초록 ▼

<1세부>
1)선별검사자료를 이용하여 유병율을 효율적으로 추정하기 위한 통계학적 방법을 제안
2)선별검사자료와 병원 자료를 연계하여 백내장 및 망막질환의 위험인자를 밝히고 위험 예측모형 제시
<2세부>
3)수정체상피세포는 TGF-$\beta$에 의해 세포고사가 일어난다.
4)수정체상피세포는 steroid나 산화스트레스에 의해 fibronectin이 증가한다.
5)수정체상피세포에서 JAK/STAT 신호전달 경로를 차단하면 세포사멸이 억제된다.
<3세부

<1세부>
1)선별검사자료를 이용하여 유병율을 효율적으로 추정하기 위한 통계학적 방법을 제안
2)선별검사자료와 병원 자료를 연계하여 백내장 및 망막질환의 위험인자를 밝히고 위험 예측모형 제시
<2세부>
3)수정체상피세포는 TGF-$\beta$에 의해 세포고사가 일어난다.
4)수정체상피세포는 steroid나 산화스트레스에 의해 fibronectin이 증가한다.
5)수정체상피세포에서 JAK/STAT 신호전달 경로를 차단하면 세포사멸이 억제된다.
<3세부>
6)자외선 조사 후 수정체 상피 세포 손상의 기전에는 NF-kB가 관여한다.
7)NF-kB의 활성을 억제시켰을 경우 수정체상피세포 손상이 억제된다.
<4세부>
8)산화스트레스를 이용한 백내장 유발 모델 설정
9)인삼추출물의 항백내장 효과 입증
<5세부>
10)배양망막세포에서 insulin의 투여로 산화스트레스와 VEGF를 유도함을 증명
11)riluzole이 인슐린에 의한 망막 세포에서의 VEGF 발현을 억제함을 증명
<6세부>
12)연령관련황반변성과 당뇨망막병증의 시험관 실험 모델과 동물 모델 확립
13)항산화제의 효능을 검증 새로운 치료방법의 가능성 제시

Abstract ▼

1. Study purpose and necessity
Due to advancement in medicine and improved income status, elderly population is steadily increasing. Cataract and retinal disorder are closely related to involutional changes. Western eating habits and increased prevalence in diabetes mellitus are also contributing

1. Study purpose and necessity
Due to advancement in medicine and improved income status, elderly population is steadily increasing. Cataract and retinal disorder are closely related to involutional changes. Western eating habits and increased prevalence in diabetes mellitus are also contributing factors for cataract and retinal disorder, but we do not even have a reliable data for disease frequency, yet. Prevalence, risk factors and statistical model for risk stratification are thus necessary to better understand diseases and benefit society. As for cataract, due to its nature of slow development, mechanism behind pathology has not been established with consensus yet. Retinal disorders are associated with systemic diseases such as diabetes mellitus, UV light, hormonal disturbance, or smoking, but no clear mechanism has been suggested, let alone proper treatment modality. This study attempted to verify the causative agents for cataract and retinal disorder in Korean, by combined works of clinical data and statistics
2. Study contents and extent
For first year, prevalence of cataract and retinal disorder was estimated from screening test and hospital data (1st subdepartment). Changes in ECM on lens induced by steroid use (2nd subdepartment), extent of cellular damage from UV exposure (3rd subdepartment), establishment of model for lens epithelial cells by oxidative stress (4th subdepartment), signal transduction in VEGF pathway induced by insulin on retinal cells (5th subdepartment), and development of model for aged cultured retinal pigment epithelial cells and quantitative analysis of apoptosis in oxidative stage in retinal nerve cell layer (6th subdepartment) were included. In second year, clarification of causative factors for cataract and statistical model for risk stratification (1st), study of evident changes in ECM proteins induced by steroid on lens epithelial cells (2nd), gene activation through cytokine activities in apoptosis (3rd), establishment of animal model for cataract and effects of saponin were examinated (4th). As for retinal study, effects of PCK inhibitor such as riluzole on VEGF pathway, induced by insulin in retinal cells (5th) and apoptotic activity of free radicals from vit C, or saponin on aged retinal pigment epithelial cells were studied for possible application in cataract treatment (6th). In 3rd year, development of total system for analysis and estimation of risk for cataract and retinal disorders (1st), fibrosis and changes in protein on lens epithelial cells after treatment with steroid and $H_2O_2$ (2nd), changes in composition of amino acid from UV light exposure on cultured lens cells (3rd), and basic study for development of eyedrops (4th) were interconnected. In retinal disorders, effects of VEGF on epithelial cell growth in retinal vessels, the pathway for signal transduction, and possible measure for prevention (5th) and treatment of study animals with induced macular degeneration with anti-oxidative agents and ginseng were carried out (6th). In fourth year, correction and addition of cataract risk stratification system (1st), detailed study on oxydative damage in lens epithelial cells (2nd) were done. Changes in animal (Spraue-Dawley rat) from UV light exposure and exploration of possible materials that either promote or prevent damage (3rd), preparation for development of eye drops with saponin(4th) were done. In vivo model in retinopathy of premature babies was applied to evaluate the effects of PKC inhibitor such as riluzole (5th), and effects of antioxidants and YC-1 on animal models with retinal degeneration was studied(6th).
3. Study results
In 1st subdepartment, estimation in prevalence of cataract patients from statistical model In our study was not significantly different from previously reported studies. Risk factors were searched from surveying and hospital data and estimation model for disease occurrence was created. 2nd subdepartment revealed TGF-beta as inducible agent of apoptosis in lens epithelial cells, and showed steroid or oxydative stress ($H_2O_2$) can cause changes in ECM, especially in fibronectin. This mechanism is also important in JAK/STAT signal pathway When JAK/STAT pathway is blocked, apoptosis was observed in amniotic membrane conditioned media. In 3rd subdepartment, in vitro and in vivo studies confirmed the effect of NF-kB on cellular damage of UV-exposed lens epithelial cells. In 4th subdepartment, anti-cataract effects of ginseng extract was studied and development of eyedrops was attempted. 5th subdepartment showed that administration of insulin induced VEGF on cultured cells and animal model, which was suppressed by riluzole. In 6th subdepartment, in vivo and in vitro model of age related macular degeneration and diabetic retinopathy was established and effects of various anti-oxidants were elucidated.
4. Application of study results
Estimated prevalence of cataract can be used as a guideline for various epidemiological and domestic affairs and may benefit patients in managing their preventable risks and reducing changes of progression into cataract or retinal disorders. On macroscopic view, proper treatment according to risk stratification would help lower the national medical budget. In cataract study, mechanism of steroid induced cataract was well explained with our model, and signal transduction in apoptosis after oxidative stress was examined in depth. Involvement of NF-kB in cataract formation has been discovered for the first time in our study. We were unable to develop new eyedrops due to technical difficulties, but have come up with the detailed model and problems associated with development of new medication. In retinal study, animal model of age related macular degeneration and diabetic retinopathy was established and laid ground for future development of newt medication using riluzole. Anti-oxidant such as vitamin E or ginseng extract was found helpful for age related macular degeneration, and study of YC-1 confirmed its candidacy for development of new medication. Vitamin B6 was found promising in protection of retina in diabetic patients. Stellate ganglion block suggested its possiblity as an alternative method of treatment in ischemic retinopathy.

목차 Contents

• 제 1 장 연구개발과제의 개요...122
• 제 2 장 국내외 기술개발 현황...127
• 제 3 장 연구개발수행 내용 및 결과...128
• 제 4 장 목표달성도 및 관련분야에의 기여도...148
• 제 5 장 연구개발결과의 활용계획...152
• 제 6 장 연구개발과정에서 수집한 해외과학기술정보...152
• 제 7 장 참고문헌...153
• 제 8 장 첨부서류...155