The role of polyol pathway in high glucose-induced apoptosis of retinal pericytes and proliferation of endothelial cells

¹ Ophthalmology, University of Fukui, 23-3 Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
² Ophthalmology, University of Fukui, Fukui, Japan

^* To whom correspondence should be addressed. E-mail: ytakamura{at}hotmail.com.

	Abstract

Purpose; Selective degeneration of pericytes and proliferation of endothelial cells (ECs) appear to be associated with microaneurysm formation, an initial deficit in the early stage of diabetic retinopathy. We investigated the preventive effect of aldose reductase (AR) inhibitor for high-glucose-induced pericyte loss and EC growth. Methods; Using an in vitro coculture system to mimic the interaction between pericytes and ECs, we examined the effect of high-glucose (30 mM) exposure in the presence or absence of ARI for the cell growth of porcine pericytes and ECs. To know the role of transforming growth factor-(TGF-), its amount in culture media was measured, and the effects of the treatment of TGF-or neutralizing antibody for EC growth were examined. Results; Abundant expression of AR and increased levels of polyol and apoptosis induced by high glucose were observed in pericytes, but not in ECs. ECs over-expressing AR cultured in high-glucose medium showed decreased cell viability. The growth-inhibitory effect of ECs upon co-culture with pericytes was attenuated by exposure to a high glucose concentration. Biochemical assays disclosed that the levels of active TGF- in media were linked to EC growth. Supply of active TGF- to co-culture medium containing 30 mM D-glucose restored the inhibitory activity on EC growth. Conclusions; AR inhibitor rescued pericytes from high-glucose-induced apoptosis and maintained the levels of TGF-, resulting in the prevention of co-cultured EC growth.

Key Words: aldose reductase, apoptosis, diabetic retinopathy, polyol pathway, retinal pericytes