Retinitis Pigmentosa. a Canine Animal Model of Investigation

遺傳性視網膜變性疾病之犬模式研究

林中天(Chung-Tien Lin) ； 陳慕師(Muh-Shy Chen)

《中華民國眼科醫學會雜誌》 42卷2期 (2003/06) Pp. 101-109

https://doi.org/10.30048/ACTASOS.200306.0001

摘要

色素性視網膜炎為一嚴重而又常見的變性眼疾，為人類視網膜變性疾病中最常見的眼病。對動物模式的研究將有助於瞭解此重要的眼疾。於犬動物模式的視網膜變性疾病中最常見的為廣泛進行性視網膜退化(generalized progressive retinal atrophies)，此病相當於人類的色素性視網膜炎。本文作者於英國研究此疾病的分子生物學研究多年，將研究成果和國外報告做綜合性報告。
經多年研究成果，此廣泛進行性視網膜退化可能和操控4大類蛋白質的基因突變有關：(1)光傳導作用蛋白質，包括視蛋白、傳導素、cGMP磷酸二酯酶等；(2)感光細胞構造性蛋白質如周邊素；(3)視網膜色素上皮細胞感光細胞代謝作用相關之蛋白質；(4)功能仍未明之蛋白質。
分子遺傳學之研究有助於找到此類複雜成因的視網膜疾病之致病機轉。此外，以基因治療的方式來嘗試治療遺傳性視網膜退化也已在動物模式中進行，期望動物模式之研究有助於人類相似疾病病因之了解以及治療之突破。

並列摘要

Retinitis pigmentosa (RP) is a common degenerative retinal disorder in human. Canine model of retinal dystrophies represents a diverse group of naturally occurring models of inherited retinal dystrophies in dogs. Most of the canine retinal dystrophies are with importance in comparative medicine that offers animal models and candidate genes to further the understanding of retinal diseases in human. Among the canine retinal dystrophies, the most important group of diseases are the generalized progressive retinal atrophies (GPRAs) that affect more than one hundred different dog breeds. GPRA is the canine homologue of human RP, with which it shares similar phenotypes and pathology. Here we review recent research progress on the canine model of RP.
The potential candidate genes for retinal degenerations are classified into four areas based on the functions of their coding proteins: (1) phototransduction cascade proteins (rhodopsin, transducin, cGMP-PDE, cGMP-gated ion channel etc.); (2) photoreceptor structural proteins (peripherin/RDS and Rom-1 etc); (3) proteins associated with RPE-photoreceptor metabolism; (4) proteins with unknown functions.
Molecular investigation of candidate genes in animal models can yield new potential candidate genes for human diseases and even lead to the identification of disease causing genes. In addition, the therapeutic genetic approaches on experiment animals to restore or rescue visual functions are valuable to predict the success rate and safety of gene therapy trials performed in human at a later stage. Therefore, animal models are important research resources for understanding disease mechanism and therapeutic potential for human diseases.

並列關鍵字

retinal dystrophies ； retinal degeneration ； animal model ； dog