Studies on pathogenesis of retinal dystrophy
| Project/Area Number |
59440074
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Kyoto University |
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Principal Investigator |
塚原 勇 京都大学, 医学部, 教授
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| Project Period (FY) |
1984 – 1985
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| Project Status |
Completed (Fiscal Year 1985)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1985: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1984: ¥13,000,000 (Direct Cost: ¥13,000,000)
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| Keywords | retinal dystrophy / chloroquine / phenothiazines / retinal drusen / prostaglandin <D_2> synthetase / adenyl cyclase / guanyl cyclase / 網膜色素上皮細胞 |
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| Research Abstract |
Pathogenesis of human retinal dystrophy is not yet elucidated, while its clinical features have been well described. Thus We studied on several experimental retinal dystrophies and on some enzymes of the retinal pigment opithelium of which dysfunction lead the retina to dystrophy.
1) Administration of chloroquine in a albino tropical fish, colydoras, induced retinopathy. Membraneous inclusion bodies appeared first in ganglion cells, amacrine cells and horizontal cells, but did not destroyed their cellular integrity. Inclusion bodies were then observed in photoreceptor cells which got cellular destruction. Retinal pigment epithelial cells showed only a minimal change even at the end stage. These results clarified the direct damage of photoreceptors in chloroquine retinopathy.
2) Phenothiazines induced a specific structural changes, elongation with narrowing and honey-comb figures, in microvilli of retinal pigment epithelial cells, and profoundly decreased phagocytic activity. Simillar cha
… More
nges occured with calmodulin antagonists and cytochalasin B. Retinal degeneration may be caused by destruction of actin of actin filaments in phenothiazine retinopathy.
3) Double layered cultured chick retinal pigment epithelial cells phagocytosed latex particles from apical side and exocytosed particles from basal side of the upper cells. Exocytosed particles were phgocytosed again by lower cells. We observed basal cell membrane opening just at the exocytosing. This suggested the pathogenesis of retinal drusen.
4) Chick retinal pigment epithelial cells showed a high activity of glutathione-requiring prostaglandin <D_2> synthetase, while neural retina had no detactable activity. Prostaglandin <D_2> was a specific prostaglandin to reverse the inhibitory effect of cyclic AMP on the phagocytic activity of retinal pigment epithelial cells. These suggested a possible participation of prostaglandin <D_2> in in vivo function of retinal pigment epithelium.
5) Adenyl cyclase and guanyl cyclase activity were proved to be localized at microvilli membrane of retinal pigment epithelial cells in rat. This corresponded very well with our hypothesis that phagocytic activity of retinal pigment epithelial cells is regurated by cyclic AMP and cyclic GMP in the Yin-Yang manner Less
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Report
(1 results)
Research Products
(10 results)
