Activation of Protein Tyrosine Kinase Pathway in Diabetic Rats.

Kim, Hyung Chan

Original Article

Journal of the Korean Ophthalmological Society 1998;39(5):939-948.
Published online May 1, 1998.

Activation of Protein Tyrosine Kinase Pathway in Diabetic Rats.

Hyung Chan Kim

Department of Ophthalmology, College of Medicine, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Korea.

당뇨쥐에서 Protein Tyrosine Kinase Pathway 의 활성화

김형찬(Hyung Chan Kim)

Abstract

One mechanism of vascular damage in diabetic retinopathy is thought to result from the effect of hyperglycemia on the neural retina and microvasculature eventually causing the signs of capillary closure and clinical retinopathy. We reasoned that protein tyrosine kinase (PTK) pathways are abnormally activated in the retina prior to the onset of clinical changes. In this study, twelve Zucker diabetic fatty rats were compared with twelve male lean litter mates as control. The rats were examined for changes in the relative retinal levels of angiogenic growth factors, phosphotyrosine, PCNA, and tyrosine kinase pathway intermediates by western blot analysis. We found that the Zucker diabetic fatty rats have increased levels of the angiogenic growth factors, VEGF and PDGF. The levels of phosphotyrosine and PCNA, and phosphorylated intermediates, MAPK and PI3-K were also increased as compared with the lean control rats. These data indicate that the microvascular changes known to occur in this model are associated with elevation of VEGF and PDGF prior to the development of clinical apparent retinopathy. The elevations of VEGF and PDGF may explain in part the activation of the tyrosine kinase pathways, especially pathways that include MAPK and PI3K.

Key Words: Angiogenic growth factor;Diabetic rats;Microvascular retinopathy, ;Phosphotyrosine;Protein tyrosine kinase pathway