPOSE: To determine cytokine profiles in aqueous humor and peripheral blood from patients with Behçet uveitis. DESIGN: Prospective, experimental, and case-control study. METHODS: Aqueous humor and peripheral blood samples from 24 patients with Behçet uveitis, 28 patients with other causes of endogenous uveitis, and 20 healthy subjects after uncomplicated cataract surgery were obtained. Cytokines (interferon gamma (IFN-gamma), interleukin [IL]-2, IL-4, IL-10, IL-12, IL-15, and tumor necrosis factor alpha (TNF-alpha)) were measured by enzyme-linked immunosorbent assay and compared between the uveitis groups. RESULTS: Aqueous interferon gamma (IFN-gamma) levels were higher in patients with Behçet uveitis in contrast to higher concentrations of IL-4 in patients without Behçet uveitis. Aqueous levels of tumor necrosis factor alpha (TNF-alpha) were higher in patients with Behçet uveitis than in patients without Behçet uveitis. Aqueous and serum IL-10 were detected in all patients without Behçet uveitis, but were below detection limits in all patients with Behçet uveitis. Furthermore, IL-15 was exclusively increased in the aqueous humor of Behçet uveitis. The aqueous IL-2 or IL-12 levels were similar regardless of the presence of Behçet uveitis. CONCLUSIONS: Our results showed that an extreme Th1 polarization, a high proinflammatory condition, a low immunosuppressive status, and the presence of natural killer (NK) or CD8+ T cell-activating cytokine were unique features in aqueous humor with Behçet uveitis, suggesting that different immunopathogenic mechanisms may be involved in the ongoing intraocular inflammation of Behçet uveitis.

Adult↗

Combined low dose cyclosporine and prednisone down-regulate natural killer cell-like effector functions of CD8brightCD56+ T cells in patients with active Behçet uveitis.

PURPOSE: To investigate the changes of effector-related phenotypic markers and the natural killer (NK)-like effector functions of CD8(bright)CD56+ T cells in patients with Behçet uveitis after combined cyclosporine and prednisone (Cs/Pd) treatment. METHODS: Ten patients with active Behçet panuveitis and 10 healthy controls were prospectively recruited in this study. The effector-related surface markers (CD27, CD62L, CD11b, HLA-DR, CD94, NKG2D), chemokine receptors (CXCR1, CXCR3, CCR4, CCR5), and intracellular perforin of circulating CD8(bright)CD56+ T cells were determined by flow cytometric analysis before and after two months' treatment. NK-like cytotoxicity of ex vivo CD8(bright)CD56+ T cells against K562 was measured by standard 51Cr release assay. RESULTS: The expression levels of effector-related molecules on CD8(bright)CD56+ T cells normalized after treatment. The expression levels of CXCR1 and CCR5 were down-regulated on CD8(bright)CD56+ T cells after treatment. The amounts of preformed intracellular perforin of CD8(bright)CD56+ T cells were reduced to the normal levels. Furthermore, the NK-like cytolytic capacities of CD8(bright)CD56+ T cells were decreased after treatment. CONCLUSIONS: Our results suggest that the combined Cs/Pd treatments in active Behçet uveitis may downregulate the NK-like effector functions of CD8(bright)CD56+ T cells.

Adult↗

CD8brightCD56+ T cells are cytotoxic effectors in patients with active Behcet's uveitis.

Behçet's uveitis, characterized by chronic recurrent uveitis and obliterating retinal vasculitis, frequently causes bilateral blindness. Intraocular infiltration of TCRalphabeta+CD8brightCD56+ cells was a distinct feature in Behçet's uveitis. However, phenotypic natures and effector functions of the cells have remained elusive. This study was conducted to determine phenotypic and functional characteristics and cytotoxic mechanisms of CD8brightCD56+ T cells in Behçet's uveitis. CD11b+CD27-CD62L- phenotypes of CD8brightCD56+ T cells were increased in patients with active Behçet's uveitis compared with inactive Behcet's patients and normal controls. Interestingly, CD45RAdimCD45RO- phenotypes were expanded, and CD94 expression was markedly up-regulated in contrast to the down-regulation of NKG2D. Furthermore, these subsets were polarized to produce IFN-gamma and contained high amounts of preformed intracellular perforin while exclusively expressing surface FasL upon PI stimulation. Moreover, the cytolytic functions of freshly isolated CD8brightCD56+ T cells were up-regulated against both K562 (NK-sensitive) and Raji (NK-resistant) cells, which were effectively inhibited by perforin inhibitor (concanamycin A). Their cytolytic activity against HUVECs was also increased and was effectively suppressed by Fas ligand inhibitor (brefeldin A) and partly by perforin inhibitor. Furthermore, cytolytic functions of PMA and ionomycin-stimulated CD8brightCD56+ T cells against HUVECs were greatly enhanced, by pretreatment of recombinant human IFN-gamma on HUVECs. Therefore, CD8brightCD56+ T cells in Behçet's uveitis are characterized by cytotoxic effector phenotypes with functional NK receptors and function as strong cytotoxic effectors through both Fas ligand-dependent and perforin-dependent pathways.

Adult↗

Anatomical and functional characteristics in atrophic maculopathy associated with spinocerebellar ataxia type 7.

PURPOSE: To assess the anatomic and functional characteristics in a Korean family with spinocerebellar ataxia type 7-associated atrophic maculopathy. DESIGN: Observational case report. METHODS: Three patients in a family underwent funduscopic examination, fluorescein angiogram, full-field electroretinogram (ERG), electro-oculogram, and optical coherence tomography (OCT). Macular functions were assessed using multifocal ERG and scanning laser ophthalmoscope (SLO) microperimetry. RESULTS: Both eyes showed bull's eye configuration and cone-rod dystrophy phenotype. OCT revealed that retinal thinning extended outside the visibly atrophic lesions. Multifocal ERG demonstrated that amplitudes from the six ring segments were reduced in a centrifugal pattern. SLO microperimetry showed that fixations were unstable and shifted superior to the atrophic lesions. The areas of functional deficits were greater than those of anatomic deficits. CONCLUSIONS: Macular functions were severely depressed in atrophic maculopathy associated with spinocerebellar ataxia type 7 in both the visibly atrophic areas and the areas without visible atrophy in a centrifugal pattern.

Adult↗

Vitrectomy for persistent panuveitis in Behçet's disease.

PURPOSE: To determine whether vitrectomy is safe and effective for the management of vitreoretinal complications in Behçet's patients with persistent panuveitis. METHODS: Patients who had undergone therapeutic vitrectomy for Behçet's panuveitis were reviewed retrospectively. Those patients who had shown persistent uveitis despite maximum medical therapy were included. Surgical outcomes were measured by an improvement in vision of 0.3 logarithm of minimum angle of resolution, acute relapse rates, and postoperative complications. RESULTS: Twenty-one patients with a mean postoperative follow-up of 30 months were identified. For almost all patients visual acuity and inflammatory control were significantly improved after vitrectomy. However, patients with optic disc neovascularization (NVD) showed no improvement in their vision or inflammatory control. The postoperative rise of intraocular pressure was frequently associated with intravitreal triamcinolone acetonide injections. CONCLUSIONS: Our study suggests that vitrectomy may be both safe and effective for the management of vitreoretinal complications in Behçet's patients with persistent uveitis. Patients with NVD, however, may have poor outcomes.

Adult↗

Down-regulation of IFN-gamma-producing CD56+ T cells after combined low-dose cyclosporine/prednisone treatment in patients with Behçet's uveitis.

PURPOSE: To investigate the effects of combined low-dose cyclosporine and prednisone (Cs/Pd) treatment on circulating CD56+ T cells in patients with Behçet's uveitis. METHODS: Ten patients with Behçet's uveitis and 10 healthy control subjects were prospectively recruited. The patients were treated with Cs/Pd for 2 months. Phenotypic and functional changes in circulating CD56+ T cells were assayed before and after treatment. CD56+ T-cell subsets were determined by flow cytometric analysis with monoclonal antibodies for CD3, CD4, CD8, CD56, pan gammadelta TCR, and Valpha24. The absolute numbers of cells in the lymphocyte subsets were calculated. Cytokine (IFN-gamma, IL-4, and IL-10) expressions were measured by ELISA and by intracellular cytokine staining. RESULTS: The proportions of CD56+ T cells, specifically CD8highCD56+ and CD56+gammadelta T-cell subsets, were significantly higher in active Behçet's uveitis but normalized after treatment, whereas the total T-lymphocyte count and the absolute numbers of CD56- T cells were unaffected by treatment. The levels of IFN-gamma and IL-4 were elevated in aqueous humor and serum in Behçet's uveitis (P < 0.001), whereas IL-10 was not detected. After treatment, serum IL-4 levels markedly increased (P < 0.001), and IFN-gamma production by circulating CD56+ T cells was then suppressed. IL-4 and -10 production by CD56+ T cells was increased by treatment, but in contrast, minimal changes were found in CD56- T cells. CONCLUSIONS: The results imply that Cs/Pd treatment for Behçet's uveitis selectively affects the population of and the cytokine expression in CD56+ T cells, but without significant changes in CD56- T cells, and that IFN-gamma-producing CD56+ T cells are the central pathogenic immune cells in Behçet's uveitis.

Adult↗

Phacoemulsification and foldable intraocular lens implantation combined with vitrectomy and silicone oil tamponade for severe proliferative diabetic retinopathy.

PURPOSE: To determine the clinical outcomes of phacoemulsification and foldable intraocular lens (IOL) implantation combined with primary vitrectomy and silicone oil tamponade to treat severe proliferative diabetic retinopathy (PDR). SETTING: Department of Ophthalmology, Seoul National University College of Medicine, and Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea. METHODS: The results of combined cataract surgery and silicone oil injection in 20 eyes (20 patients) were retrospectively analyzed. All patients had tractional or tractional-rhegmatogenous retinal detachment and clinically significant lens opacities; none had previous intraocular surgery. An acrylic foldable IOL was implanted in the capsular bag or ciliary sulcus. RESULTS: Primary anatomic success was achieved in 90% of eyes. Functional success was attained in 60% of eyes after a mean follow-up of 7.6 months. The postoperative visual acuity improved in 60% of patients, was unchanged in 20%, and was worse in 20%. Silicone oil was removed in 80% of patients without complications after a mean of 3.4 months. The mean absolute value of the difference between the predicted refraction and postoperative refraction was 0.74 diopter (D) (range 0.03 to 1.74 D). CONCLUSION: Phacoemulsification and foldable IOL implantation combined with primary vitrectomy and silicone oil tamponade was performed safely with favorable anatomic and visual outcomes in eyes with severe PDR.

Adult↗

Retinal detachment of regressed retinopathy of prematurity in children aged 2 to 15 years.

PURPOSE: To reveal the clinical features and surgical results of retinal detachment of regressed retinopathy of prematurity (ROP) that occur in the children aged 2 to 15 years. PATIENTS AND METHODS: The records of patient who had a retinal detachment of a regressed ROP were retrospectively reviewed. Sixteen eyes from 15 patients that required surgical treatments due to retinal detachment of a regressed ROP were included. RESULTS: After treatment of acute phase of ROP, eight eyes showed grade II of cicatricial change and eight eyes showed grade III. We did not find any evidence that the acute stages of ROP and its treatment affect the degree of the cicatricial changes. All eight eyes with grade III of cicatricial ROP showed tractional retinal detachment (TRD) and five of eight eyes (62.5%) with grade II showed rhegmatogenous retinal detachment (RRD). The mean interval between regressed ROP and development of late retinal detachment was 20.7 months (range, 12-61 months) in the TRD group and 85.8 months (range, 33-148) in the RRD group. The mean age at onset of late detachment was 34.1 months (range, 26-73 months) in the TRD group and 98.6 months (range, 45-162) in the RRD group. Anatomical success was achieved at one of five eyes (20%) with RRD and six of 11 eyes (54.5%) with TRD. Compared with the preoperative visual acuity, visual improvement, no change, and decreased visual acuity were achieved, respectively, in two eyes, three eyes, and no eyes in the RRD group and three eyes, six eyes, and two eyes in the TRD group. However, only two of 16 eyes with late retinal detachment achieved a visual acuity of 20/200 or better. CONCLUSION: Late retinal detachment is the main vision-threatening condition in patients with regressed ROP during childhood. The visual prognoses of these patients are poorer than those with late retinal detachments that occur in adult ROP patients. Therefore, a periodic fundus examination should be performed more frequently during childhood than in adulthood, particularly in nonverbal children.

Acute Disease↗

Retinal pigment epithelial cell behavior is modulated by alterations in focal cell-substrate contacts.

PURPOSE: To investigate how the cellular behavior of cultured retinal pigment epithelial (RPE) cells was affected by the manipulation of early focal contact. METHODS: To manipulate early focal contact, a reduced focal cell-substrate contact area on the micropatterned surfaces was implemented by microfabrication with polydimethylsiloxane (PDMS). The micropatterned PDMS surfaces had a circular pillar with a diameter of 5 microm. The human retinal pigment epithelial cell line, ARPE-19, was seeded onto the fibronectin-coated PDMS surfaces. Cell adhesion, growth, cell cycle, morphology, and interleukin-6 (IL-6) expression were observed for 3 weeks. RESULTS: The fluorescent images of localized vinculin and actin stress fibers appeared to be more prominent on smooth PDMS surfaces. Although there was no significant effect on cell adhesion, a statistically significant inhibition of cell cycle progression was observed for micropatterned PDMS surfaces. Similarly, micropatterned surfaces showed significantly less cell growth than that of smooth surfaces. Cultures over a period of 3 weeks showed a distinct cell-cell phenotype discrepancy. Furthermore, IL-6 mRNA and secreted protein induced by IL-1beta in ARPE-19 were downregulated on micropatterned PDMS surfaces. CONCLUSIONS: Disturbed focal contact in ARPE-19 cells grown on micropatterned surfaces altered cell cycle, growth, morphology, and the expression of IL-6 in vitro.

Actins↗

Long-term effect of plasmin on the vitreolysis in rabbit eyes.

The aim was to investigate the proteolytic activity of plasmin and its long-term complications. Plasmin was injected into the vitreous cavity of rabbits' eyes. Slit lamp biomicroscopy and electroretinography were performed. Rabbits were serially sacrificed at four months, and globes fixated and prepared for light and transmission electron microscopy. In both the plasmin-injected and control eyes, electroretinography showed a transient decrease in the amplitude, but this recovered to the baseline level in a week. Under the light microscope, the plasmin-treated eyes had a smooth retinal surface, implying separation of the vitreous cortex from the retina. In the control eyes, the collagen fibers remained on the retinal surface. By transmission electron microscopy, the plasmin-treated eyes showed a vitreous-free retinal surface, but no vitreoretinal separation was observed in the control eyes. Plasmin induces a cleavage between the vitreous and the internal limiting membrane, with no long-term complications, so may be a useful pharmacologic adjunct to vitrectomy.

Animals↗

A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

AIDS-Related Opportunistic Infections↗

Stellate ganglion block increases blood flow into the optic nerve head and the peripapillary retina in human.

The effects of stellate ganglion block (SGB) on the blood flow of the optic nerve head (ONH) and the peripapillary retina, which plays an important role in the pathogenesis of a major blinding disease, e.g. glaucoma, are unclear. The aim of this study was to evaluate the effects of a sympathetic block on the blood flow of the ONH and the peripapillary retina. Heidelberg Retinal Flowmetry, which is a system incorporating a noninvasive confocal scanning laser Doppler flow meter, was used to measure the retinal blood flow. A unilateral stellate ganglion block was performed in 11 healthy subjects. The retinal blood flows were measured before, 30 and 120 min after SGB. On each occasion, three scans were obtained and the blood flow was analyzed. The systemic blood pressure (BP) and the intraocular pressure (IOP) were also measured at the set time points. The blood flow of the ONH and the peripapillary retina of the ipsilateral retina was significantly increased (P=0.001) by 106.8% and 98.7%, respectively, 30 min after SGB without accompanying significant changes in BP and IOP when compared to their baseline values; while those of the contralateral eyes did not change. The effect of SGB on blood flow in these areas disappeared 120 min after SGB. In conclusion, SGB may have a beneficial effect on ocular diseases associated with ischemia of the ONH and the peripapillary retina, e.g. glaucoma.

Adult↗

Transscleral fixation of a foldable intraocular lens in aphakic vitrectomized eyes.

PURPOSE: To evaluate the clinical outcomes of transscleral fixation of a foldable intraocular lens (IOL) in eyes that had pars plana lensectomy combined with pars plana vitrectomy for severe vitreoretinal disease. SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: The medical records of 21 patients who had a transscleral fixation of a foldable IOL after previous vitrectomy combined with lensectomy for severe posterior segment pathology were reviewed. The underlying vitreoretinal diseases were complicated proliferative diabetic retinopathy (n = 9), proliferative vitreoretinopathy (n = 5), traumatic retinal detachment (n = 3), intraocular foreign body (n = 2), and uveitic retinal detachment (n = 2). The postoperative best corrected visual acuity (BCVA) was compared with the preoperative BCVA. Autorefractometry and keratometry measurements and central endothelial cell counts were evaluated 1 day preoperatively and 6 months postoperatively. RESULTS: The mean age of the patients was 54.5 years. The preoperative aphakic period ranged from 2 to 22 months. The visual acuity reached the preoperative BCVA by 2 months after surgery and was better than the preoperative BCVA at 6 months (P =.006) and at the final visit (P =.003). Six months postoperatively, the mean myopic shift by cycloplegic autorefractometry was -1.0 diopter (D) and the mean scalar shift in surgically induced keratometric cylinder, 1.0 D. The mean central corneal endothelial loss at 6 months was 6.7% (range 2.4% to 22.2%). The only vitreoretinal complications were a transient vitreous hemorrhage and a reopened macular hole that was reattached after fluid-gas exchange. CONCLUSION: Transscleral fixation of a foldable IOL was safe and led to favorable visual outcomes in aphakic vitrectomized eyes with previous severe vitreoretinal disease.

Adult↗

A new rapid and non-radioactive assay for monitoring and determining the proliferation of retinal pigment epithelial cells.

AlamarBlue is used to induce color and fluorescence in the microenvironment of activated cells. The alamarBlue assay was studied to determine if it could be used as a method of evaluating the number of retinal pigment epithelial (RPE) cells. A series of two-fold dilutions of RPE cells were placed into 96-well culture plates. The alamarBlue was added to the culture media after attaching the cells. The absorbance and fluorescence were measured consecutively at various intervals over a period of 24 hr. Cell viability were evaluated by means of the trypan blue exclusion method and flow cytometry using a combination of propidium iodide and annexin V was done to prove the safety of alamarBlue assay to the cells. Both the absorbance and the fluorescence had a linear relationship with the number of RPE cells. Exposing the RPE cells to alamarBlue was not detrimental to the cells. In conclusion, the alamarBlue assay constitutes a one-step, extremely simple, reproducible, economical and non-toxic procedure for evaluating the number of viable RPE cells.

Cell Count↗

Effect of the absence of heat shock protein 70.1 (hsp70.1) on retinal photic injury.

This study aimed to evaluate the protective effect of heat shock protein70 (hsp70) on retinal photic injuries, and to determine the relationship between hsp70s from hsp70.1 and 70.3. C57BL/6 wild type (hsp70.1 +/+) and knockout type (hsp70.1 -/-) mice from the same littermates were placed in light of 11000 lux for 6 hours, and were sacrificed at 1, 4, 7, and 14 days after stress. H & E staining, immunohistochemistry, and western blot analysis were performed. The hsp70.1 -/- mice exhibited more disarranged and more diffusely destroyed photoreceptors than the hsp70.1 +/+ mice. Hsp70 induction by light in both the hsp70.1 +/+ and hsp70.1 -/- mice peaked at 1 day after light stress. The Hsp70 level in the hsp70.1 +/+ mice reduced slowly and was almost constant for 7 days. However, in the hsp70.1 -/- mice, it decreased rapidly and returned, after 7 days, to a similar level to that prior to light exposure. According to which gene they originate from, hsp70s may play specific roles in protecting the retina against stresses. Hsp70 from the hsp70.1 gene may act as a sustained responder to retinal photic injury.

Animals↗

Combined surgery and sequential surgery comprising phacoemulsification, pars plana vitrectomy, and intraocular lens implantation: comparison of clinical outcomes.

PURPOSE: To evaluate the effectiveness and safety of combined phacoemulsification, pars plana vitrectomy (PPV), and intraocular lens (IOL) implantation in diabetic and nondiabetic patients and compare the clinical results with those of sequential surgery. SETTING: Seoul National University College of Medicine, Seoul, South Korea. METHODS: The results of combined phacoemulsification, PPV, and IOL implantation in 52 patients (52 eyes) were retrospectively analyzed. The main outcome measures were preoperative and postoperative best corrected visual acuity (BCVA), postoperative BCVA of 20/40 or better, and intraoperative and postoperative complications. Combined surgery and sequential surgery were also compared using the same outcome measures. RESULTS: Postoperatively, the BCVA was better in 44 eyes (84.6%); 12 eyes (23.1%) achieved a BCVA of 20/40 or better. Postoperative complications consisted of a transient intraocular pressure increase in 29 eyes (55.8%), hyphema in 10 (19.2%), neovascular glaucoma in 8 (15.4%), anterior chamber fibrin exudation in 7 (13.5%), vitreous hemorrhage in 7 (13.5%), retinal detachment in 3 (5.8%), and posterior capsule opacification in 1 (1.9%). In the diabetic patients, postoperative visual outcomes between the combined-surgery group and the sequential-surgery group were not significantly different; however, neovascular glaucoma occurred only in the combined-surgery group. Other complications were not different between the combined-surgery group and the sequential-surgery group. In the nondiabetic patients, the postoperative visual outcomes and complications between the 2 groups were not significantly different. CONCLUSIONS: Combined phacoemulsification, PPV, and IOL implantation was safe and effective in selected patients, with the clinical outcomes comparable to those of sequential surgery.

Adult↗

Effect of 2'-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model.

PURPOSE: To investigate whether 2'-benzoyl-oxycinnamaldehyde (BCA) induces apoptosis in human retinal pigment epithelial (hRPE) cells and has an antiproliferative effect in a proliferative vitreoretinopathy (PVR) model in the rabbit. METHODS: Fifty percent growth inhibition doses of hRPE cells at 50%, 75%, and 100% confluence were determined by MTT assay. Apoptosis in hRPE cells induced by BCA was shown by DAPI staining. Expression of p53, p21, Bcl-2, GADD45, cyclin D, phospho-MAP kinase, cdk2, and Akt1 at various concentrations of BCA in cultured hRPE cells was examined by immunoblot analysis. In the efficacy study, 2.0 x 10(5) rabbit RPE cells were injected into the vitreous cavity after gas compression, and the eyes subsequently received either sham injections or 600 micro M BCA. Fundus examination was performed before and 1, 7, 14, 21, and 28 days after BCA injection. The toxicity studies were conducted by the same protocol as used for the efficacy evaluation but without the RPE cell injection. Simultaneous electroretinograms were recorded on days 1, 7, 14, 21, and 28 after exposure to the drug. RESULTS: BCA treatment induced apoptosis in hRPE cells. Furthermore, an increase in p53 expression, phosphorylation of Bcl-2, and downregulation of Akt1 expression were observed in BCA-induced apoptotic cells. BCA effectively prevented the proliferation of rabbit RPE cells in the experimental PVR model. BCA exhibited a wide safety margin, showing no evidence of causing retinal toxicity, even at the 600- micro M concentration. CONCLUSIONS: The results of this study suggest that BCA effectively inhibits proliferation of RPE cells and has a very wide safety margin, indicating a potential therapeutic usefulness in treating PVR.

Acrolein↗