Genetic approach in Japanese patients with retinitis pigmentosa

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 04454437
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: CHIBA UNIVERSITY
• Principal Investigator: ADACHI Emiko Chiba University School of Medicine Professor, 医学部, 教授 (60009496)
• Co-Investigator(Kenkyū-buntansha): TSUYAMA Yoshihiko Chiba University School of Medicine Assistant, 医学部, 助手 (50210571) ; UEDA Masahiro Chiba University School of Medicine Assistant, 医学部, 助手 (70193810) ; MURAYAMA Koichiro Chiba University School of Medicine Associate Professor, 医学部, 講師 (00219891) ; KAN-NO Masamoto Chiba University School of Medicine Associate Professor, 医学部, 助教授 (40161393) ; KIMURA Tsuyoshi Chiba University School of Medicine Associate Professor, 医学部, 助教授 (80003391)
• Project Period (FY): 1992 – 1994
• Keywords: Rhodopsin-gene / Retinitis pigmentosa / Peripherin-gene / Electroretinogram / Gene analysis / Fluorescein angiography / Sodium iodide

Research Abstract

We performed firstly the analysis of the rhodopsin gene from patients with a form of autosoma dominant retinitis pigmentosa. Since the rhodopsin-gene has 5 exons, each of them was separately amplified with the use of a PCR method and DNA sequence determination was done. In order to study a number of patients, screening study was done with a SSCP method as well as a PCR method Besides, sequential method was used to obtain more secure informations.
We found some polymorphic changes of the gene near the exon of the rhodopsin gene. However the families we investigated showed no mutation on the rhodopsin gene which linked to the disease. Then, we studied four exons of the peripherin-gene with a SSCP method and could not fined the abnormality in electrophoresis. We are still going on to do the same analysis in other families with autosomal dominant retinitis pigmentosa*. On the other hand, classification of retinitis pigmentosa based on clinical features let the gene analysis of these patient s easier and be helpful, especially in cases whose heredities are unknown. Together with subjective symptoms such as dark adaptation visual fields, visual acuities and fundus appearance with the aid of fluorescein angiography electrophysiological study was expected to give further precious information of the disease.
In order to know the pathological and physiological changes of the retina with pigmentary degeneration, we made experimentally retinal pigmentary degeneration in mice by injecting sodiun*iodide. The retina was electrophysiologically (electroretinogram) and electron-microscopically studied under several conditions such as light-damaged, toxically invaded and others. Besides, the neuro*transmitter-activities, especially glutamates of the retina was studied combining immunochemica approaches.
The results obtained from the experimentally induced retina showed functional and histopathologica* abnormalities which will provide to understand the unclarified abnormal function of retiniti*pigmentosa.