Biomedical subjects

Jae Chan Kim

Publications and source records attributed to Jae Chan Kim.

18 recordsLinked to original sources

PubMed2006

Inhibition of corneal neovascularization by rapamycin.

The purpose of this study was to determine whether rapamycin could inhibit corneal angiogenesis induced by basic fibroblast growth factor (bFGF). Using human dermal microvascular endothelial cells (HDMECs), we examined the effect of rapamycin on cell proliferation and migration, and the expression of vascular endothelial growth factor (VEGF). The rabbit's eye was implanted intrastromally into the superior cornea with pellet containing bFGF for the control group and pellet containing bFGF and rapamycin for the rapamycin group. Biomicrographically, corneal angiogenesis was evaluated for 10 days after pellet implantation. The neovascularized cornea also was examined histologically. bFGF induced corneal neovascularization was significantly reduced by treatment with rapamycin. Using in vitro model, rapamycin strongly inhibited bFGF induced proliferation, migration, and VEGF secretion of HDMECs. We could observe that the bFGF induced corneal angiogenesis was inhibited by rapamycin in a micropocket rabbit model. The score of neovascularization was significantly decreased in the rapamycin group than in the control group at 10 days after pellet implantation. Histologically, the cornea of rapamycin group also showed much less new vessels than that of control group. Collectively, rapamycin appears to inhibit bFGF induced angiogenesis in a rabbit corneal micropocket assay and may have therapeutic potential as an antiangiogenic agent.

Angiogenesis Inhibitors↗

PubMed2006

Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation.

PURPOSE: To evaluate the changes in laser iridotomies, intraocular pressure (IOP), angle structures, and pupil diameter after implantable contact lens (ICL) (Version 4 Staar Surgical) implantation in myopic Asian eyes. SETTING: Department of Ophthalmology, Chung-Ang University Yongsan Hospital, Seoul, Korea. METHODS: The ICL was implanted in 81 eyes of 43 patients with spherical equivalent greater than -6.00 diopters. Gonioscopy examination was performed 1 day after laser iridotomy and 6 and 12 months after ICL implantation. The changes in laser iridotomy sites, IOP, and pupil diameter were also evaluated. RESULTS: Ten eyes (12.3%) had occlusion or narrowing of the laser iridotomy sites. The angle width was more than 30 degrees in all cases preoperatively but narrowed to less than 20 degrees in 16 eyes (19.8%) 6 months postoperatively. The mean pigment, measured by the semiquantitative method (grade 0 to 4), was 2.03 in the inferior angle, 0.18 in the nasal angle, 0.12 in the temporal angle, and 0.00 in the superior angle 12 months postoperatively. The pigment in all quadrants increased temporally as a result of the laser iridotomy or iris rubbing by the ICL; however, the pigments absorbed gradually and decreased to values before laser iridotomy 12 months postoperatively. There was a temporary increase in IOP from the instillation of steroid eyedrops 1 week and 1 month postoperatively; IOP returned to the preoperative level and remained there 12 months postoperatively. There was a significant decrease in pupil diameter 1 and 3 months postoperatively; the diameter returned to the preoperative size at 6 and 12 months. Pigment dispersion syndrome and pigmentary glaucoma were not seen. CONCLUSION: Implantation of the ICL narrowed the angle width but did not increase trabecular pigmentation compared with values after laser iridotomy, indicating ICL implantation is safe regardless of the pigmentary changes in the trabecular meshwork.

Adult↗

PubMed2006

Amniotic membrane corrects surgically induced astigmatism.

Human amniotic membrane (AM) has been widely used for the reconstruction of ocular surface. We conducted this study to investigate whether AM shows efficacy in maintaining the correction of astigmatism or not. We performed photoastigmatic refractive keratectomy (PARK) on rabbits and grafted AM on the cornea. The effect of AM on the degree of astigmatism was evaluated by topography and cycloplegic refraction. As will be shown, AM did not show any efficacy in maintaining the correction of astigmatism. On the contrary, AM not only eliminated PARK-induced astigmatism but prevented surgically induced astigmatism. We suggest that AM could be a useful tool for controlling the astigmatism induced by laser refractive surgery. Further clinical study is still left to be elucidated.

Amnion↗

PubMed2006

The changes in corneal astigmatism after botulinum toxin-a injection in patients with blepharospasm.

To determine if the involuntary contractions of eyelids may have any effects on the development of corneal astigmatism, we performed this prospective study which includes 19 patients with either essential blepharospasm or hemifacial spasm. In hemifacial spasm, the degree of corneal astigmatism was evaluated between two eyes. Then the topographic changes were checked using vector analysis technique before and after passively opening the eyelids. They were also measured before and at 1 and 6 months after the injection of Botulinum toxin. Resultantly, 20 eyes had the with-the-rule (group1) and 9 eyes against-the-rule (group2) astigmatism. In hemifacial spasm, significantly more astigmatism was found at spastic eyes. The corneal topographic changes after passively opening the eyelids showed 10 eyes with the astigmatic shift to the with-the-rule, while the remaining 19 to the against the- rule. At 1 month after injection of Botulinum toxin, group 1 showed reduced average corneal astigmatism, whereas group 2 showed increased astigmatism. The astigmatic change vector showed significantly more against-the-rule. In the contrary, 6 months after treatment, corneal astigmatism again increased in group 1 and decreased in group 2. So they took on the appearance of pretreatment astigmatic status eventually. Conclusively eyelids may play an important role in corneal curvature.

Aged↗

PubMed2006

A novel application of amniotic membrane in patients with bullous keratopathy.

To evaluate the efficacy of amniotic membrane in the management of painful bullous keratopathy secondary to the intractable glaucoma and in preventing exposure of drainage devices, we inserted Ahmed valve with amniotic membrane patch graft over the implant itself, and debrided corneal epithelium with amniotic membrane graft over the exposed stroma as a single operation. During the follow-up periods, we monitored vision, intraocular pressure (IOP), presence of ocular pain, and postoperative complications associated with the implants. The mean follow up period was 8.4+/-3.2 months. IOP was well controlled after the intervention. The preoperative mean IOP was measured as 43.9+/-9.0 mmHg and lowered to 16.1+/-1.8 mmHg at the last visit and no complications associated with the implants were noted. Even though the improvement in vision was not prominent, the ocular surface stabilized rapidly and ocular pain associated with bullous keratopathy disappeared soon after surgery. Conclusively the use of amniotic membrane in conjunction with Ahmed valve implantation is an effective way to relieve ocular pain and lessen the chances of complications associated with the implant in patients with intractable glaucoma and bullous keratopathy.

Aged↗

PubMed2006

Ultrastructural analysis of in vivo expanded corneal epithelium on amniotic membrane.

The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3+/-1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM.

Adult↗

PubMed2005

The involvement of adult stem cells originated from bone marrow in the pathogenesis of pterygia.

Pterygium is a proliferative disease. Recent research has reported that stem cells are involved in the pathogenesis of various proliferative diseases, including solid tumors and diabetic proliferate vitreoretinopathy. In previous literature, we hypothesized that adult stem cells originated from bone marrow were involved in the pathogenesis of pterygium. We proved this by immunohistochemical staining with various stem cell markers. The staining showed adult stem cells in the pterygium. c-kit positive cells were observed primarily in the stroma, and some cells were also found in the basal epithelium. AC133 and CD34 positive cells were primarily found in the basal epithelium and were ovoid shaped, similar to the c-kit cells. However, some cells were found in vascular endothelium. STRO-1 positive cells were found mainly in the stroma and were spindle shaped. In recurrent pterygium, cells were more scattered and the expression pattern was denser. Therefore, we suggest a new theory of pterygium pathogenesis. Inflammation caused by environmental factors triggers the abnormal production of some growth factors and cytokines in order to recover from cellular damage. If these healing signals are excessive, limbal basal cells will be changed to abnormally-altered pterygial cells. The excessive wound healing process and remnant altered cells result in recurrence using the same mechanism.

AC133 Antigen↗

PubMed2005

The involvement of multipotential progenitor cells in Mooren's ulcer.

The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and a-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

Cornea↗

PubMed2005

Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo.

PURPOSE: To examine the effect of rapamycin on the proliferation and the migration of human umbilical vein endothelial cells (HUVECs) and on the corneal neovascularization in the corneal alkaline burn murine model. METHODS: HUVEC proliferation, migration, and apoptosis were examined after treatment with rapamycin. The effect of rapamycin on the mRNA expression of FK506 binding protein (FKBP)-12 and mammalian target of rapamycin (mTOR) was also evaluated in vitro. Corneal neovascularization was induced in vivo by an alkaline burn of the cornea with 1 N NaOH on BALB/c mice. Rapamycin was given intraperitoneally at 2 mg/kg body weight once a day for 12 days after the corneal alkaline burn. Growth factors and cytokines related with neovascularization and inflammation were evaluated in the corneal tissue and the peripheral blood by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The corneal neovascularization was evaluated by a slit lamp biomicroscopy. RESULTS: Rapamycin at the concentration of 1000 ng/mL for >48 hours' exposure significantly inhibited the growth of HUVECs. The double chamber assay showed that rapamycin dramatically inhibited the migration of HUVECs at concentrations of 10 and 100 ng/mL and that these concentrations did not affect endothelial cell growth. When TUNEL assays were performed, the number of apoptotic cells increased 1.9-, 2.1-, and 2.6-fold compared with the control at 10, 100, and 1000 ng/mL, respectively, of rapamycin at 48 hours of exposure. RT-PCR showed that the expression of mTOR was suppressed in the HUVECs after rapamycin treatment; however, FKBP-12 expression was not affected. Among the angiogenic factors, gene expression of substance P and hypoxia inducible factor (HIF)-1 alpha was inhibited by rapamycin earlier (1-3 days), with vascular endothelial growth factor (VEGFR)-1 gene expression being suppressed for the first 7 days in the corneal tissue. The protein level of substance P and vascular endothelial growth factor (VEGF) was significantly decreased--more in mice treated with rapamycin than the control mice--as shown by ELISA assay of peripheral blood. Furthermore, rapamycin significantly inhibited corneal neovascularization in the alkaline-burned cornea. CONCLUSIONS: Rapamycin strongly inhibited HUVEC migration at doses that did not cause cytotoxicity and apoptosis in this in vitro model. Rapamycin also suppressed corneal neovascularization, possibly by inhibiting proinflammatory cytokines, as shown by the in vivo study. Therefore, rapamycin may be useful as an angiogenic regulator in the treatment of corneal diseases that manifest with neovascularization.

Animals↗

PubMed2004

Effect of thermal preconditioning before excimer laser photoablation.

The purposes of this study were to assess the expression patterns of heat shock proteins (Hsps), after eyeball heating or cooling, and to elucidate their relationships with corneal wound healing and intraocular complications after excimer laser treatment. Experimental mice were grouped into three according to local pretreatment type: heating, cooling, and control groups. The preconditioning was to apply saline eyedrops onto the cornea prior to photoablation. Following photoablation, we evaluated corneal wound healing, corneal opacity and lens opacity. Hsp expression patterns were elucidated with Western blot and immunohistochemical staining. The heating and cooling groups recovered more rapidly, and showed less corneal and lens opacity than the control group. In the heating and cooling groups, there were more expressions of Hsps in the cornea and lens than in the control group. These results were confirmed in the Hsp 70.1 knockout mouse model. Our study showed that Hsps were induced by the heating or cooling preconditioning, and appeared to be a major factor in protecting the cornea against serious thermal damage. Induced Hsps also seemed to play an important role in rapid wound healing, and decreased corneal and lens opacity after excimer laser ablation.

Animals↗

PubMed2004

New treatment for band keratopathy: superficial lamellar keratectomy, EDTA chelation and amniotic membrane transplantation.

We report two cases of band keratopathy who were treated with thick amniotic membrane that contained a basement membrane structure as a graft, after ethylenediaminetetraacetic acid chelation with trephination and blunt superficial lamellar keratectomy in the anterior stroma. In each case, basement membrane was destroyed and calcium plaque invaded into anterior stroma beneath Bowman's membrane. The calcified lesions were removed surgically, resulting in a smooth ocular surface, and the fine structures of band keratopathy were confirmed by pathologic findings. After that, amniotic membrane transplantation was performed to replace the excised epithelium and stroma. Wound healing was completed within 10 days. Stable ocular surface was restored without pain or inflammation. During the mean follow-up period of 13.5 months, no recurrence of band keratopathy was observed. This combined treatment is a safe and effective method for the removal of deep-situated calcium plaque and allowing the recovery of a stable ocular surface.

Amnion↗

PubMed2003

In vivo conjunctival reconstruction using modified PLGA grafts for decreased scar formation and contraction.

The in vivo reconstruction of conjunctiva was investigated by using modified poly(lactide-co-glycolide) (PLGA) 50/50 scaffolds. The porous PLGA matrices were prepared by a solvent-casting particulate-leaching method with NaCl, then modified with collagen, hyaluronic acid (HA) or/and human amniotic membrane (AM) component. The growth of corneal epithelial cells and human stromal fibroblasts on the scaffolds was investigated in vitro. All the modified PLGA scaffolds demonstrated enhanced cell adhesion and proliferation as compared to PLGA untreated, and the number of cells proliferated after 1 week was increased in the order of PLGA<PLGA/collagen=PLGA/collagen/AM<PLGA/collagen/HA=PLGA/collagen/AM/HA, which was the same order as the adhesion of the cells onto the surfaces. Conjunctival wounds were created on the eyes of white rabbits bilaterally and PLGA/collagen/HA scaffolds were grafted for 4 weeks to evaluate the regeneration of ocular surface tissue at the wounds. At postoperative 4 weeks, all the wounds were completely covered with epithelial membranes. However, the contraction was minimal (6%) in the wound grafted with the modified PLGA, while that of the ungrafted wound was substantially large (25%). In addition, the collagen fibers regenerated within the scaffolds were characterized by a random array of a loose network that resembled natural conjunctiva. On the contrary, an aligned array of dense collagen fibers formed in the ungrafted wounds. Our results indicated that the modified PLGA graft as an acellular bed might allow the reconstruction of the damaged conjunctival tissue with less scar formation and contraction.

Animals↗

PubMed2003

Repair of scleromalacia using preserved scleral graft with amniotic membrane transplantation.

PURPOSE: To evaluate the use of preserved scleral graft with amniotic membrane transplantation (AMT) for the surgical repair of scleromalacia. METHODS: A prospective study of eight eyes (eight patients) was performed. We grafted glycerin-preserved sclera onto the areas of scleral thinning with impending perforation and then covered them with an amniotic membrane with a thick basement membrane instead of a conjunctival flap. RESULTS: All patients experienced loss of ocular pain and inflammation, rapid reepithelialization of the ocular surface, and marked improvement in visual acuity. All of the scleral grafts remained intact, and no recurrence of scleromalacia was observed. CONCLUSION: Preserved scleral graft with AMT was simple, fast, and effective. It was particularly advantageous when large scleral defects or conjunctival scarring was present. With these therapeutic results, preserved scleral graft with AMT qualifies as a new treatment alternative for scleromalacia.

Aged↗

PubMed2003

Stepwise surgical approach for in vivo expansion of epithelial stem cells to treating severe acute chemical burns with total limbal deficiency.

To describe the clinical outcome of a new surgical treatment for the acute stages of severe corneal burn injury and its complications, a prospective study of five acute corneal burn patients with severe limbal damage was performed. Amniotic membrane transplantation (AMT) and conjunctival limbal autograft (CLAU) was performed at the acute stage of corneal burn injury to reconstruct the damaged ocular surface (step I). Three to six months later, the opaque central part of the amniotic membrane containing in vivo grown corneal stem cells were removed and retransplanted to the defect created after the removal of pseudopterygium (step II). All injured eyes were successfully treated, but in one eye with marked stromal lysis, three-layered AMT and penetrating keratoplasty with retransplantation of in vivo grown corneal stem cells was performed. In the former cases, visual acuity was greatly improved more than three lines (ranging from 3 to 12 lines). In short, retransplantation of in vivo grown corneal stem cells after AMT and CLAU is a recommendable modality for restoring a stable corneal epithelium of a severely burned ocular surface in the acute stage and can be considered a preventative measure for avoiding late onset complications.

Acute Disease↗

PubMed2002

Cleft lip and palate incidence among the live births in the Republic of Korea.

We present an epidemiologic study of cleft lip and palate in the Republic of Korea from January 1, 1993 through December 31, 1993. In 1993, the number of total live births was 715,817. And from 1993 through 1995, a total of 1,293 new patients with cleft lip and palate who were born in 1993 were identified. The incidence of cleft lip and palate was 1.81 per 1000, that is, 1 per 554 live births. The cleft lip: cleft lip and palate: cleft palate alone ratio was 1.13:1:1.19. The male: female ratio was 2.1:1 in the cleft lip group, and 2.5:1 in the cleft lip and palate group. We could detect a male predominance in both groups. In contrast, the ratio was 0.95:1 in the cleft palate group. The left: right: bilateral ratio was 1.9:1:0.23 in cleft lip group, and the ratio was 2.2:1:1.1 in the cleft lip and palate group. This is the first nation-wide study to provide detailed data on the incidence of cleft lip and palate in the live births in the Republic of Korea.

Cleft Lip↗

PubMed2002

The role of nitric oxide in ocular surface cells.

The role of nitric oxide (NO) in the ocular surface remains unknown. We investigated the conditions leading to an increase of NO generation in tear and the main sources of NO in ocular surface tissue. We evaluated the dual action (cell survival or cell death) of NO depending on its amount. We measured the concentration of nitrite plus nitrate in the tears of ocular surface diseases and examined the main source of nitric oxide synthase (NOS). When cultured human corneal fibroblast were treated with NO producing donor with or without serum, the viabilities of cells was studied. We found that the main sources of NO in ocular surface tissue were corneal epithelium, fibroblast, endothelium, and inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in experimentally induced inflammation. In the fibroblast culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblast cells caused by serum deprivation in a dose dependent manner up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study suggested that NO might act as a double-edged sword in ocular surface diseases depending on the degree of inflammation related with NO concentration.

Animals↗

PubMedDate not supplied

Development and characterization of a rabbit corneal endothelial cell line.

PURPOSE: To develop a rabbit corneal endothelial cell line by transducing human papilloma virus (HPV) type 16 E6 and E7 oncogenes, and to characterize the inherent biological properties of the established cell line. METHODS: Primary rabbit corneal endothelial cells were infected with a recombinant retrovirus harboring HPV E6 and E7, and the transformed cells were clonally selected by G418. RESULTS: Among the total of eight independent clones, one cell line (Clone no. A3) cultured over 40 passages was chosen to further characterize its inherent biological properties. Typical cell doubling time for these cells was 51 h, and the mean cell density of a flask culture was 1140 cells/mm(2). The various genes that are important for corneal endothelial functions were expressed at a level comparable to that of their normal counterparts. Furthermore, Na(+)/K(+) ATPase activity was maintained throughout an extended period, and the measured value at passage 30 was about 10 nmol inorganic phosphate/mg protein per minute. CONCLUSIONS: These results suggest that the rabbit corneal endothelial cell lines obtained here maintain normal corneal endothelial characteristics, and could be used not only for biological studies on corneal endothelial cells but also for such applications as the reconstruction of the ocular surface with an artificial cornea.

Animals↗

PubMedDate not supplied

Bone marrow-derived cells are present in Mooren's ulcer.

To investigate whether bone marrow-derived cells are present in Mooren's ulcer and involved in its destructive and regenerative disease course, tissue specimens were collected from 3 eyes of 3 patients with Mooren's ulcer that underwent lamellar keratectomy. Three normal donor limbal corneoscleras served as controls. Immunohistochemical staining patterns were analyzed by using the following antibodies: CD34 (a marker of hematopoietic progenitor cells and endothelium), c-kit (a marker of hematopoietic and stromal progenitor cells) and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhematopoietic progenitor cells). Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stromal cells were seen in normal limbal cornea, but no immunoreactivity for c-kit and STRO-1 was found. Bone marrow-derived cells are present in Mooren's ulcer and contribute to its destructive and regeneration process by synergizing with other factors. Specific therapeutic strategies that target the role of these cells in Mooren's ulcer are anticipated.

Antigens, CD34↗