原発性開放隅角緑内障(広義)への挑戦:臨床的諸問題とその科学的解決

フォーマット:

論文

責任表示:

杉山, 和久

言語:

日本語

出版情報:

Japanese Ophthalmological Society = 日本眼科学会, 2012-03-01

著者名:

杉山, 和久  

掲載情報:

日本眼科学会雜誌 = Nippon Ganka Gakkai zasshi

ISSN:

0029-0203      

巻:

116

通号:

3

開始ページ:

233

終了ページ:

268

バージョン:

publisher

概要:

Primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG), is reported by the Tajimi Study to afflict 3.9% of the total population, and this represents about 80% of all total glaucoma cases which, in total, afflict 5.0% of the population. We tried to analyze the clinical problems relating to POAG by looking at the pathogenesis, intraocular pressure (IOP), therapy, neuroprotection and surgery of the disease. To elucidate the pathogenesis of … glaucoma progression, we measured retinal nerve fiber layer defect (RNFLD) angles', and divided the NTG cases into 2 groups, enlarged RNFLD and stable RNFLD. Disc hemorrhages were found to be significantly more frequent in the enlarged group than in the stable group. RNFLD was enlarged in the direction of disc hemorrhage in over 80% of the eyes. In the majority of the eyes of the enlarged group, the enlargement of RNFLD was toward the fovea. The enlargement of RNFLD in NTG was closely associated with disc hemorrhage and the deterioration of the visual field. We developed a simultaneous structure and function evaluation technique combining spectral-domain (SD) optical coherence tomography (OCT) and fundus-oriented perimeters for the detection of visual field abnormalities in the RNFLD area. We superimposed the ganglion cell complex map obtained by SD-OCT on the fundus-oriented perimeter image. We observed very early or preperimetric normal pressure glaucoma as well as disc hemorrhage adjacent to the borders of the RNFLD. The borderline of the RNFLD seemed to be the thinnest RNFL and had the lowest retinal sensitivity (Active site for RNFLD progression). To clarify the role of the circadian clock genes in the generation of a 24-hour IOP rhythm, we used the microneedle method to measure the IOP at eight time points daily, both in wild type mice and Cry-deficient (Cry 1-/-Cry 2-/-) mice. In the wild-type mice living in light-dark conditions, the pressure measured in the light phase was significantly lower than in the dark phase. This biphasic daily rhythm was maintained under dark-dark conditions. In contrast, the Cry-deficient mice did not show significant circadian changes in their IOP, regardless of the environmental light conditions. These findings demonstrate that clock genes are essential for the generation of the circadian rhythm of IOP. We evaluated the relationship between the genetic polymorphisms of the adrenergic receptor (ADR) and the diurnal IOP in untreated NTG patients. For Del 301-303 in α2B-ADR, De1322-325 in α2C-ADR, and S 49G (A/G) in βl-ADR, the major homozygotes and minor carriers had parallel diurnal IOP curves, but significantly different diurnal IOP levels. Polymorphisms of the ADR gene may predict the diurnal IOP level of patients with NTG. Looking toward the future, tailor-made medicine in glaucoma therapy, we evaluated the relationship between the polymorphisms of the prostaglandin F2α, receptor (FP receptor) gene and the effectiveness of topical latanoprost treatment in 100 normal volunteers. One SNP(rs3753380) was located in the promoter region of the FP receptor gene and was significantly correlated with % IOP reduction. 続きを見る

URL:

http://hdl.handle.net/2297/32485