초록 ▼

1. 아벨리노각막영양증 동형접합자를 21명 찾아냈고, Hardy-Weinberg 공식을 통하여 국내 이형접합자의 빈도가 1,000명당 1명임을 발견함.
2. 라식수술 후 악화된 각막에서 각막절편을 채취한 뒤 bigh3 단백질의 항체를 이용하여 광학현미경하 면역조직학적 염색을 시행하여 침착물질이 bigh3 단백질임을 밝힘.
3. 라식수술 후 악화된 각막에서 각막절편을 채취하여 혈액성분과 접촉시켜 침착물질이 용해됨을 관찰하여 침착물질의 용해 가능성을 발견함.
4. 아벨리노 각막이영양증 환자에서 각막신생혈관이 존재할 경우

1. 아벨리노각막영양증 동형접합자를 21명 찾아냈고, Hardy-Weinberg 공식을 통하여 국내 이형접합자의 빈도가 1,000명당 1명임을 발견함.
2. 라식수술 후 악화된 각막에서 각막절편을 채취한 뒤 bigh3 단백질의 항체를 이용하여 광학현미경하 면역조직학적 염색을 시행하여 침착물질이 bigh3 단백질임을 밝힘.
3. 라식수술 후 악화된 각막에서 각막절편을 채취하여 혈액성분과 접촉시켜 침착물질이 용해됨을 관찰하여 침착물질의 용해 가능성을 발견함.
4. 아벨리노 각막이영양증 환자에서 각막신생혈관이 존재할 경우 신생혈관주위로 각막혼탁이 없음을 밝히고, 이를 통해 아벨리노 각막이영양증의 각막내 혈관 도입법을 만듦.
5. 병인이 이상단백질의 세포외로의 배출이상으로 의심되는 바 세포연구를 통해 이상단백질의 배출 이상부위를 찾고 있으며, secretory vesicle에서 그 이상소견을 발견함.
6. 각막손상물질인 자외선이 TGF-beta를 증산시키고 그로 인해 bigh3 단백질이 증산됨을 발견함.
7. 감소된 cysteine cathepsin의 발현은 각막이영양증 환자 각막의 세포외 기질구성과 조성에 영향을 미쳐 bigh3 단백질이 세포외 기질에 침착하는데 기여함을 밝힘.

Abstract ▼

I. Study purpose and necessity
Avellino corneal dystrophy is an autosomal dominant dystrophy with clinical features of both granular and lattice stromal deposits. It progresses with age starting from anterior granular stromal deposits to the mid-stromal haze and causes severe visual loss especial

I. Study purpose and necessity
Avellino corneal dystrophy is an autosomal dominant dystrophy with clinical features of both granular and lattice stromal deposits. It progresses with age starting from anterior granular stromal deposits to the mid-stromal haze and causes severe visual loss especially in homozygotes. In the heterozygote, the corneal deposits are known to increase after surgical intervention such as laser in situ keratomileusis(LASIK). The incidence of Avellino corneal dystrophy in South Korea is approximately 1/1,000, adding up to about 40,000 heterozygotes in South Korea alone. This study attempt to verify the causative agents for Avellino corneal dystrophy and shed light on new treatment modalities on Avellino corneal dystrophy so as to prevent any more visual loss of Avellino corneal dystrophy patients and even help to recover from corneal haze.
II. Study contents and extent
1. Study contents
1) Based on the hypothesis that the main composition of corneal lesions(deposits) is clusters of abnormal protein-bigh3 protein, the relationship between Granular, Reis-Bucklers` and Lattice corneal dystrophy was studied.
2) The mechanism of dissolution by blood was proved and the efficacy of serum eyedrops was evaluated.
3) The effect of the technique that introduced a vasculature onto the cornea by means of a conjunctival advancement flap was evaluated.
4) On the theory that the corneal lesions are due to trafficing-defected extracellular secretions of an abnormal protein, the precise localization of the abnormal secretion was studied.
5) A method to determine the intracellular location of where the bigh3 protein degradation occurred was found. Also, attempts were made to find a way to increase the degradation rate of the abnormal protein.
6) The mechanism of intracellular signal transduction of TGF-beta was investigated, so as to devise a method to inhibit the process.
2. Study extent
1) Persistent diagnosis of Avellino corneal dystrophy through genetic screening.
2) Persistent and further study on the material that causes dissolution of abnormal proteins.
3) Localization of trafficing under confocal microscopy through transfection of abnormal protein gene into the normal keratocyte.
4) Study on the signaling of TGF-beta that has essential role in producing abnormal proteins.
III. Study Results
1. The Avellino corneal dystrophy gene for homozygotes was found. Using the Hardy-Weinberg formula, it was estimated that at least 1 in 1,000 of the population of South Korea are heterozygotes.
2. Corneal flaps from exacerbated patients after LASIK were studied and the stromal deposits were confirmed to be the bigh3 protein.
3. The abnormal protein deposits were partially disscolved after contact with serum.
4. The absence of stromal haze near neovascularization in Avellino corneal dystrophy, led to the hypothesis that introduction of vasculature onto the cornea could be a part of treatment modalities.
5. Presumed pathogenesis of Avellino corneal dystrophy lies with the abnormal secretion of abnormal proteins, and attempts were made at localization of the defective pathway.
6. Ultraviolet light was found to upregulate TGF-beta, and a subsequent increase in bigh3 protein was detected.
7. A decrease in cysteine cathepsin expression, results in extracellular matrix modulation, paving the way for bigh3 protein deposition on the corneal stroma.
VI. Application of study results
1. Prevention of visual loss through education of the general public.
2. Pharmaceutical possibilities through serum investigation.
3. Possibly investigate therapeutic modalities for other corneal dystrophies sharing the bigh3 gene anomaly.
4. Possibly investigate therapeutic modalities for other storage type disorders.
5. Possible patents for new diagnostic and therapeutic modalities.
6. Associated investigation with TAEJUN pharmaceuticals Ltd,. Inc. into developing a topical ophthalmic solution.

목차 Contents

• 표지...1
• 제출문...2
• I. 총괄현황...3
• 목차...4
• 보고서 요약서...5
• 요약문...6
• SUMMARY...8
• 연구 성과 실적 및 향후 계획...10
• II. 총괄연구과제 연구결과...33
• 1. 연구개발과제의 배경 및 필요성...34
• 2. 국내외 기술개발 현황...42
• 3. 연구개발과제의 추진체계...43
• 4. 연구개발수행 내용 및 결과...44
• 4.1. 연구회 운영실적...48
• 5. 목표달성도 및 관련분야 기여도...49
• 5.1. 총괄연구개발과제의 목표달성도...49
• 5.2. 관련분야 기여도...52
• 6. 향후 연구성과 추진 계획...53
• 7. 연구개발결과 추진 계획...53
• 7.1. 기술적 파급효과...53
• 7.2. 경제.산업적 파급효과...53
• 7.3. 사회적 파급효과...53
• 8. 연구개발결과의 활용계획...54
• 8.1. 연구개발결과의 활용계획 및 추가연구의 필요성...54
• 8.2. 사업화(기업화) 목표 달성도 및 계획...54
• 8.3. 사업화 수준(계획 및 완료 포함)...54
• 9. 연구개발과정에서 수집한 해외과학기술정보...54
• 10. 참고문헌...55
• III. 첨부서류...58
• 자체평가의견서...59
• 연구성과 실적 증빙서류...63